Correlation between urinary cadmium concentrations and hospital mortality in acute respiratory distress syndrome: a prospective observational cohort study

Correlation between urinary cadmium concentrations and hospital mortality in acute respiratory distress syndrome: a prospective observational cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Correlation between urinary cadmium concentrations and hospital mortality in acute respiratory distress syndrome: a prospective observational cohort study Li-Chung Chiu, Hsin-Hsien Li, How-Wen Ko, Ping-Chih Hsu, Chung-Shu Lee, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9086457/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 22 You are reading this latest preprint version Abstract Background Cadmium and nickel exposure has been shown to induce oxidative stress, exacerbate inflammation, and trigger immunotoxicity—all of which may play central role in the pathophysiology of acute respiratory distress syndrome (ARDS). This study investigated association between cadmium and nickel exposures and the severity of ARDS. Methods This prospective observational study enrolled critically ill patients with or without ARDS who had been admitted to an intensive care unit (ICU) in Taiwan between November 2021 and April 2025. Clinical outcomes were compared with cadmium and nickel concentrations in blood and urine, measured within 3 days after ARDS onset (ARDS patients) or within 3 days after ICU admission (control subjects). Results A total of 181 patients with ARDS and 49 ICU control subjects were included. The overall in-hospital mortality rate of ARDS patients was 43.1%. Urinary cadmium concentrations were significantly higher in ARDS patients than in ICU control patients. Among ARDS patients, non-survivors had significantly higher urinary cadmium/creatinine values, higher neutrophil/lymphocyte ratios, and a higher risk of organ failure (i.e., higher APACHE II and SOFA scores) (all p 4.55 µg/g; 105 patients; 58%) faced a significantly higher risk of organ failure (i.e., higher SOFA scores), interleukin-6 values, risk of hypoxemia (i.e., lower PaO 2 /FiO 2 ), and 28-, 60-, 90-day, and all-cause hospital mortality, compared to those with low of urinary cadmium/creatinine values (≤ 4.55 µg/g; 76 patients; 42%) (all p < 0.05). Multivariable logistic regression models revealed that urinary cadmium/creatinine levels were independently associated with hospital mortality (adjusted OR 1.031 [95% CI 1.001–1.062], p = 0.045), and that a urinary cadmium/creatinine value > 4.55 µg/g had the greatest predictive value (adjusted OR 2.365, [95% CI 1.003–5.578], p = 0.049). Conclusions Elevated urinary cadmium concentration in the early course of ARDS is independently associated with increased hospital mortality. Clinical trial number: not applicable. Cadmium Nickel Acute respiratory distress syndrome Oxidative stress Outcomes Mortality Figures Figure 1 Figure 2 Background Acute respiratory distress syndrome (ARDS) is a potentially lethal form of acute respiratory failure characterized by profound hypoxemia resulting from pulmonary or extrapulmonary clinical insult. The condition contributes to multiple organ failure and increases the risk of mortality. Current ARDS management strategies focus mainly on lung-protective ventilation strategies and lack specific pharmacological therapies [ 1 – 3 ]. Reducing morbidity and mortality among critically ill patients requires a clear understanding of all risk factors that predispose patients to ARDS onset and progression. Heavy metal pollutants pose a considerable threat to public health, due to their adverse effects on inflammation, oxidative stress, mitochondrial dysfunction, and overall organ health. Numerous environmental pollutants have been linked to disruption of the alveolar capillary barrier, recruitment of inflammatory cells, excessive cytokine release, and endothelial injury—factors that increase lung vulnerability to ARDS in patients such as pneumonia or sepsis [ 4 – 7 ]. The main routes of heavy metal exposure are airborne pollutants, occupational exposure, contaminated drinking water and diet, tobacco, and dermal contact. Heavy metal toxicity depends on the inherent properties of the metal, the degree of bioaccumulation, and the exposure dose, route, and frequency. Heavy metal exposure has been shown to disrupt cellular redox homeostasis by reducing antioxidant levels, provoking excessive reactive oxygen species (ROS) production and oxidative stress, impairing the mitochondrial electron transport chain, and inducing stress in the endoplasmic reticulum, collectively contributing to apoptosis, endothelial cell injury, tissue damage, airway inflammation, ultimately leading to organ dysfunction [ 4 , 8 , 9 ]. Cadmium and nickel are both recognized as heavy metal toxicants and carcinogens. Cadmium is a cumulative toxin with a relatively long half-life of 6 to 38 years, whereas nickel is a non-cumulative toxin with a half-life of 17 to 53 hours. Cadmium and nickel are predominantly excreted through urine. Urinary cadmium levels are considered surrogates of chronic exposure and total body burden, whereas urinary nickel concentrations are more indicative of recent acute exposure [ 10 – 13 ]. Exposure to cadmium or nickel has been identified as a risk factor for increased susceptibility to various infectious respiratory diseases, including coronavirus disease 2019 (COVID-19). Previous studies have reported possible links between cadmium or nickel exposure and COVID-19 severity and clinical outcomes [ 14 – 17 ]. ARDS pathophysiology is characterized by oxidative stress, dysregulated airway and systemic inflammatory cascades, and immune cell activation [ 18 – 20 ]. However, the potential impact of cadmium and nickel exposure on the development, severity, and clinical outcomes of ARDS remains unclear. This study investigated the potential association between cadmium and nickel exposures and clinical outcomes in patients with ARDS. Methods Study design and patients This prospective study enrolled patients who had been admitted to the intensive care unit (ICU) of a Taiwanese tertiary care referral center (Chang Gung Memorial Hospital, Linkou branch) between November 2021 and April 2025. Blood and urinary cadmium and nickel concentrations were collected within 3 days of the ARDS onset (ARDS patients) or ICU admission (control subjects). Bronchoalveolar lavage (BAL) was performed within one week of ARDS onset for pathogen identification in selected cases identified by the attending intensivist. ARDS was defined in accordance with the Berlin criteria [ 21 ]. The exclusion criteria included (1) age < 20 years, (2) end-stage renal disease requiring maintenance dialysis, (3) acute kidney injury with oliguria, (4) mortality within 7 days after ARDS onset or after ICU admission (5) a history of residing in a cadmium or nickel contaminated area or working in a cadmium or nickel emitting industry (6) inability to obtain informed consent from patients or their legal representative. This study was conducted in accordance with the Declaration of Helsinki, and approval was obtained from the Institutional Review Board of CGMH for Human Research (CGMH IRB No. 202100595A3, 202201833A3, and 202300897A3). Data collection Demographic data, smoking status, underlying comorbidities, and the etiology of ARDS were recorded for all participants. Blood and urinary cadmium and nickel concentrations as well as interleukin-6 (IL-6) levels were measured within 3 days of enrollment. Other clinical and laboratory variables including Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score were collected at days 1, 3, and 7 after ARDS onset (ARDS patients) or at days 1, 3, and 7 after ICU admission (control subjects). Additional recorded variable included dates of hospital and ICU admission, the presence of shock, the use of inotropic agents, renal replacement therapy, ARDS onset, mechanical ventilator initiation and liberation, ICU and hospital discharge, and time of death. Outcome measurements Primary outcomes were 28-day, 60-day, 90-day, and all-cause hospital mortality. Secondary outcomes included use of inotropic agents, incidence of shock, occurrence of acute kidney injury (with or without renal replacement therapy), duration of mechanical ventilation, length of ICU stay, and length of hospital stay. Hospital mortality was defined as death from any cause during the hospital stay. Survivors were defined as patients alive 90 days after hospital discharge. Measuring cadmium and nickel levels in blood and urine, and cadmium concentrations in bronchoalveolar lavage Blood specimens were collected in 6 mL plastic blood collection tubes containing K2EDTA as an anticoagulant (BD, Franklin Lakes, NJ, USA). Urine and BAL specimens were collected in 10 mL metal-free plastic collection tubes. All blood, urine and BAL specimens were stored at 4°C, prior to cadmium and nickel measurements conducted using inductively coupled plasma mass spectrometry. The relevant details pertaining to the methods used for the cadmium and nickel measurements are provided in Supplementary File 1. Statistical analysis Continuous variables were expressed as mean ± standard deviation for normally distributed data, or as median and interquartile range for non-normally distributed data. A student’s t-test or the Mann–Whitney U test was used to compare continuous variables between groups. Categorical variables were presented as counts and percentages, and comparisons were made using the chi-square test for equal proportions or Fisher’s exact test, as appropriate. Receiver operating characteristic curves were used to evaluate the value of variables in predicting the hospital mortality of ARDS patients. The Youden index was used to determine cutoff values to dichotomize continuous variables, categorizing ARDS patients into high or low urinary cadmium groups. Univariable analysis was first performed to identify risk factors associated with hospital mortality in ARDS patients, followed by the construction of multivariable logistic regression models using stepwise selection to adjust for potential confounding factors. The results were reported using odds ratio (OR) and 95% confidence interval (CI). Cumulative probabilities of hospital survival for each group were generated as a function of time using the Kaplan–Meier method and compared using the log-rank test. All statistical analyses were conducted using SPSS version 29.0 (IBM Inc., Armonk, NY), and a two-sided p value < 0.05 was considered statistically significant. Results From a total of 4517 patients admitted to ICU during the study period, 181 patients with ARDS and 49 patients without ARDS were included in the final analysis (Fig. 1 ). The overall all-cause hospital mortality among ARDS patients was 43.1%. Comparison of ARDS patients and ICU control patients without ARDS As shown in Table 1 , no significant difference in age or gender distribution was detected between the ARDS and ICU control groups. Mean body mass index (BMI) was significantly higher in the ARDS group than in the ICU control group. More than half of the patients enrolled in the study were never-smokers, and no significant difference in smoking history (current or former) was observed between the two groups. Comorbidity profiles were similar, except for a higher prevalence of chronic lung disease in the control group. APACHE II and SOFA scores were significantly higher in the ARDS group than in the ICU control group (both p < 0.05). The detected values of inflammatory markers, such as neutrophil to lymphocyte ratio, C-reactive protein (CRP), and IL-6 were significantly higher in the ARDS group (all p < 0.05). Table 1 Baseline characteristics and clinical variables of ICU controls versus ARDS patients Variables ICU controls ARDS patients p value ( n = 49) ( n = 181) Age (years) 61.6 ± 14.5 64.3 ± 13.3 0.224 Male (gender) 30 (61.2%) 135 (74.6%) 0.065 Body mass index (kg/m 2 ) 21.7 ± 4.5 24.1 ± 4.6 0.001 Smoking history 0.819 Current smoker 10 (20.4%) 41 (22.7%) Former smoker 10 (20.4%) 42 (23.2%) Never smoked 29 (59.2%) 98 (54.1%) Hypertension 18 (36.7%) 88 (48.6%) 0.139 Diabetes mellitus 21 (42.9%) 62 (34.3%) 0.266 Chronic heart disease 6 (12.2%) 24 (13.3%) 0.852 Chronic lung disease 19 (38.8%) 37 (20.4%) 0.008 Chronic liver disease 9 (18.4%) 18 (9.9%) 0.104 Chronic kidney disease 3 (6.1%) 29 (16%) 0.102 Immunocompromised status 22 (44.9%) 84 (46.4%) 0.851 APACHE II score 13.5 ± 5.2 16.6 ± 7.1 0.001 SOFA score 3.7 ± 3.3 8.7 ± 3.8 < 0.001 WBC (10 3 /µL) 12 ± 5.7 11.1 ± 6.9 0.390 Neutrophil (%) 82.8 (77.5–90.2) 87.5 (80.4–92.4) 0.372 Lymphocyte (%) 8.7 (4.5–13.5) 5.8 (2.9–9.5) 0.017 Neutrophil/lymphocyte ratio 8.7 (5.7–17.7) 15.2 (8.2–30.5) < 0.001 Hemoglobin (g/dL) 10.7 ± 2.4 9.9 ± 2.1 0.025 Platelets (10 3 /µL) 225.6 ± 115.4 166.6 ± 107.8 0.001 Serum creatinine (mg/dL) 0.7 (0.5–1.2) 1.0 (0.5–2.0) 0.001 Bilirubin (total) (mg/dL) 0.6 (0.3–0.9) 0.5 (0.3–0.7) 0.680 Lactate (mg/dL) 10.5 (7–14.2) 12.6 (9.6–19.1) 0.029 CRP (mg/L) 72 (22.3–124.7) 127 (54.8–193.3) 0.002 IL-6 (pg/mL) a 18 (4.8–47.8) 35.4 (12.2–163) 0.002 Blood cadmium (µg/L) 0.7 ± 0.4 0.8 ± 0.5 0.349 Blood nickel (µg/L) 1.5 ± 0.03 1.5 ± 0.1 0.491 Urine cadmium/creatinine (µg/g) mean ± SD 4.5 ± 4.3 12 ± 22.8 < 0.001 median (IQR) 2.9 (1.9–5.9) 5.6 (2.5–13.5) < 0.001 Urine nickel (µg/L) mean ± SD 4.5 ± 7.7 6.3 ± 21.6 0.574 median (IQR) 2.2 (1.4–3.9) 2.2 (1.4–4.1) 0.574 PaO 2 /FiO 2 (mm