Time trends in mortality and ventilatory support among women with acute respiratory failure in a respiratory ICU: a 12-year retrospective cohort study”

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While women generally show a survival advantage in the general population, this is not consistently observed in critical care. Long-term temporal trends in women admitted to the ICU, especially during the COVID-19 pandemic, remain poorly characterized. Methods We performed a retrospective cohort study of women with acute respiratory failure admitted to a tertiary respiratory ICU in Türkiye between 2013 and 2024. Demographics, comorbidities, severity score (APACHE II), admission diagnoses, and ventilatory support modalities were analyzed. The primary outcome was ICU mortality. Secondary outcomes included annual trends in female representation, ventilatory practices, and case mix. Joinpoint regression was used to calculate annual percent change (APC) and identify significant temporal shifts, including the pandemic period. Results Among 17,670 ICU admissions, 5,712 (32.3%) were women. Female admission declined until 2017 (31%) but increased thereafter, reaching 43% in 2024 (APC + 3.4%, p = 0.003). Pneumonia admissions rose from 10% in 2013 to 26% in 2024, whereas COPD remained stable. Ventilatory support shifted substantially: NIV declined after 2018 (APC − 11.1%, p = 0.01), IMV increased after 2021 (66% in 2024), and oxygen therapy alone rose steadily (42% in 2024). NIV and IMV application peaked in 2016 (25%), decreased during 2020–2021, then increased after 2022. Female mortality decreased until 2019 but increased thereafter (APC + 11.6%, p = 0.01), diverging from male mortality, which declined after 2021. Conclusion Female ICU representation and case mix changed significantly over the study period, with pneumonia and evolving ventilatory practices contributing to rising mortality after the pandemic. These findings underscore the importance of incorporating sex- and gender-specific considerations into critical care research and practice. intensive care unit women sex differences ventilatory support pneumonia COVID-19 mortality Figures Figure 1 Figure 2 Figure 3 Key Findings Female representation increased after the pandemic. The proportion of women among ICU admissions declined until 2017 but reversed afterwards, showing a continuous increase and reaching 43% in 2024. Notably, this upward trend accelerated after the COVID-19 pandemic (2020–2022), suggesting that sex-specific patterns of ICU admission may have been influenced by pandemic-related case mix. Ventilatory support strategies shifted markedly during and after the pandemic. Non-invasive ventilation (NIV), which dominated prior to 2018 (peak 72% in 2016), declined substantially during the pandemic years. At the same time, invasive mechanical ventilation (IMV) use increased sharply, especially after 2021, peaking at 66% in 2024. Oxygen therapy alone also rose steadily throughout the period, with its most pronounced increase occurring during and after the pandemic, reaching 42% in 2024. Case mix changes were driven by pneumonia in the pandemic era. Pneumonia admissions in women showed a strong upward trend from 2013 onwards, but the sharpest rise occurred during and after the pandemic, when pneumonia became the predominant admission diagnosis (26% in 2024). In contrast, COPD admissions remained relatively stable or declined in recent years. Female mortality increased during the pandemic, while male mortality decreased afterward. Female ICU mortality, which had been declining until 2019, rose significantly from 2019 onwards, reaching 43% in 2024. Conversely, male mortality decreased after 2021, resulting in a divergence between sexes. This suggests that the pandemic had a disproportionate adverse impact on female ICU outcomes. NIV failure patterns shifted around the pandemic. NIV failure was highest before the pandemic (25% in 2016), decreased to its lowest levels during the early pandemic period (~10–13% in 2020–2021), but then rebounded dramatically after 2022. This pattern indicates that escalation strategies for ventilatory support may have been altered during the pandemic and adjusted again in the post-pandemic period. Introduction Sex differences in critical care outcomes have been increasingly recognized over the past two decades. Women generally have a survival advantage over men in the general population; however, this advantage is not consistently observed in the intensive care unit (ICU) setting, where disease severity, treatment strategies, and access to care may influence outcomes [ 1 ]. Epidemiological studies have shown that men are more frequently admitted to ICUs than women, even after adjusting for severity of illness and