Hg) 347 (270–412) 158 (118–215) < 0.001 Mechanical ventilator use 35 (71.4%) 181 (100%) < 0.001 Hospital mortality 9 (18.4%) 78 (43.1%) 0.002 Data are presented as mean ± standard deviation, count (%) or median (interquartile range). APACHE Acute Physiology and Chronic Health Evaluation, ARDS acute respiratory distress syndrome, CRP C-reactive protein, FiO 2 fraction of inspired oxygen, ICU intensive care unit, IL interleukin, IQR interquartile range, PaO 2 partial pressure of oxygen in arterial blood, SD standard deviation, SOFA Sequential Organ Failure Assessment, WBC white blood cells a Available for 47 ICU control patients and 155 ARDS patients No significantly difference in blood cadmium or nickel concentrations were observed between the two groups. Urinary cadmium/creatinine concentrations were significantly higher in the ARDS group than in the control group (median value: 5.6 [2.5–13.5] µg/g versus 2.9 [1.9–5.9] µg/g, p < 0.001). No significant differences in urine nickel concentration were observed between the two groups. Mechanical ventilator use was significantly higher in ARDS patients. All-cause hospital mortality was significant higher in the ARDS group than in the ICU control group (43.1% vs. 18.4%, p = 0.002). Comparisons of surviving and non-surviving ARDS patients As shown in Table 2 , no significant differences in age or gender distribution were observed between ARDS survivors and non-survivors. BMI was significantly higher among survivors. The etiologies of ARDS were comparable between the two groups. A significant difference in smoking history was observed between the two groups ( p = 0.039), including a higher percentage of current and former smokers among non-survivors, and higher percentage of never-smokers among survivors. The proportion of patients with immunocompromised status was significantly higher among non-survivors ( p < 0.001). APACHE II and SOFA scores were significantly higher among non-survivors than among survivors (both p < 0.05). Neutrophil-to-lymphocyte ratios were significantly higher among son-survivors than among survivors. Table 2 Baseline characteristics and clinical variables of ARDS patients: Survivors versus non-survivors Variables Survivors Non-survivors p value ( n = 103) ( n = 78) Age (years) 64.1 ± 14.8 64.5 ± 11.2 0.870 Male (gender) 76 (73.8%) 59 (75.6%) 0.777 Body mass index (kg/m 2 ) 25.3 ± 5 22.6 ± 3.7 < 0.001 ARDS etiologies Bacterial pneumonia 62 (60.2%) 55 (70.5%) 0.150 COVID-19 25 (24.3%) 15 (19.2%) 0.418 Aspiration pneumonia 5 (4.9%) 4 (5.1%) 1.000 Influenza pneumonia 5 (4.9%) 2 (2.6%) 0.700 Extrapulmonary sepsis 1 (1%) 2 (2.6%) 0.578 Others 5 (4.9%) 0 (0%) Smoking history 0.039 Current smoker 18 (17.5%) 23 (29.5%) Former smoker 21 (20.4%) 21 (26.9%) Never smoked 64 (62.1%) 34 (43.6%) Hypertension 52 (50.5%) 36 (46.2%) 0.564 Diabetes mellitus 35 (34%) 27 (34.6%) 0.929 Chronic heart disease 15 (14.6%) 9 (11.5%) 0.552 Chronic lung disease 25 (24.3%) 12 (15.4%) 0.142 Chronic liver disease 12 (11.7%) 6 (7.7%) 0.378 Chronic kidney disease 15 (14.6%) 14 (17.9%) 0.539 Immunocompromised status 36 (35%) 48 (61.5%) < 0.001 APACHE II score 14.8 ± 6.5 18.9 ± 7.3 < 0.001 SOFA score 7.3 ± 3.6 10.5 ± 3.3 < 0.001 WBC (10 3 /µL) 10.9 ± 5.5 11.2 ± 8.5 0.783 Neutrophil (%) 86.6 (78.9–90.6) 90 (83.3–93.4) 0.528 Lymphocyte (%) 7.3 (4–10.2) 4.3 (2–7.7) 0.188 Neutrophil/lymphocyte ratio 11.9 (7.5–22.9) 20.2 (10.5–47.1) 0.003 Hemoglobin (g/dL) 10.2 ± 2.3 9.4 ± 1.6 0.010 Platelets (10 3 /µL) 166 (121–254) 105 (51–208) < 0.001 Serum creatinine (mg/dL) 1.0 (0.5–1.9) 1 (0.5–2.5) 0.255 Bilirubin (total) (mg/dL) 0.5 (0.3–0.7) 0.5 (0.3–0.8) 0.798 Lactate (mg/dL) 12.1 (8.9–16.3) 14.5 (10.2–19.3) 0.215 CRP (mg/L) 135.4 (50.5–194) 112.8 (60.1–193.8) 0.795 IL-6 (pg/mL) a 31.1 (9.6–126) 54.6 (17.6–198) 0.600 PaO 2 /FiO 2 (mm Hg) 184 (131–273) 150 (113–196) 0.080 Blood cadmium (µg/L) 0.8 ± 0.4 0.8 ± 0.5 0.976 Blood nickel (µg/L) 1.5 ± 0.2 1.5 ± 0.1 0.471 Urine cadmium/creatinine (µg/g) mean ± SD 8.1 ± 8.7 17.2 ± 32.6 0.019 median (IQR) 4.5 (2.3–11.2) 7.2 (3.9–16.8) 0.019 Urine nickel (µg/L) mean ± SD 3.9 ± 7.2 4.5 ± 6.3 0.551 median (IQR) 2.1 (1.4–3.6) 2.2 (1.6–4.7) 0.551 Data are presented as mean ± standard deviation, count (%) or median (interquartile range). APACHE Acute Physiology and Chronic Health Evaluation, ARDS acute respiratory distress syndrome, COVID-19 coronavirus disease 2019, CRP C-reactive protein, FiO 2 fraction of inspired oxygen, IL interleukin, IQR interquartile range, PaO 2 partial pressure of oxygen in arterial blood, SD standard deviation, SOFA Sequential Organ Failure Assessment, WBC white blood cells a Available for 155 ARDS patients No significant differences in blood cadmium, blood nickel, or urine nickel concentrations were observed between groups. Urinary cadmium/creatinine concentrations were significantly higher among non-survivors than among survivors (median value) 7.2 [3.9–16.8] µg/g versus 4.5 [2.3–11.2] µg/g, p = 0.019). No significant difference in cadmium concentrations in BAL samples was observed between the two groups (Table 3 ). Table 3 Cadmium concentrations in bronchoalveolar lavage fluid from ARDS patients: Survivors versus non-survivors Variables Survivors Non-survivors p value ( n = 32) ( n = 25) BAL cadmium (µg/L) a 0.081 (0.04–0.161) 0.056 (0.031–0.137) 0.348 Data are presented as mean ± standard deviation, count (%) or median (interquartile range). ARDS acute respiratory distress syndrome, BAL bronchoalveolar lavage a Available for 57 ARDS patients Comparing ARDS patients with high and low urinary cadmium/creatinine levels ARDS patients were stratified into a high urinary cadmium/creatinine group (105 patients; 58%) and low urinary cadmium/creatinine group (76 patients; 42%) based on a maximum Youden index cutoff of 4.55 µg/g at ARDS onset (Table 4 ). Table 4 Clinical variables of ARDS patients stratified by urinary cadmium/creatinine ratio Variables Urinary cadmium/creatinine High ( n = 105) (> 4.55 µg/g) Low ( n = 76) (≤ 4.55 µg/g) p value Age (years) 66.4 ± 11.7 61.4 ± 14.9 0.016 Male (gender) 73 (69.5%) 62 (81.6%) 0.066 Body mass index (kg/m 2 ) 23.3 ± 4 25.2 ± 5.2 0.009 Smoking history 0.963 Current smoker 24 (22.9%) 17 (22.4%) Former smoker 25 (23.8%) 17 (22.4%) Never smoked 56 (53.3%) 42 (55.2%) APACHE II score at day 1 17 ± 7 15.9 ± 7.3 0.299 SOFA score at day 1 9 ± 3.7 8.3 ± 3.9 0.221 SOFA score at day 3 9.1 ± 4.1 7.7 ± 3.7 0.022 SOFA score at day 7 8.9 ± 4.2 7.6 ± 3.7 0.040 Laboratory data at day 1 WBC (10 3 /µl) 10.7 ± 7.4 11.5 ± 6.1 0.436 Neutrophil (%) 88.8 (81.4–93.1) 86.4 (76.5–91.1) 0.367 Lymphocyte (%) 5 (2.9–9.5) 6.4 (3.8–10) 0.682 Neutrophil/lymphocyte ratio 16.1 (8.4–32.7) 13.9 (7.9–24.4) 0.174 Hemoglobin (g/dL) 9.7 ± 2.1 10.1 ± 2 0.169 Platelets (10 3 /µL) 153.2 ± 112.5 185 ± 98.7 0.046 Serum creatinine (mg/dL) 0.8 (0.5–1.5) 1.1 (0.6–2.5) 0.131 Bilirubin (total) (mg/dL) 0.5 (0.3–0.8) 0.4 (0.3–0.7) 0.588 Lactate (mg/dl) 14.5 (11.6–20.5) 10.5 (7.6–14.5) 0.002 CRP (mg/l) 129.9 (60.1–197.7) 115.3 (47.3–180.3) 0.323 Procalcitonin (ng/ml) 2.1 (0.4–8.6) 1.8 (0.3–16.4) 0.836 IL-6 (pg/mL) a 39 (12.5–215.3) 28.3 (12.5–124.5) 0.034 Blood cadmium (µg/L) 0.9 ± 0.6 0.7 ± 0.3 0.002 Blood nickel (µg/L) 1.5 ± 0.1 1.5 ± 0.2 0.718 Urine cadmium/creatinine (µg/g) mean ± SD 20 ± 29.7 2.5 ± 1.3 < 0.001 median (IQR) 12.3 (6.7–21.2) 2.3 (1.4–3.7) < 0.001 Urine nickel (µg/L) mean ± SD 4.6 ± 7.9 3.5 ± 5 0.316 median (IQR) 2.2 (1.4–4.7) 1.9 (1.4–3.8) 0.316 PaO 2 /FiO 2 (mm Hg) 159.4 ± 62 185.3 ± 92 0.036 Data are presented as mean ± standard deviation, count or median (interquartile range) APACHE Acute Physiology and Chronic Health Evaluation, ARDS acute respiratory distress syndrome, CRP C-reactive protein, FiO 2 fraction of inspired oxygen, IL interleukin, IQR interquartile range, PaO 2 partial pressure of oxygen in arterial blood, SD standard deviation, SOFA Sequential Organ Failure Assessment, WBC white blood cells a Available for 155 ARDS patients The high-level group was older and had significantly lower BMI (both p < 0.05). SOFA scores were higher in the high urinary cadmium/creatinine group, reaching the level of significance at day 3 and day 7 after ARDS onset. No significant difference in smoking history was observed between the two groups. IL-6 levels were significantly higher in the high urinary cadmium/creatinine group ( p = 0.034). Blood and urinary cadmium concentrations were both significantly higher in the high urinary cadmium/creatinine group (both p < 0.05), whereas no significant difference was observed in blood or urinary nickel values. Patients in the high urinary cadmium/creatinine group faced a significantly higher risk of hypoxemia (i.e. lower PaO 2 /FiO 2 , p = 0.036). Clinical outcomes of ARDS patients by urinary cadmium/creatinine level As shown in Table 5 , 28-, 60-, 90-day, and all-cause hospital mortality rates were significantly higher in the high urinary cadmium/creatinine group (all p < 0.05). This group also had a higher incidence of shock and using inotropic agents. No significant differences were observed between two groups in terms of new-onset acute kidney injury, renal replacement therapy, duration of mechanical ventilator, length of ICU stay, or length of hospital stay. Table 5 Clinical outcomes of ARDS patients stratified by urinary cadmium/creatinine levels Outcomes Urinary cadmium/creatinine High ( n = 105) (> 4.55 µg/g) Low ( n = 76) (≤ 4.55 µg/g) p value Mortality 28-day hospital mortality 36 (34.3%) 11 (14.5%) 0.003 60-day hospital mortality 49 (46.7%) 20 (26.3%) 0.005 90-day hospital mortality 54 (51.4%) 23 (30.3%) 0.003 All cause hospital mortality 55 (52.4%) 23 (30.3%) 0.003 Shock status 84 (80%) 55 (72.3%) 0.230 Inotropic agents use 82 (78.1%) 48 (63.2%) 0.027 Acute kidney injury 40 (38.1%) 28 (36.8%) 0.864 Renal replacement therapy a 17 (16.2%) 16 (21.1%) 0.403 Duration of mechanical ventilator (days) 18 (10–31) 16 (9–32) 0.654 Length of ICU stay (days) 20 (13–34) 19 (12–33) 0.636 Length of hospital stay (days) 35 (21–62) 34 (20–51) 0.421 Data are presented as mean ± standard deviation, count (%) or median (interquartile range) ARDS acute respiratory distress syndrome, ICU intensive care unit a Excluded participants with end-stage renal disease requiring maintenance hemodialysis Factors associated with hospital mortality in ARDS patients After adjusting for significant confounding parameters, multivariable logistic regression models revealed a number of factors that were positively correlated with hospital mortality in ARDS patients: lower BMI, current smoking, immunocompromised status, higher SOFA score, and higher urinary cadmium/creatinine. ARDS patients with high urinary cadmium/creatinine values faced a significantly higher odds of hospital mortality (adjusted OR 1.031, [95% CI 1.001–1.062], p = 0.045). Among the studied variables, a urinary cadmium/creatinine value of > 4.55 µg/g had the greatest predictive value and was independently associated with hospital mortality (adjusted OR 2.365, [95% CI 1.003–5.578], p = 0.049) (Table 6 ). The 90-day survival rate was significantly higher in the low urinary cadmium/creatinine value group (≤ 4.55 µg/g) than in the high urinary cadmium/creatinine group (> 4.55 µg/g) (69.7% vs. 48.6%, p = 0.003, log-rank test) (Fig. 2 ). Table 6 Multivariable logistic regression analysis of factors associated with hospital mortality in ARDS patients Variables Univariable analysis Multivariable analysis model 1 Multivariable analysis model 2 OR (95% CI) p value Adjusted OR (95% CI) p value Adjusted OR (95% CI) p value Age (with each year increase) 1.002 (0.980–1.024) 0.874 Body mass index 0.867 (0.804–0.935) < 0.001 0.869 (0.787–0.959) 0.005 0.868 (0.783–0.963) 0.008 Bacterial pneumonia 1.581 (0.845–2.959) 0.152 Smoking (current) 1.975 (0.977–3.992) 0.058 2.827(1.026–7.786) 0.044 Smoking (former) 1.199 (0.848–1.696) 0.304 Smoking (never) 0.778 (0.637–0.950) 0.014 Chronic lung disease 0.567 (0.265–1.216) 0.145 Immunocompromised status 2.978 (1.618–5.480) < 0.001 2.369 (1.063–5.276) 0.035 SOFA score 1.298 (1.176–1.434) < 0.001 1.323 (1.172–1.492) < 0.001 1.203 (1.054–1.374) 0.006 Neutrophil/lymphocyte ratio 1.016 (1.005–1.027) 0.004 Hemoglobin 0.825 (0.706–0.965) 0.016 Platelets 0.994 (0.991–0.998) 0.001 Serum creatinine 1.071 (0.950–1.208) 0.263 Lactate 1.020 (0.988–1.053) 0.219 PaO 2 /FiO 2 0.997 (0.993–1.001) 0.098 Blood nickel 0.392 (0.026–5.841) 0.497 Blood cadmium 1.009 (0.560–1.816) 0.976 Urine nickel 1.013 (0.970–1.058) 0.553 Urine cadmium/creatinine 1.037 (1.010–1.065) 0.007 1.031 (1.001–1.062) 0.045 Urine cadmium/creatinine > 4.55 µg/g 2.587 (1.388–4.821) 0.003 2.365 (1.003–5.578) 0.049 ARDS acute respiratory distress syndrome, CI confidence interval, FiO 2 fraction of inspired oxygen, OR odds ratio, PaO 2 partial pressure of oxygen in arterial blood, SOFA Sequential Organ Failure Assessment For the continuous variables, the odds ratio indicates that the odds of hospital mortality increases or decreases per unit increase of these variables Model 1: add urine cadmium/creatinine as a continuous variable Model 2: add urine cadmium/creatinine > 4.55 µg/g as a categorical variable Discussion The principle finding of this study is that urinary cadmium levels at ARDS onset were independently and positively associated with hospital mortality, and could be a valuable early prognostic indicator. Cadmium and nickel are considered environmental immunotoxicants. Cadmium is a cumulative toxin, whereas nickel is not. Chronic cadmium exposure almost invariably produces toxic or carcinogenic effects, with the kidney being the primary target organ. Cadmium elimination is slow, with retention predominantly in renal tubular cells. Its biological half-life is 75–128 days in blood and 6–38 years in renal tissue. Thus, urinary cadmium concentrations are generally treated as an indicator of chronic exposure and total body load, whereas blood concentrations serve as an indicator of acute or recent exposure [ 10 – 13 ]. Exposure to cadmium or nickel can alter gene regulation, disrupt redox balance, elicit ROS accumulation, trigger oxidative stress, impair antioxidant defense systems, induce endoplasmic reticulum stress, instigate mitochondrial apoptosis, autophagy and thereby amplify inflammation and immunotoxicity—of which can have a detrimental effect on body tissues and organ systems [ 8 – 13 , 22 – 24 ]. Chronic cadmium exposure can aggravate oxidative stress, airway inflammation, and lung injury, making it a risk factor for more severe disease in conditions such as lower respiratory tract infections [ 14 , 25 , 26 ]. Oxidative stress and cytokine storm play central roles in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, driving dysregulated inflammation, immune activation, endothelial injury, immunothrombosis, tissue damage, and multiorgan dysfunction [ 27 – 29 ]. A number of recent studies have reported correlations between urinary cadmium levels and the severity and clinical outcomes of COVID-19 [ 14 – 17 ]. In our recent report, patients with severe COVID-19 who were in the highest quartile of urinary cadmium-to-creatinine ratio exhibited a significantly higher risk of all-cause hospital mortality [ 15 ]. Oxidative stress is also central to the pathophysiology of ARDS, causing injury to alveolar epithelial and capillary endothelial cells as well as increased alveolar capillary barrier permeability, impaired gas exchange, and dysregulation of both local (i.e., alveolar) and systemic inflammation and immune activation [ 18 – 20 ]. Cadmium and nickel exposure may exacerbate these processes, but prior to this study, their roles in ARDS pathophysiology and outcomes had not been examined. In our cohort, we observed higher urinary cadmium values in ARDS patients than in ICU control patients. We also observed significantly higher values for inflammatory markers, including the neutrophil to lymphocyte ratio, CRP, and IL-6. Compared with ICU control patients, ARDS patients presented a significantly elevated risk of organ failure (i.e., higher APACHE II and SOFA scores) and hospital mortality (43.1% vs. 18.4%, p = 0.002). Compared with survivors of ARDS, non-survivors exhibited significantly elevated concentrations of urinary cadmium, neutrophil to lymphocyte ratios, and APACHE II and SOFA scores. Multivariable regression analysis confirmed that urinary cadmium/creatinine was independently associated with hospital mortality in ARDS patients (adjusted OR 1.031, p = 0.045). Our above findings suggest that high urinary cadmium concentrations, indicative of cadmium bioaccumulation, can exacerbate the effects of oxidative stress and dysregulated inflammatory responses during the course of ARDS, contributing to apoptosis, tissue injury, and organ dysfunction. Moreover, high urinary cadmium levels can increase the susceptibility of critically ill patients to developing ARDS, following predisposing factors such as sepsis and pneumonia, and an elevated risk of mortality among ARDS patients. Urinary cadmium could therefore be regarded as a prognostic biomarker. Among ARDS patients, those in the high urinary cadmium/creatinine group had significantly higher IL-6 values and a higher risk of hypoxemia (i.e. lower PaO 2 /FiO 2 ). The high urinary cadmium/creatinine group had significantly higher 28-, 60-, 90-day, and all-cause hospital mortality. Note that urinary cadmium concentration is a surrogate marker of chronic cadmium exposure and lifetime accumulation, indicating that these ARDS patients were prone to the effects of cadmium, including oxidative stress, persistent inflammation, impaired gas exchange, and even an increased risk of mortality. In contrast, blood cadmium and nickel, and urinary nickel concentrations—reflecting recent exposure—did not differ significantly between ARDS and control patients or between survivors and non-survivors. Moreover, we analyzed cadmium concentrations in the BAL fluid (i.e., the local alveolar environment) of 57 ARDS patients and found no significant difference between survivors and non-survivors. This suggests that long-term cadmium accumulation is of greater relevance than short-term cadmium exposure or cadmium levels in the local environment in predicting the risk and prognosis of ARDS. Smoking is a major cadmium source and is known to impair antioxidant systems, increase ROS burden, induce oxidative stress, and predispose the lungs to acute injury following triggers such as sepsis [ 4 , 10 – 13 , 30 ]. One prospective multicenter cohort study developed a lung injury prediction score that identified smoke inhalation as the predisposing condition most strongly correlated to acute lung injury [ 31 ]. Another prospective study reported that smoking is a risk factor for ARDS [ 32 ]. One systematic review and meta-analysis concluded that smoking increased the risk of ARDS [ 33 ]. In the current study, the proportion of patients with a current and former history of smoking were higher in the ARDS group than in the ICU control group, although the difference did not reach the level of significance. Moreover, smoking history differed significantly between survivors and non-survivors of ARDS ( p = 0.039), and current smoking history was independently associated with hospital mortality (adjusted OR 2.827, p = 0.044). Thus, it is reasonable to speculate that chronic cigarette smoking may be the primary source of chronic cadmium exposure in our ARDS patients, potentially amplifying oxidative stress and accelerating inflammation during the course of ARDS, thereby contributing to increased hospital mortality. This study was subject to several limitations, which should be considered in the interpretation of our findings. First, this cohort study was conducted at a single tertiary care referral center in Taiwan, such that the results are not necessarily generalizable to other institutions. Second, while urinary cadmium levels were corrected for creatinine to account for urine dilution, urinary nickel values were not routinely creatinine-corrected in our institution. Third, our analysis did not investigate the extent of oxidative stress biomarkers, such as the imbalance between ROS production and antioxidant enzymes, including superoxide dismutase and glutathione peroxidase. Fourth, as a prospective observational study, causality cannot be established. Finally, this study did not explore the molecular mechanisms of heavy metal–induced lung injury, and the precise pathophysiology of ARDS warrants further mechanistic and experimental studies. Conclusions Exposure to environmental cadmium may increase susceptibility to ARDS in critically ill patients, and has prognostic value in established ARDS cases. In our cohort, urinary cadmium concentrations at ARDS onset were independently associated with hospital mortality. These findings underscore the need for public health policies to reduce chronic cadmium exposure, which may lower ARDS incidence and improve outcomes. Elucidating the molecular mechanisms of heavy metal–mediated lung injury will be crucial for developing prognostic biomarkers and targeted therapies for ARDS. Abbreviations APACHE Acute Physiology and Chronic Health Evaluation ARDS acute respiratory distress syndrome BAL bronchoalveolar lavage BMI body mass index CI confidence interval COVID-19 coronavirus disease 2019 CRP C-reactive protein ICU intensive care unit IL interleukin OR odds ratio ROS reactive oxygen species SOFA sequential organ failure assessment. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki after receiving approval from the Institutional Review Board for Human Research of Chang Gung Memorial Hospital (CGMH IRB No. 202100595A3, 202201833A3, and 202300897A3), and informed consent from all study participants. Consent for publication Not applicable. Availability of data and materials The datasets used or analyzed in the study are available from the corresponding author upon reasonable request. Competing interests On behalf of all authors, the corresponding author states that there are no conflicts of interest. Funding This study was supported by grants from Chang Gung Memorial Hospital (CMRPG3L0821, CMRPG3L0822, CORPG3M0331, and CMRPG3N1121), the Taiwan Ministry of Science and Technology (MOST 111-2314-B-182A-148), and the Taiwan National Science and Technology Council (NSTC114-2314-B-182-065-). Authors’ contributions LCC and THY assume responsibility for the accuracy of the data analysis and drafting of the manuscript. LCC, HHL, HWK, PCH, CSL, and THY performed the study design and data acquisition. LCC, TMC, and SCHK were responsible for statistical analysis of data. LCC, HHL, HWK and THY interpretation the results. All authors contributed to the completion of the manuscript and have approved the final version. Acknowledgements The authors would like to express their appreciation for the patients and staff in the general wards and ICU at Chang Gung Memorial Hospital, Linkou branch, Taiwan. References Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):18. Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet. 2022;400(10358):1145–1156. Qadir N, Sahetya S, Munshi L, Summers C, Abrams D, Beitler J, et al. An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2024;209(1):24–36. Bennett RM, Reilly JP. Environmental Risk Factors for Acute Respiratory Distress Syndrome. Clin Chest Med. 2024;45(4):797–807. Shetty SS, D D, S H, Sonkusare S, Naik PB, Kumari N S, et al. Environmental pollutants and their effects on human health. Heliyon. 2023;9(9):e19496. Gutman L, Pauly V, Orleans V, Piga D, Channac Y, Armengaud A, et al. Long-term exposure to ambient air pollution is associated with an increased incidence and mortality of acute respiratory distress syndrome in a large French region. Environ Res. 2022;212(Pt D):113383. Reilly JP, Zhao Z, Shashaty MGS, Koyama T, Jones TK, Anderson BJ, et al. Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis. Intensive Care Med. 2023;49(8):957–965. Koyama H, Kamogashira T, Yamasoba T. Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies. Antioxidants (Basel). 2024;13(1):76. Jomova K, Alomar SY, Nepovimova E, Kuca K, Valko M. Heavy metals: toxicity and human health effects. Arch Toxicol. 2025;99(1):153–209. Hossein-Khannazer N, Azizi G, Eslami S, Alhassan Mohammed H, Fayyaz F, Hosseinzadeh R, et al. The effects of cadmium exposure in the induction of inflammation. Immunopharmacol Immunotoxicol. 2020;42(1):1–8. Charkiewicz AE, Omeljaniuk WJ, Nowak K, Garley M, Nikliński J. Cadmium Toxicity and Health Effects-A Brief Summary. Molecules. 2023;28(18):6620. Yang Y, Hassan MF, Ali W, Zou H, Liu Z, Ma Y. Effects of Cadmium Pollution on Human Health: A Narrative Review. Atmosphere. 2025; 16(2):225. Rasin P, Ashwathi AV, Basheer SM, Haribabu J, Santibanez JF, Garrote CA, Arulraj A and Mangalaraja RV. Exposure to cadmium and its impacts on human health: a short review. Journal of Hazardous Materials Advances. 2025;17;100608. Skalny AV, Lima TRR, Ke T, Zhou JC, Bornhorst J, Alekseenko SI, et al. Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases. Food Chem Toxicol. 2020;146:111809. Chiu LC, Lee CS, Hsu PC, Li HH, Chan TM, Hsiao CC, et al. Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study. Environ Health. 2024;23(1):29. Baumert BO, Wang H, Samy S, Park SK, Lam CN, Dunn K, et al. Environmental pollutant risk factors for worse COVID-19 related clinical outcomes in predominately hispanic and latino populations. Environ Res. 2024;252(Pt 4):119072. Zeng HL, Zhang B, Wang X, Yang Q, Cheng L. Urinary trace elements in association with disease severity and outcome in patients with COVID-19. Environ Res. 2021;194:110670. Bezerra FS, Lanzetti M, Nesi RT, Nagato AC, Silva CPE, Kennedy-Feitosa E, Melo AC, Cattani-Cavalieri I, Porto LC, Valenca SS. Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries. Antioxidants (Basel). 2023;12(3):548. Lim EY, Lee SY, Shin HS, Kim GD. Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome. Antioxidants (Basel). 2023;12(11):2016. Wang F, Ge R, Cai Y, Zhao M, Fang Z, Li J, Xie C, Wang M, Li W, Wang X. Oxidative stress in ARDS: mechanisms and therapeutic potential. Front Pharmacol. 2025;16:1603287. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–2533. Guo H, Liu H, Jian Z, Cui H, Fang J, Zuo Z, et al. Immunotoxicity of nickel: Pathological and toxicological effects. Ecotoxicol Environ Saf. 2020;203:111006. Genchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020;17(3):679. Yin H, Wang C, Guo H, Li X, Liu J. The mechanism of nickel-induced autophagy and its role in nephrotoxicity. Ecotoxicol Environ Saf. 2024;273:116150. Park SK, Sack C, Sirén MJ, Hu H. Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults. Environ Health Perspect. 2020;128(12):127004. Larson-Casey JL, Liu S, Pyles JM, Lapi SE, Saleem K, Antony VB, Gonzalez ML, Crossman DK, Carter AB. Impaired PPARγ activation by cadmium exacerbates infection-induced lung injury. JCI Insight. 