comorbidities, suggesting potential disparities in referral or triage practices [ 1 , 2 ]. In large international cohorts, the proportion of female ICU patients typically ranges from 30% to 40%, and mortality rates are variably reported as lower, similar, or higher compared to males depending on the underlying diagnosis and treatment received [ 2 , 3 ]. In acute respiratory failure (ARF), sex-based physiological differences—including lung size, airway diameter, and respiratory muscle strength—may impact ventilatory support tolerance and outcomes [ 4 ]. Furthermore, practice-related factors, such as underestimation of women’s height leading to higher delivered tidal volumes, have been associated with increased ventilator-induced lung injury risk in females [ 4 , 5 ]. Despite extensive research on sex differences in ICU outcomes, temporal trends in female mortality, particularly in respiratory ICUs, remain poorly characterized. Most existing studies have been cross-sectional or limited to short observation periods, providing little insight into long-term changes [ 2 , 3 ]. Evidence regarding the impact of pandemics or large-scale viral outbreaks on sex-specific ICU mortality is scarce, and findings are inconsistent; for example, some reports suggest higher male mortality during COVID-19, while others have observed equal or higher mortality in women depending on comorbidities and care access [ 6 , 7 ]. The relationship between ventilatory support modality and sex-specific outcomes also remains debated. In acute respiratory distress syndrome (ARDS), studies have generally reported similar mortality between sexes, yet practice-related factors such as suboptimal protective ventilation in women could mask true differences [ 4 , 5 ]. Moreover, the influence of changing case mix—such as pneumonia and chronic obstructive pulmonary disease (COPD) prevalence—on sex-specific mortality over time has not been well studied [ 2 , 8 ]. Given these uncertainties, we aimed to investigate sex-specific trends in ICU admissions, ventilation practices, and mortality among women with acute respiratory failure in a respiratory intensive care unit over a 12-year period. Using joinpoint regression, we sought to identify significant changes in annual percent change (APC) for overall ICU female representation, invasive and non-invasive ventilation use, and mortality before and after the COVID-19 pandemic. We hypothesized that female mortality trends would not parallel those of males, with a possible increase during the pandemic period, and that shifts in ventilation strategies and case mix—particularly pneumonia and COPD prevalence—might contribute to these trends. Present study allows the examination of long-term mortality trends, case mix, and ventilation practices in women admitted to a respiratory ICU over a 12-year period. Methods Study design and setting We conducted a retrospective cohort study of female patients admitted to the university respiratory intensive care unit. The ICU is a tertiary referral center specialized in respiratory failure management. The study center ICU beds number are 24 to 60 during 12 years-period. Intensive care physicians are the same physicians throughout their working hours and provide subspecialty training in intensive care at an academic center. It is the largest intensive care center in the country for respiratory diseases. A team of academic physicians works 24/7. All medical decisions are made according to pre-established protocols. All ICU protocols are organized according to international and national guidelines. The entire ICU team adheres to these rules. The study period extended from January 2013 to December 2024, covering 12 consecutive years, including the COVID-19 pandemic era. Patients All adult patients (≥ 18 years) admitted to the respiratory ICU with ARF [ 9 ] were screened. Female patients were included in the analysis, while male patients were retained for comparative purposes in exploratory analyses. The exclusion criteria were ICU admissions for postoperative monitoring without ARF, readmissions within the same hospitalization, and missing key outcome data. For each patient, demographic information, comorbidities, and severity scores at admission were recorded. Data collection Clinical data were extracted from electronic medical records and ICU databases. Variables included: demographics, age, sex, co-morbid diseases as chronic obstructive pulmonary disease (COPD) [ 10 ], reason of ARF as pneumonia [ 11 ]. ICU severity indices: Acute Physiology and Chronic Health Evaluation II (APACHE II) score [ 12 ]. Ventilatory support: use of non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), NIV and IMV together, oxygen therapy alone was recorded. The indication and application of