2023;8(9):e166608. Alam MS, Czajkowsky DM. SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities. Cytokine Growth Factor Rev. 2022;63:44–57. Wieczfinska J, Kleniewska P, Pawliczak R. Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections. Oxid Med Cell Longev. 2022;2022:5589089. Gain C, Song S, Angtuaco T, Satta S, Kelesidis T. The role of oxidative stress in the pathogenesis of infections with coronaviruses. Front Microbiol. 2023;13:1111930. Seo YS, Park JM, Kim JH, Lee MY. Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants (Basel). 2023;12(9):1732. Gajic O, Dabbagh O, Park PK, Adesanya A, Chang SY, Hou P, et al; U.S. Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med. 2011;183(4):462–70. Moazed F, Hendrickson C, Jauregui A, Gotts J, Conroy A, Delucchi K, et al. Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers. Am J Respir Crit Care Med. 2022;205(8):927–935. Zhang L, Xu J, Li Y, Meng F, Wang W. Smoking on the risk of acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care. 2024;28(1):122. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9086457","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":629699917,"identity":"c005c3c8-d175-4f77-b60f-b9d09c3c5c34","order_by":0,"name":"Li-Chung Chiu","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li-Chung","middleName":"","lastName":"Chiu","suffix":""},{"id":629699918,"identity":"823cafa3-0d1d-46b7-906a-3d95e8f06a2f","order_by":1,"name":"Hsin-Hsien Li","email":"","orcid":"","institution":"Chang Gung University","correspondingAuthor":false,"prefix":"","firstName":"Hsin-Hsien","middleName":"","lastName":"Li","suffix":""},{"id":629699919,"identity":"0f452d5a-7fdf-486c-9d22-b75ac25248c7","order_by":2,"name":"How-Wen Ko","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"How-Wen","middleName":"","lastName":"Ko","suffix":""},{"id":629699920,"identity":"f5a701ed-e7c3-48e7-a2ad-6d703eca5410","order_by":3,"name":"Ping-Chih Hsu","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ping-Chih","middleName":"","lastName":"Hsu","suffix":""},{"id":629699921,"identity":"a148fca4-8a58-46b6-b71a-0f0bf30f0677","order_by":4,"name":"Chung-Shu Lee","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chung-Shu","middleName":"","lastName":"Lee","suffix":""},{"id":629699922,"identity":"37dd9a3b-de5b-46f2-9da7-6cbc9978cd25","order_by":5,"name":"Tien-Ming Chan","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tien-Ming","middleName":"","lastName":"Chan","suffix":""},{"id":629699923,"identity":"59022aac-8026-4daa-a82e-6d11d270f796","order_by":6,"name":"Scott Chih-Hsi Kuo","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Scott","middleName":"Chih-Hsi","lastName":"Kuo","suffix":""},{"id":629699924,"identity":"5309dd3a-3a11-4316-b5b0-2e6862b232ab","order_by":7,"name":"Tzung-Hai Yen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYDACZubjn/8Y2ABZPMRqYWdLY+CpSENoIayTn8eMgefMYRK06DbzmD2QbDsvLx929gDDxz21DPYSCfi1mB1mKzcwbLttuPF2XgLjjGfHGXgIa2HeIJHYdjvBcHaOATPPgWMMPNIEtTAYSBxsO0eSFhYzyYYzBxLkpcFaaojRwpZszFCRbLgBqOXgjAMHeHjuPyCg5fzhg48ZDOzk5WfnGD74cKBOjr3nAH4tcGAAVAhEh4lOAwwM8g1gqo54HaNgFIyCUTBiAACqNUKk41sJWwAAAABJRU5ErkJggg==","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Tzung-Hai","middleName":"","lastName":"Yen","suffix":""}],"badges":[],"createdAt":"2026-03-10 16:53:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9086457/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9086457/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108384279,"identity":"b9d8c3ae-ee22-4b62-85ca-2c5e4fe836fa","added_by":"auto","created_at":"2026-05-04 05:52:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":507421,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the process of enrolling critically ill patients with and without acute respiratory distress syndrome (ARDS).\u003c/p\u003e\n\u003cp\u003eARDS, acute respiratory distress syndrome; ESRD, end-stage renal disease; ICU, intensive care unit; U-CdCr, urinary cadmium-to-creatinine ratio.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9086457/v1/20b1bfd4f26bc9e303c7430a.png"},{"id":108492410,"identity":"e2e032e6-cb1e-4b66-862f-635d2c31e9ac","added_by":"auto","created_at":"2026-05-05 09:57:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":512798,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier 90-day survival curves for ARDS patients stratified by urinary cadmium-to-creatinine ratio (U-CdCr), using an optimal cutoff value of 4.55 μg/g at disease onset.\u003c/p\u003e\n\u003cp\u003eARDS, acute respiratory distress syndrome; U-CdCr, urinary cadmium-to-creatinine ratio.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9086457/v1/f46ac7989afe62f4cfe540c0.png"},{"id":108495100,"identity":"17c1410b-3ca4-4a79-ba4c-2bc754313c3f","added_by":"auto","created_at":"2026-05-05 10:08:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1659445,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9086457/v1/3aa6c358-4aea-477a-95d9-4e4da4c23236.pdf"},{"id":108384281,"identity":"9bc1b727-6407-4bef-ab69-96ce194768de","added_by":"auto","created_at":"2026-05-04 05:52:24","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":23752,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-9086457/v1/fa8994bcdf30309a9d475c13.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between urinary cadmium concentrations and hospital mortality in acute respiratory distress syndrome: a prospective observational cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eAcute respiratory distress syndrome (ARDS) is a potentially lethal form of acute respiratory failure characterized by profound hypoxemia resulting from pulmonary or extrapulmonary clinical insult. The condition contributes to multiple organ failure and increases the risk of mortality. Current ARDS management strategies focus mainly on lung-protective ventilation strategies and lack specific pharmacological therapies [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Reducing morbidity and mortality among critically ill patients requires a clear understanding of all risk factors that predispose patients to ARDS onset and progression.\u003c/p\u003e \u003cp\u003eHeavy metal pollutants pose a considerable threat to public health, due to their adverse effects on inflammation, oxidative stress, mitochondrial dysfunction, and overall organ health. Numerous environmental pollutants have been linked to disruption of the alveolar capillary barrier, recruitment of inflammatory cells, excessive cytokine release, and endothelial injury\u0026mdash;factors that increase lung vulnerability to ARDS in patients such as pneumonia or sepsis [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe main routes of heavy metal exposure are airborne pollutants, occupational exposure, contaminated drinking water and diet, tobacco, and dermal contact. Heavy metal toxicity depends on the inherent properties of the metal, the degree of bioaccumulation, and the exposure dose, route, and frequency. Heavy metal exposure has been shown to disrupt cellular redox homeostasis by reducing antioxidant levels, provoking excessive reactive oxygen species (ROS) production and oxidative stress, impairing the mitochondrial electron transport chain, and inducing stress in the endoplasmic reticulum, collectively contributing to apoptosis, endothelial cell injury, tissue damage, airway inflammation, ultimately leading to organ dysfunction [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCadmium and nickel are both recognized as heavy metal toxicants and carcinogens. Cadmium is a cumulative toxin with a relatively long half-life of 6 to 38 years, whereas nickel is a non-cumulative toxin with a half-life of 17 to 53 hours. Cadmium and nickel are predominantly excreted through urine. Urinary cadmium levels are considered surrogates of chronic exposure and total body burden, whereas urinary nickel concentrations are more indicative of recent acute exposure [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Exposure to cadmium or nickel has been identified as a risk factor for increased susceptibility to various infectious respiratory diseases, including coronavirus disease 2019 (COVID-19). Previous studies have reported possible links between cadmium or nickel exposure and COVID-19 severity and clinical outcomes [\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eARDS pathophysiology is characterized by oxidative stress, dysregulated airway and systemic inflammatory cascades, and immune cell activation [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, the potential impact of cadmium and nickel exposure on the development, severity, and clinical outcomes of ARDS remains unclear. This study investigated the potential association between cadmium and nickel exposures and clinical outcomes in patients with ARDS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients\u003c/h2\u003e \u003cp\u003e This prospective study enrolled patients who had been admitted to the intensive care unit (ICU) of a Taiwanese tertiary care referral center (Chang Gung Memorial Hospital, Linkou branch) between November 2021 and April 2025. Blood and urinary cadmium and nickel concentrations were collected within 3 days of the ARDS onset (ARDS patients) or ICU admission (control subjects). Bronchoalveolar lavage (BAL) was performed within one week of ARDS onset for pathogen identification in selected cases identified by the attending intensivist.\u003c/p\u003e \u003cp\u003eARDS was defined in accordance with the Berlin criteria [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The exclusion criteria included (1) age\u0026thinsp;\u0026lt;\u0026thinsp;20 years, (2) end-stage renal disease requiring maintenance dialysis, (3) acute kidney injury with oliguria, (4) mortality within 7 days after ARDS onset or after ICU admission (5) a history of residing in a cadmium or nickel contaminated area or working in a cadmium or nickel emitting industry (6) inability to obtain informed consent from patients or their legal representative.\u003c/p\u003e \u003cp\u003e This study was conducted in accordance with the Declaration of Helsinki, and approval was obtained from the Institutional Review Board of CGMH for Human Research (CGMH IRB No. 202100595A3, 202201833A3, and 202300897A3).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eDemographic data, smoking status, underlying comorbidities, and the etiology of ARDS were recorded for all participants. Blood and urinary cadmium and nickel concentrations as well as interleukin-6 (IL-6) levels were measured within 3 days of enrollment. Other clinical and laboratory variables including Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score were collected at days 1, 3, and 7 after ARDS onset (ARDS patients) or at days 1, 3, and 7 after ICU admission (control subjects).\u003c/p\u003e \u003cp\u003eAdditional recorded variable included dates of hospital and ICU admission, the presence of shock, the use of inotropic agents, renal replacement therapy, ARDS onset, mechanical ventilator initiation and liberation, ICU and hospital discharge, and time of death.\u003c/p\u003e\n\u003ch3\u003eOutcome measurements\u003c/h3\u003e\n\u003cp\u003ePrimary outcomes were 28-day, 60-day, 90-day, and all-cause hospital mortality. Secondary outcomes included use of inotropic agents, incidence of shock, occurrence of acute kidney injury (with or without renal replacement therapy), duration of mechanical ventilation, length of ICU stay, and length of hospital stay. Hospital mortality was defined as death from any cause during the hospital stay. Survivors were defined as patients alive 90 days after hospital discharge.\u003c/p\u003e\n\u003ch3\u003eMeasuring cadmium and nickel levels in blood and urine, and cadmium concentrations in bronchoalveolar lavage\u003c/h3\u003e\n\u003cp\u003eBlood specimens were collected in 6 mL plastic blood collection tubes containing K2EDTA as an anticoagulant (BD, Franklin Lakes, NJ, USA). Urine and BAL specimens were collected in 10 mL metal-free plastic collection tubes. All blood, urine and BAL specimens were stored at 4\u0026deg;C, prior to cadmium and nickel measurements conducted using inductively coupled plasma mass spectrometry. The relevant details pertaining to the methods used for the cadmium and nickel measurements are provided in Supplementary File 1.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as mean \u0026plusmn; standard deviation for normally distributed data, or as median and interquartile range for non-normally distributed data. A student\u0026rsquo;s t-test or the Mann\u0026ndash;Whitney U test was used to compare continuous variables between groups. Categorical variables were presented as counts and percentages, and comparisons were made using the chi-square test for equal proportions or Fisher\u0026rsquo;s exact test, as appropriate. Receiver operating characteristic curves were used to evaluate the value of variables in predicting the hospital mortality of ARDS patients. The Youden index was used to determine cutoff values to dichotomize continuous variables, categorizing ARDS patients into high or low urinary cadmium groups. Univariable analysis was first performed to identify risk factors associated with hospital mortality in ARDS patients, followed by the construction of multivariable logistic regression models using stepwise selection to adjust for potential confounding factors. The results were reported using odds ratio (OR) and 95% confidence interval (CI). Cumulative probabilities of hospital survival for each group were generated as a function of time using the Kaplan\u0026ndash;Meier method and compared using the log-rank test. All statistical analyses were conducted using SPSS version 29.0 (IBM Inc., Armonk, NY), and a two-sided \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom a total of 4517 patients admitted to ICU during the study period, 181 patients with ARDS and 49 patients without ARDS were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The overall all-cause hospital mortality among ARDS patients was 43.1%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eComparison of ARDS patients and ICU control patients without ARDS\u003c/h3\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, no significant difference in age or gender distribution was detected between the ARDS and ICU control groups. Mean body mass index (BMI) was significantly higher in the ARDS group than in the ICU control group. More than half of the patients enrolled in the study were never-smokers, and no significant difference in smoking history (current or former) was observed between the two groups. Comorbidity profiles were similar, except for a higher prevalence of chronic lung disease in the control group. APACHE II and SOFA scores were significantly higher in the ARDS group than in the ICU control group (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The detected values of inflammatory markers, such as neutrophil to lymphocyte ratio, C-reactive protein (CRP), and IL-6 were significantly higher in the ARDS group (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics and clinical variables of ICU controls versus ARDS patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICU controls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARDS patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.6 \u0026plusmn; 14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.3 \u0026plusmn; 13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (gender)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (61.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135 (74.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.7 \u0026plusmn; 4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.1 \u0026plusmn; 4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.819\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (59.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (54.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (34.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.852\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic lung disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (38.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic liver disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (9.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (6.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunocompromised status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (46.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.5 \u0026plusmn; 5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.6 \u0026plusmn; 7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7 \u0026plusmn; 3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.7 \u0026plusmn; 3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 \u0026plusmn; 5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1 \u0026plusmn; 6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.390\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.8 (77.5\u0026ndash;90.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.5 (80.4\u0026ndash;92.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7 (4.5\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8 (2.9\u0026ndash;9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil/lymphocyte ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7 (5.7\u0026ndash;17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.2 (8.2\u0026ndash;30.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.7 \u0026plusmn; 2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.9 \u0026plusmn; 2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e225.6 \u0026plusmn; 115.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166.6 \u0026plusmn; 107.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7 (0.5\u0026ndash;1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.5\u0026ndash;2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (total) (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6 (0.3\u0026ndash;0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5 (7\u0026ndash;14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.6 (9.6\u0026ndash;19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (22.3\u0026ndash;124.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127 (54.8\u0026ndash;193.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6 (pg/mL) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (4.8\u0026ndash;47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.4 (12.2\u0026ndash;163)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood cadmium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7 \u0026plusmn; 0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8 \u0026plusmn; 0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine cadmium/creatinine (\u0026micro;g/g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 \u0026plusmn; 4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 \u0026plusmn; 22.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1.9\u0026ndash;5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6 (2.5\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 \u0026plusmn; 7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.3 \u0026plusmn; 21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.2 (1.4\u0026ndash;3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2 (1.4\u0026ndash;4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e347 (270\u0026ndash;412)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158 (118\u0026ndash;215)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilator use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e181 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (43.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, count (%) or median (interquartile range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eAPACHE\u003c/em\u003e Acute Physiology and Chronic Health Evaluation, \u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eCRP\u003c/em\u003e C-reactive protein, \u003cem\u003eFiO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e fraction of inspired oxygen, \u003cem\u003eICU\u003c/em\u003e intensive care unit, \u003cem\u003eIL\u003c/em\u003e interleukin, \u003cem\u003eIQR\u003c/em\u003e interquartile range, \u003cem\u003ePaO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e partial pressure of oxygen in arterial blood, \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eSOFA\u003c/em\u003e Sequential Organ Failure Assessment, \u003cem\u003eWBC\u003c/em\u003e white blood cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eAvailable for 47 ICU control patients and 155 ARDS patients\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo significantly difference in blood cadmium or nickel concentrations were observed between the two groups. Urinary cadmium/creatinine concentrations were significantly higher in the ARDS group than in the control group (median value: 5.6 [2.5\u0026ndash;13.5] \u0026micro;g/g versus 2.9 [1.9\u0026ndash;5.9] \u0026micro;g/g, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences in urine nickel concentration were observed between the two groups. Mechanical ventilator use was significantly higher in ARDS patients. All-cause hospital mortality was significant higher in the ARDS group than in the ICU control group (43.1% vs. 18.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\n\u003ch3\u003eComparisons of surviving and non-surviving ARDS patients\u003c/h3\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, no significant differences in age or gender distribution were observed between ARDS survivors and non-survivors. BMI was significantly higher among survivors. The etiologies of ARDS were comparable between the two groups. A significant difference in smoking history was observed between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039), including a higher percentage of current and former smokers among non-survivors, and higher percentage of never-smokers among survivors. The proportion of patients with immunocompromised status was significantly higher among non-survivors (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). APACHE II and SOFA scores were significantly higher among non-survivors than among survivors (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Neutrophil-to-lymphocyte ratios were significantly higher among son-survivors than among survivors.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics and clinical variables of ARDS patients: Survivors versus non-survivors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurvivors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-survivors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.1 \u0026plusmn; 14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.5 \u0026plusmn; 11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (gender)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (73.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (75.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.3 \u0026plusmn; 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.6 \u0026plusmn; 3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARDS etiologies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (60.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (70.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (24.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (19.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspiration pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfluenza pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.700\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary sepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.578\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (29.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (26.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (43.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (50.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.552\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic lung disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (24.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic liver disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (11.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.378\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.539\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunocompromised status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (61.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8 \u0026plusmn; 6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.9 \u0026plusmn; 7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3 \u0026plusmn; 3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5 \u0026plusmn; 3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.9 \u0026plusmn; 5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.2 \u0026plusmn; 8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.783\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.6 (78.9\u0026ndash;90.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (83.3\u0026ndash;93.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3 (4\u0026ndash;10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3 (2\u0026ndash;7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil/lymphocyte ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.9 (7.5\u0026ndash;22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.2 (10.5\u0026ndash;47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.2 \u0026plusmn; 2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.4 \u0026plusmn; 1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166 (121\u0026ndash;254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (51\u0026ndash;208)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0 (0.5\u0026ndash;1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.5\u0026ndash;2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (total) (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5 (0.3\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.798\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1 (8.9\u0026ndash;16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5 (10.2\u0026ndash;19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135.4 (50.5\u0026ndash;194)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112.8 (60.1\u0026ndash;193.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.795\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6 (pg/mL) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.1 (9.6\u0026ndash;126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.6 (17.6\u0026ndash;198)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.600\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184 (131\u0026ndash;273)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e150 (113\u0026ndash;196)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood cadmium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8 \u0026plusmn; 0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8 \u0026plusmn; 0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine cadmium/creatinine (\u0026micro;g/g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.1 \u0026plusmn; 8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.2 \u0026plusmn; 32.