NIV, IMV and oxygen therapy alone were well-defined according to ARF guidelines [ 9 ]. The sedation [ 1 ], NIV [ 14 ], IMV, weaning from mechanical ventilation [ 15 ], oxygen therapy-high flow nasal canula [ 16 ] application were well-defined. The study outcomes: The primary outcome was ICU mortality among women with ARF. Secondary outcomes included annual trends in female representation among ICU admissions, distribution of admission diagnoses, type of ventilatory support used, NIV-IMV rates, COPD co-morbid disease annual changing, pneumonia ration annually. Statistical analysis Continuous variables were summarized as mean (standard deviation) or median (1st and 3rd quartile), and categorical variables as counts (percentages). Between-group comparisons (female vs. male patients; survivors vs. non-survivors) were performed using Z- test [ 17 ]. Temporal trends in ICU female admissions, ventilatory support, and mortality were analyzed using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Joinpoint analysis identified statistically significant changes in trends over time, particularly before and after the COVID-19 pandemic. A two-sided p value < 0.05 was considered statistically significant. All analyses were conducted using SPSS (IBM Corp., Armonk, NY, USA) and Joinpoint Regression Program (National Cancer Institute, USA) [ 18 ]. Results Baseline characteristics of female ICU patients Between 2013 and 2024, a total of 17,670 patients were admitted to the respiratory ICU, of whom 5,712 (32.3%) were women. The percentage of female admissions varied over time, ranging from 31% in 2017 to a peak of 43% in 2024. The mean age of female patients remained consistently high across the study period, with a median ranging from 68 to 73 years. Age distribution did not show major annual variation, although a slight upward trend was observed after 2020. Severity of illness, as measured by the APACHE II score, was stable over time, with median values generally between 20 and 25 (1st and 3rd quartile 16–30). No significant shifts in severity were observed across the pre-pandemic and pandemic periods. The percentage of women admitted with COPD as a co-morbid disease ranged from 7–13% during 2013–2019, stabilizing around 10–12% after 2020. In contrast, pneumonia-related admissions increased substantially, from 10–11% in 2013–2015 to 22–26% between 2018 and 2024. The highest burden of pneumonia was recorded in 2024 (26%), coinciding with the post-pandemic period (Table 1) Table 1. Annual number of patients admitted to intensive care and age and severity scores of female patients with pneumonia and chronic obstructive pulmonary disease ICU¶ Beds, N Patients, N Female N (%) Age APACHE II* COPD, N (%)# Pneumonia, N (%) 24 1031 387 (38) 68 (15) 22 (19-29) 69 (7) 101 (10) 24 1019 372 (37) 70 (14) 23 (20-29) 66 (7) 116 (11) 24 1228 435 (35) 68 (14) 24 (20-29) 113 (9) 138 (11) 24 1222 421 (35) 70 (15) 25 (20-30) 148 (12) 177 (15) 24 1233 381 (31) 70 (14) 25 (20-30) 138 (11) 192 (16) 24 1320 450 (34) 69 (15) 22 (18-28) 172 (13) 293 (22) 26 1314 426 (32) 71(14) 22 (18-27) 175 (13) 235 (18) 26 1624 566 (35) 69 (16) 20 (16-24) 190 (12) 356 (22) 60 1981 684 (35) 69 (15) 20 (16-24) 236 (12) 452 (23) 60 2439 896 (37) 73 (14) 21 (17-26) 252 (10) 578 (24) 32 1786 666 (37) 73 (14) 23 (18-29) 160 (9) 382 (21) 42 1473 627 (43) 73 (15) 25 (21-30) 183 (12) 377 (26) ¶ ICU: intensive care unit, *APACHE II: acute physiological and chronic health evaluation II, #COPD: chronic obstructive pulmonary diseases. Respiratory support in female patients Over the 12-year period, respiratory support strategies among women with ARF demonstrated substantial annual variation (Table 2). NIV was the predominant support modality in earlier years, reaching its highest use in 2016 (72%). During this period, women were significantly more likely than men to receive NIV ( p < 0.001). However, its utilization progressively declined, stabilizing at 44–48% during 2020–2024. IMV was less common among women in the early years (37–49% in 2013–2015) compared to men, but its use increased after the pandemic. By 2024, IMV was applied in 66% of female patients. NIV and IMV application together, the percentage of women requiring escalation from NIV to IMV ranged from 10–26%, with the highest rate in 2016 (25%). After 2020, this proportion declined to approximately 10–13%. The use of oxygen therapy without NIV or IMV rose significantly in the later years, from 8–10% in 2014–2016 to 42% in 2024. This increase was particularly evident during and after the COVID-19 pandemic (Table 2). Table 2. Annual numbers of female and male patients’ respiratory support comparison during a 12-year period in intensive care unit. All Invasive Mechanical Ventilation Non-invasive Mechanical