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 (2.3\u0026ndash;11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2 (3.9\u0026ndash;16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9 \u0026plusmn; 7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5 \u0026plusmn; 6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1 (1.4\u0026ndash;3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2 (1.6\u0026ndash;4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, count (%) or median (interquartile range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eAPACHE\u003c/em\u003e Acute Physiology and Chronic Health Evaluation, \u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eCOVID-19\u003c/em\u003e coronavirus disease 2019, \u003cem\u003eCRP\u003c/em\u003e C-reactive protein, \u003cem\u003eFiO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e fraction of inspired oxygen, \u003cem\u003eIL\u003c/em\u003e interleukin, \u003cem\u003eIQR\u003c/em\u003e interquartile range, \u003cem\u003ePaO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e partial pressure of oxygen in arterial blood, \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eSOFA\u003c/em\u003e Sequential Organ Failure Assessment, \u003cem\u003eWBC\u003c/em\u003e white blood cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eAvailable for 155 ARDS patients\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo significant differences in blood cadmium, blood nickel, or urine nickel concentrations were observed between groups. Urinary cadmium/creatinine concentrations were significantly higher among non-survivors than among survivors (median value) 7.2 [3.9\u0026ndash;16.8] \u0026micro;g/g versus 4.5 [2.3\u0026ndash;11.2] \u0026micro;g/g, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019). No significant difference in cadmium concentrations in BAL samples was observed between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCadmium concentrations in bronchoalveolar lavage fluid from ARDS patients: Survivors versus non-survivors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurvivors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-survivors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;32)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;25)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBAL cadmium (\u0026micro;g/L) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.081 (0.04\u0026ndash;0.161)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.056 (0.031\u0026ndash;0.137)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.348\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, count (%) or median (interquartile range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eBAL\u003c/em\u003e bronchoalveolar lavage\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eAvailable for 57 ARDS patients\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparing ARDS patients with high and low urinary cadmium/creatinine levels\u003c/h2\u003e \u003cp\u003eARDS patients were stratified into a high urinary cadmium/creatinine group (105 patients; 58%) and low urinary cadmium/creatinine group (76 patients; 42%) based on a maximum Youden index cutoff of 4.55 \u0026micro;g/g at ARDS onset (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical variables of ARDS patients stratified by urinary cadmium/creatinine ratio\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUrinary cadmium/creatinine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;105)\u003c/p\u003e \u003cp\u003e(\u0026gt;\u0026thinsp;4.55 \u0026micro;g/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e \u003cp\u003e(\u0026le;\u0026thinsp;4.55 \u0026micro;g/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.4 \u0026plusmn; 11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.4 \u0026plusmn; 14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (gender)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (69.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (81.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.3 \u0026plusmn; 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.2 \u0026plusmn; 5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.963\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (22.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (22.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (55.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPACHE II score at day 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 \u0026plusmn; 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.9 \u0026plusmn; 7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score at day 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 \u0026plusmn; 3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3 \u0026plusmn; 3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.221\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score at day 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1 \u0026plusmn; 4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7 \u0026plusmn; 3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score at day 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9 \u0026plusmn; 4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.6 \u0026plusmn; 3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data at day 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.7 \u0026plusmn; 7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.5 \u0026plusmn; 6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.436\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.8 (81.4\u0026ndash;93.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86.4 (76.5\u0026ndash;91.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.9\u0026ndash;9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4 (3.8\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil/lymphocyte ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.1 (8.4\u0026ndash;32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9 (7.9\u0026ndash;24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.7 \u0026plusmn; 2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.1 \u0026plusmn; 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153.2 \u0026plusmn; 112.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185 \u0026plusmn; 98.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8 (0.5\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1 (0.6\u0026ndash;2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (total) (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5 (0.3\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4 (0.3\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.5 (11.6\u0026ndash;20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5 (7.6\u0026ndash;14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129.9 (60.1\u0026ndash;197.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115.3 (47.3\u0026ndash;180.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcalcitonin (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1 (0.4\u0026ndash;8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8 (0.3\u0026ndash;16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.836\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6 (pg/mL) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (12.5\u0026ndash;215.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.3 (12.5\u0026ndash;124.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood cadmium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 \u0026plusmn; 0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7 \u0026plusmn; 0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 \u0026plusmn; 0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.718\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine cadmium/creatinine (\u0026micro;g/g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 \u0026plusmn; 29.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5 \u0026plusmn; 1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.3 (6.7\u0026ndash;21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3 (1.4\u0026ndash;3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine nickel (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emean \u0026plusmn; SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.6 \u0026plusmn; 7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 \u0026plusmn; 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.2 (1.4\u0026ndash;4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.9 (1.4\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159.4 \u0026plusmn; 62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185.3 \u0026plusmn; 92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, count or median (interquartile range)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eAPACHE\u003c/em\u003e Acute Physiology and Chronic Health Evaluation, \u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eCRP\u003c/em\u003e C-reactive protein, \u003cem\u003eFiO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e fraction of inspired oxygen, \u003cem\u003eIL\u003c/em\u003e interleukin, \u003cem\u003eIQR\u003c/em\u003e interquartile range, \u003cem\u003ePaO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e partial pressure of oxygen in arterial blood, \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eSOFA\u003c/em\u003e Sequential Organ Failure Assessment, \u003cem\u003eWBC\u003c/em\u003e white blood cells\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003eAvailable for 155 ARDS patients\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe high-level group was older and had significantly lower BMI (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). SOFA scores were higher in the high urinary cadmium/creatinine group, reaching the level of significance at day 3 and day 7 after ARDS onset. No significant difference in smoking history was observed between the two groups. IL-6 levels were significantly higher in the high urinary cadmium/creatinine group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034).\u003c/p\u003e \u003cp\u003eBlood and urinary cadmium concentrations were both significantly higher in the high urinary cadmium/creatinine group (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas no significant difference was observed in blood or urinary nickel values. Patients in the high urinary cadmium/creatinine group faced a significantly higher risk of hypoxemia (i.e. lower PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes of ARDS patients by urinary cadmium/creatinine level\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, 28-, 60-, 90-day, and all-cause hospital mortality rates were significantly higher in the high urinary cadmium/creatinine group (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This group also had a higher incidence of shock and using inotropic agents. No significant differences were observed between two groups in terms of new-onset acute kidney injury, renal replacement therapy, duration of mechanical ventilator, length of ICU stay, or length of hospital stay.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes of ARDS patients stratified by urinary cadmium/creatinine levels\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUrinary cadmium/creatinine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;105)\u003c/p\u003e \u003cp\u003e(\u0026gt;\u0026thinsp;4.55 \u0026micro;g/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;76)\u003c/p\u003e \u003cp\u003e(\u0026le;\u0026thinsp;4.55 \u0026micro;g/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28-day hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (34.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60-day hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (46.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-day hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (51.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll cause hospital mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (52.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShock status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (72.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInotropic agents use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (78.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.864\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal replacement therapy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (16.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.403\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of mechanical ventilator (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (10\u0026ndash;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (9\u0026ndash;32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of ICU stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (13\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (12\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (21\u0026ndash;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (20\u0026ndash;51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.421\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, count (%) or median (interquartile range)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eICU\u003c/em\u003e intensive care unit\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Excluded participants with end-stage renal disease requiring maintenance hemodialysis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with hospital mortality in ARDS patients\u003c/h2\u003e \u003cp\u003eAfter adjusting for significant confounding parameters, multivariable logistic regression models revealed a number of factors that were positively correlated with hospital mortality in ARDS patients: lower BMI, current smoking, immunocompromised status, higher SOFA score, and higher urinary cadmium/creatinine.\u003c/p\u003e \u003cp\u003eARDS patients with high urinary cadmium/creatinine values faced a significantly higher odds of hospital mortality (adjusted OR 1.031, [95% CI 1.001\u0026ndash;1.062], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045). Among the studied variables, a urinary cadmium/creatinine value of \u0026gt;\u0026thinsp;4.55 \u0026micro;g/g had the greatest predictive value and was independently associated with hospital mortality (adjusted OR 2.365, [95% CI 1.003\u0026ndash;5.578], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The 90-day survival rate was significantly higher in the low urinary cadmium/creatinine value group (\u0026le;\u0026thinsp;4.55 \u0026micro;g/g) than in the high urinary cadmium/creatinine group (\u0026gt;\u0026thinsp;4.55 \u0026micro;g/g) (69.7% vs. 48.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, log-rank test) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable logistic regression analysis of factors associated with hospital mortality in ARDS patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariable analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariable analysis model 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eMultivariable analysis model 2\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (with each year increase)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.002 (0.980\u0026ndash;1.024)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.867 (0.804\u0026ndash;0.935)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.869 (0.787\u0026ndash;0.959)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.868 (0.783\u0026ndash;0.963)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.581 (0.845\u0026ndash;2.959)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (current)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.975 (0.977\u0026ndash;3.992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.827(1.026\u0026ndash;7.786)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (former)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.199 (0.848\u0026ndash;1.696)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (never)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.778 (0.637\u0026ndash;0.950)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic lung disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.567 (0.265\u0026ndash;1.216)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunocompromised status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.978 (1.618\u0026ndash;5.480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.369 (1.063\u0026ndash;5.276)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.298 (1.176\u0026ndash;1.434)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.323 (1.172\u0026ndash;1.492)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.203 (1.054\u0026ndash;1.374)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil/lymphocyte ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.016 (1.005\u0026ndash;1.027)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.825 (0.706\u0026ndash;0.965)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.994 (0.991\u0026ndash;0.998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.071 (0.950\u0026ndash;1.208)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.020 (0.988\u0026ndash;1.053)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.997 (0.993\u0026ndash;1.001)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood nickel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.392 (0.026\u0026ndash;5.841)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.497\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood cadmium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.009 (0.560\u0026ndash;1.816)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine nickel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.013 (0.970\u0026ndash;1.058)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine cadmium/creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.037 (1.010\u0026ndash;1.065)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.031 (1.001\u0026ndash;1.062)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine cadmium/creatinine\u0026thinsp;\u0026gt;\u0026thinsp;4.55 \u0026micro;g/g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.587 (1.388\u0026ndash;4.821)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.365 (1.003\u0026ndash;5.578)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003eARDS\u003c/em\u003e acute respiratory distress syndrome, \u003cem\u003eCI\u003c/em\u003e confidence interval, \u003cem\u003eFiO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e fraction of inspired oxygen, \u003cem\u003eOR\u003c/em\u003e odds ratio, \u003cem\u003ePaO\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e partial pressure of oxygen in arterial blood, \u003cem\u003eSOFA\u003c/em\u003e Sequential Organ Failure Assessment\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eFor the continuous variables, the odds ratio indicates that the odds of hospital mortality increases or decreases per unit increase of these variables\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1: add urine cadmium/creatinine as a continuous variable\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 2: add urine cadmium/creatinine\u0026thinsp;\u0026gt;\u0026thinsp;4.55 \u0026micro;g/g as a categorical variable\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe principle finding of this study is that urinary cadmium levels at ARDS onset were independently and positively associated with hospital mortality, and could be a valuable early prognostic indicator.\u003c/p\u003e \u003cp\u003eCadmium and nickel are considered environmental immunotoxicants. Cadmium is a cumulative toxin, whereas nickel is not. Chronic cadmium exposure almost invariably produces toxic or carcinogenic effects, with the kidney being the primary target organ. Cadmium elimination is slow, with retention predominantly in renal tubular cells. Its biological half-life is 75\u0026ndash;128 days in blood and 6\u0026ndash;38 years in renal tissue. Thus, urinary cadmium concentrations are generally treated as an indicator of chronic exposure and total body load, whereas blood concentrations serve as an indicator of acute or recent exposure [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExposure to cadmium or nickel can alter gene regulation, disrupt redox balance, elicit ROS accumulation, trigger oxidative stress, impair antioxidant defense systems, induce endoplasmic reticulum stress, instigate mitochondrial apoptosis, autophagy and thereby amplify inflammation and immunotoxicity\u0026mdash;of which can have a detrimental effect on body tissues and organ systems [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChronic cadmium exposure can aggravate oxidative stress, airway inflammation, and lung injury, making it a risk factor for more severe disease in conditions such as lower respiratory tract infections [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Oxidative stress and cytokine storm play central roles in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, driving dysregulated inflammation, immune activation, endothelial injury, immunothrombosis, tissue damage, and multiorgan dysfunction [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A number of recent studies have reported correlations between urinary cadmium levels and the severity and clinical outcomes of COVID-19 [\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our recent report, patients with severe COVID-19 who were in the highest quartile of urinary cadmium-to-creatinine ratio exhibited a significantly higher risk of all-cause hospital mortality [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOxidative stress is also central to the pathophysiology of ARDS, causing injury to alveolar epithelial and capillary endothelial cells as well as increased alveolar capillary barrier permeability, impaired gas exchange, and dysregulation of both local (i.e., alveolar) and systemic inflammation and immune activation [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Cadmium and nickel exposure may exacerbate these processes, but prior to this study, their roles in ARDS pathophysiology and outcomes had not been examined.\u003c/p\u003e \u003cp\u003eIn our cohort, we observed higher urinary cadmium values in ARDS patients than in ICU control patients. We also observed significantly higher values for inflammatory markers, including the neutrophil to lymphocyte ratio, CRP, and IL-6. Compared with ICU control patients, ARDS patients presented a significantly elevated risk of organ failure (i.e., higher APACHE II and SOFA scores) and hospital mortality (43.1% vs. 18.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e \u003cp\u003eCompared with survivors of ARDS, non-survivors exhibited significantly elevated concentrations of urinary cadmium, neutrophil to lymphocyte ratios, and APACHE II and SOFA scores. Multivariable regression analysis confirmed that urinary cadmium/creatinine was independently associated with hospital mortality in ARDS patients (adjusted OR 1.031, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045).\u003c/p\u003e \u003cp\u003eOur above findings suggest that high urinary cadmium concentrations, indicative of cadmium bioaccumulation, can exacerbate the effects of oxidative stress and dysregulated inflammatory responses during the course of ARDS, contributing to apoptosis, tissue injury, and organ dysfunction. Moreover, high urinary cadmium levels can increase the susceptibility of critically ill patients to developing ARDS, following predisposing factors such as sepsis and pneumonia, and an elevated risk of mortality among ARDS patients. Urinary cadmium could therefore be regarded as a prognostic biomarker.\u003c/p\u003e \u003cp\u003eAmong ARDS patients, those in the high urinary cadmium/creatinine group had significantly higher IL-6 values and a higher risk of hypoxemia (i.e. lower PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e). The high urinary cadmium/creatinine group had significantly higher 28-, 60-, 90-day, and all-cause hospital mortality. Note that urinary cadmium concentration is a surrogate marker of chronic cadmium exposure and lifetime accumulation, indicating that these ARDS patients were prone to the effects of cadmium, including oxidative stress, persistent inflammation, impaired gas exchange, and even an increased risk of mortality.\u003c/p\u003e \u003cp\u003eIn contrast, blood cadmium and nickel, and urinary nickel concentrations\u0026mdash;reflecting recent exposure\u0026mdash;did not differ significantly between ARDS and control patients or between survivors and non-survivors. Moreover, we analyzed cadmium concentrations in the BAL fluid (i.e., the local alveolar environment) of 57 ARDS patients and found no significant difference between survivors and non-survivors. This suggests that long-term cadmium accumulation is of greater relevance than short-term cadmium exposure or cadmium levels in the local environment in predicting the risk and prognosis of ARDS.\u003c/p\u003e \u003cp\u003eSmoking is a major cadmium source and is known to impair antioxidant systems, increase ROS burden, induce oxidative stress, and predispose the lungs to acute injury following triggers such as sepsis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. One prospective multicenter cohort study developed a lung injury prediction score that identified smoke inhalation as the predisposing condition most strongly correlated to acute lung injury [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Another prospective study reported that smoking is a risk factor for ARDS [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. One systematic review and meta-analysis concluded that smoking increased the risk of ARDS [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In the current study, the proportion of patients with a current and former history of smoking were higher in the ARDS group than in the ICU control group, although the difference did not reach the level of significance. Moreover, smoking history differed significantly between survivors and non-survivors of ARDS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039), and current smoking history was independently associated with hospital mortality (adjusted OR 2.827, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.044). Thus, it is reasonable to speculate that chronic cigarette smoking may be the primary source of chronic cadmium exposure in our ARDS patients, potentially amplifying oxidative stress and accelerating inflammation during the course of ARDS, thereby contributing to increased hospital mortality.\u003c/p\u003e \u003cp\u003eThis study was subject to several limitations, which should be considered in the interpretation of our findings. First, this cohort study was conducted at a single tertiary care referral center in Taiwan, such that the results are not necessarily generalizable to other institutions. Second, while urinary cadmium levels were corrected for creatinine to account for urine dilution, urinary nickel values were not routinely creatinine-corrected in our institution. Third, our analysis did not investigate the extent of oxidative stress biomarkers, such as the imbalance between ROS production and antioxidant enzymes, including superoxide dismutase and glutathione peroxidase. Fourth, as a prospective observational study, causality cannot be established. Finally, this study did not explore the molecular mechanisms of heavy metal\u0026ndash;induced lung injury, and the precise pathophysiology of ARDS warrants further mechanistic and experimental studies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eExposure to environmental cadmium may increase susceptibility to ARDS in critically ill patients, and has prognostic value in established ARDS cases. In our cohort, urinary cadmium concentrations at ARDS onset were independently associated with hospital mortality. These findings underscore the need for public health policies to reduce chronic cadmium exposure, which may lower ARDS incidence and improve outcomes. Elucidating the molecular mechanisms of heavy metal\u0026ndash;mediated lung injury will be crucial for developing prognostic biomarkers and targeted therapies for ARDS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPACHE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute Physiology and Chronic Health Evaluation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBAL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebronchoalveolar lavage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOVID-19\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronavirus disease 2019\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterleukin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereactive oxygen species\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esequential organ failure assessment.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki\u0026nbsp;after receiving approval from the Institutional Review Board for Human Research of Chang Gung Memorial Hospital (CGMH IRB No.\u0026nbsp;202100595A3, 202201833A3, and 202300897A3), and informed consent from all study participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used or analyzed in the study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn behalf of all authors, the corresponding author states that there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from Chang Gung Memorial Hospital (CMRPG3L0821, CMRPG3L0822, CORPG3M0331, and CMRPG3N1121), the Taiwan Ministry of Science and Technology (MOST 111-2314-B-182A-148), and the\u003c/p\u003e\n\u003cp\u003eTaiwan National Science and Technology Council (NSTC114-2314-B-182-065-).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLCC and THY assume responsibility for the accuracy of the data analysis and drafting of the manuscript. LCC, HHL, HWK, PCH, CSL, and THY performed the study design and data acquisition. LCC, TMC, and SCHK were responsible for statistical analysis of data. LCC, HHL, HWK and THY interpretation the results. All authors contributed to the completion of the manuscript and have approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their appreciation for the patients and staff in the general wards and ICU at Chang Gung Memorial Hospital, Linkou branch, Taiwan.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMatthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet. 2022;400(10358):1145\u0026ndash;1156.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQadir N, Sahetya S, Munshi L, Summers C, Abrams D, Beitler J, et al. An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2024;209(1):24\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBennett RM, Reilly JP. Environmental Risk Factors for Acute Respiratory Distress Syndrome. Clin Chest Med. 2024;45(4):797\u0026ndash;807.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShetty SS, D D, S H, Sonkusare S, Naik PB, Kumari N S, et al. Environmental pollutants and their effects on human health. Heliyon. 2023;9(9):e19496.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGutman L, Pauly V, Orleans V, Piga D, Channac Y, Armengaud A, et al. Long-term exposure to ambient air pollution is associated with an increased incidence and mortality of acute respiratory distress syndrome in a large French region. Environ Res. 2022;212(Pt D):113383.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReilly JP, Zhao Z, Shashaty MGS, Koyama T, Jones TK, Anderson BJ, et al. Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis. Intensive Care Med. 2023;49(8):957\u0026ndash;965.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoyama H, Kamogashira T, Yamasoba T. Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies. Antioxidants (Basel). 2024;13(1):76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJomova K, Alomar SY, Nepovimova E, Kuca K, Valko M. Heavy metals: toxicity and human health effects. Arch Toxicol. 2025;99(1):153\u0026ndash;209.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHossein-Khannazer N, Azizi G, Eslami S, Alhassan Mohammed H, Fayyaz F, Hosseinzadeh R, et al. The effects of cadmium exposure in the induction of inflammation. Immunopharmacol Immunotoxicol. 2020;42(1):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharkiewicz AE, Omeljaniuk WJ, Nowak K, Garley M, Nikliński J. Cadmium Toxicity and Health Effects-A Brief Summary. Molecules. 2023;28(18):6620.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Hassan MF, Ali W, Zou H, Liu Z, Ma Y. Effects of Cadmium Pollution on Human Health: A Narrative Review. Atmosphere. 2025; 16(2):225.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRasin P, Ashwathi AV, Basheer SM, Haribabu J, Santibanez JF, Garrote CA, Arulraj A and Mangalaraja RV. Exposure to cadmium and its impacts on human health: a short review. Journal of Hazardous Materials Advances. 2025;17;100608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkalny AV, Lima TRR, Ke T, Zhou JC, Bornhorst J, Alekseenko SI, et al. Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases. Food Chem Toxicol. 2020;146:111809.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiu LC, Lee CS, Hsu PC, Li HH, Chan TM, Hsiao CC, et al. Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study. Environ Health. 2024;23(1):29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaumert BO, Wang H, Samy S, Park SK, Lam CN, Dunn K, et al. Environmental pollutant risk factors for worse COVID-19 related clinical outcomes in predominately hispanic and latino populations. Environ Res. 2024;252(Pt 4):119072.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng HL, Zhang B, Wang X, Yang Q, Cheng L. Urinary trace elements in association with disease severity and outcome in patients with COVID-19. Environ Res. 2021;194:110670.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBezerra FS, Lanzetti M, Nesi RT, Nagato AC, Silva CPE, Kennedy-Feitosa E, Melo AC, Cattani-Cavalieri I, Porto LC, Valenca SS. Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries. Antioxidants (Basel). 2023;12(3):548.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim EY, Lee SY, Shin HS, Kim GD. Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome. Antioxidants (Basel). 2023;12(11):2016.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang F, Ge R, Cai Y, Zhao M, Fang Z, Li J, Xie C, Wang M, Li W, Wang X. Oxidative stress in ARDS: mechanisms and therapeutic potential. Front Pharmacol. 2025;16:1603287.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526\u0026ndash;2533.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo H, Liu H, Jian Z, Cui H, Fang J, Zuo Z, et al. Immunotoxicity of nickel: Pathological and toxicological effects. Ecotoxicol Environ Saf. 2020;203:111006.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGenchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: Human Health and Environmental Toxicology. Int J Environ Res Public Health. 2020;17(3):679.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYin H, Wang C, Guo H, Li X, Liu J. The mechanism of nickel-induced autophagy and its role in nephrotoxicity. Ecotoxicol Environ Saf. 2024;273:116150.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark SK, Sack C, Sir\u0026eacute;n MJ, Hu H. Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults. Environ Health Perspect. 2020;128(12):127004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarson-Casey JL, Liu S, Pyles JM, Lapi SE, Saleem K, Antony VB, Gonzalez ML, Crossman DK, Carter AB. Impaired PPARγ activation by cadmium exacerbates infection-induced lung injury. JCI Insight. 2023;8(9):e166608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlam MS, Czajkowsky DM. SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities. Cytokine Growth Factor Rev. 2022;63:44\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWieczfinska J, Kleniewska P, Pawliczak R. Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections. Oxid Med Cell Longev. 2022;2022:5589089.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGain C, Song S, Angtuaco T, Satta S, Kelesidis T. The role of oxidative stress in the pathogenesis of infections with coronaviruses. Front Microbiol. 2023;13:1111930.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeo YS, Park JM, Kim JH, Lee MY. Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants (Basel). 2023;12(9):1732.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGajic O, Dabbagh O, Park PK, Adesanya A, Chang SY, Hou P, et al; U.S. Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med. 2011;183(4):462\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoazed F, Hendrickson C, Jauregui A, Gotts J, Conroy A, Delucchi K, et al. Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers. Am J Respir Crit Care Med. 2022;205(8):927\u0026ndash;935.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Xu J, Li Y, Meng F, Wang W. Smoking on the risk of acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care. 2024;28(1):122.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cadmium, Nickel, Acute respiratory distress syndrome, Oxidative stress, Outcomes, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-9086457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9086457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCadmium and nickel exposure has been shown to induce oxidative stress, exacerbate inflammation, and trigger immunotoxicity—all of which may play central role in the pathophysiology of acute respiratory distress syndrome (ARDS). This study investigated association between cadmium and nickel exposures and the severity of ARDS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective observational study enrolled critically ill patients with or without ARDS who had been admitted to an intensive care unit (ICU) in Taiwan between November 2021 and April 2025. Clinical outcomes were compared with cadmium and nickel concentrations in blood and urine, measured within 3 days after ARDS onset (ARDS patients) or within 3 days after ICU admission (control subjects).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 181 patients with ARDS and 49 ICU control subjects were included. The overall in-hospital mortality rate of ARDS patients was 43.1%. Urinary cadmium concentrations were significantly higher in ARDS patients than in ICU control patients. Among ARDS patients, non-survivors had significantly higher urinary cadmium/creatinine values, higher neutrophil/lymphocyte ratios, and a higher risk of organ failure (i.e., higher APACHE II and SOFA scores) (all \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). ARDS patients with elevated urinary cadmium/creatinine values (\u0026gt; 4.55 µg/g; 105 patients; 58%) faced a significantly higher risk of organ failure (i.e., higher SOFA scores), interleukin-6 values, risk of hypoxemia (i.e., lower PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e), and 28-, 60-, 90-day, and all-cause hospital mortality, compared to those with low of urinary cadmium/creatinine values (≤ 4.55 µg/g; 76 patients; 42%) (all \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). Multivariable logistic regression models revealed that urinary cadmium/creatinine levels were independently associated with hospital mortality (adjusted OR 1.031 [95% CI 1.001–1.062], \u003cem\u003ep\u003c/em\u003e = 0.045), and that a urinary cadmium/creatinine value \u0026gt; 4.55 µg/g had the greatest predictive value (adjusted OR 2.365, [95% CI 1.003–5.578], \u003cem\u003ep\u003c/em\u003e = 0.049).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElevated urinary cadmium concentration in the early course of ARDS is independently associated with increased hospital mortality.\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e","manuscriptTitle":"Correlation between urinary cadmium concentrations and hospital mortality in acute respiratory distress syndrome: a prospective observational cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 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