Ventilation NIV and IMV Oxygen Therapy Alone Years N Female, N (%) Male, N (%) p value Female, N (%) Male, N (%) p value Female, N (%) Male, N (%) p value Female, N (%) Male, N (%) p value 2013 1031 143 (38) 334 (52) 0.005 256 (65) 472 (73) 0.024 72 (18) 189 (29) 0.071 58 (15) 87 (14) 0.88 2014 1019 176 (49) 356 (55) 0.19 252 (68) 415 (64) 0.29 93 (26) 196 (30) 0.48 30 (8) 90 (14) 0.39 2015 1228 202 (48) 448 (57) 0.033 310 (64) 526 (66) 0.66 109 (23) 230 (29) 0.25 52 (10) 70 (9) 0.85 2016 1222 267 (63) 371 (46) 0.081 429 (72) 372 (46) <0.001 154 (25) 167 (21) 0.40 54 (9) 79 (10) 0.85 2017 1233 181 (47) 412 (48) 0.82 252 (66) 450 (53) <0.001 89 (26) 209 (25) 0.86 56 (17) 160 (19) 0.74 2018 1320 196 (43) 404 (46) 0.49 308 (68) 538 (62) 0.08 108 (23) 193 (22) 0.84 82 (19) 177 (20) 0.85 2019 1314 161 (37) 397 (45) 0.083 275 (64) 536 (60) 0.27 77 (18) 200 (23) 0.37 94 (23) 202 (23) 0.99 2020 1624 186 (37) 377 (36) 0.82 248 (47) 436 (41) 0.13 63 (13) 132 (13) >0.99 199 (32) 403 (38) 0.15 2021 1981 194 (28) 425 (33) 0.21 326 (48) 546 (42) 0.085 70 (10) 128 (10) >0.99 263 (38) 514 (40) 0.59 2022 2439 337 (38) 586 (38) >0.99 428 (48) 695 (45) 0.33 90 (10) 160 (10) >0.99 232 (26) 439 (29) 0.41 2023 1786 240 (37) 364 (33) 0.31 287 (44) 468 (42) 0.59 81 (13) 116 (10) 0.51 231 (33) 424 (38) 0.20 2024 1473 407 (66) 583 (69) 0.32 418 (67) 599 (71) 0.17 267 (43) 402 (48) 0.20 272 (42) 402 (48) 0.13 IMV: invasive mechanical ventilation, NIV: noninvasive mechanical ventilation, Annual trends (Joinpoint analysis) Figure 1 shows the change in the proportion of female patients in the ICU over the years (Fig. 1 . a), the proportion of women admitted to the ICU with pneumonia (Fig. 1 . b), and the change in the presence of COPD as a comorbid disease over the years (Fig. 1 . c). Female representation declined between 2013–2017 (APC − 4.7%, p = 0.017) later years increased significantly until 2024 (APC + 3.4%, p = 0.003) (Fig. 1 . a). Pneumonia admissions rose markedly 2013–2018 (APC + 15.5%, p < 0.001), continuing at a slower pace thereafter (Fig. 1 . b). COPD as co-morbid disease increased from 2013–2018 (APC + 16.7%, p = 0.02) later years decreased until 2022, followed by a modest nonsignificant rebound (Fig. 1 . c). Figure 2 shows the use of IMV (Fig. 2 . a), NIV (Fig. 2 . b), combined NIV and IMV (Fig. 2 . c), and oxygen therapy alone (Fig. 2 . d) in female patients with respiratory failure over the years. Ventilatory support: IMV among women increased during 2013–2016 (APC + 14.8%, p = 0.006), declined during 2016–2021 (APC − 13.5%, p < 0.001), then surged sharply after 2021 (APC + 26.8%, p < 0.001) (Fig. 2 . a). NIV remained stable until 2018, declined significantly between 2018–2022 (APC − 11.1%, p = 0.01), then rebounded after 2022 (APC + 21.0%, p = 0.04) (Fig. 2 . b). NIV and IMV used initially rose, declined significantly from 2017–2022 (APC − 21.2%, p < 0.001), but escalated sharply after 2022 (APC + 109.2%, p < 0.001) (Fig. 2 . c). Oxygen therapy alone showed a continuous rise (APC + 15.1%, p = 0.0004), reaching 42% in 2024 (Fig. 2 . d). Figure 3 shows the change in mortality in female and male patients over the years. The changes in mortality rates female patients in the ICU over the years (Fig. 3 . a) and the changes in mortality rates among female patients over the years (Fig. 3 . b) are summarized. The changes in mortality rates male patients in the ICU over the years (Fig. 3 . c) and the changes in mortality rates among male patients over the years (Fig. 3 . d) are summarized. Female ICU mortality exhibited three phases: increase during 2013–2016 (APC + 9.8%, p = 0.04), decrease during 2016–2019 (APC − 12.2%, p = 0.03), and subsequent increase during 2019–2024 (APC + 11.6%, p = 0.01) (Fig. 3 a–b). In contrast, male ICU mortality remained stable from 2013–2021 (APC + 0.4%, NS), then declined significantly after 2021 (APC − 5.1%, p = 0.04) (Fig. 3 c). A separate model demonstrated fluctuation in male subgroup mortality with periods of increase, decline, and renewed rise (Fig. 3 d). Discussion In this 12-year cohort study of women admitted to a respiratory intensive care unit with acute respiratory failure, we identified the proportion of female admissions in 2013–2017 shows decline 38% to 31% increased significantly after 2017 to 2024, reaching its highest level after the COVID-19 pandemic 43% in 2024. NIV application in female patients is predominant respiratory support in 2013 to 2019 (64%-72%), declined during the pandemic years in 2020 to 2022 (47%-48%), while IMV least 28% (2021) in pandemic pre-post pandemic (38% − 60% respectively) and oxygen therapy in female patients show gradually increasing in 12 years (15% to 42%). The female patients with pneumonia admissions show the rising from 10% to 26% in 12-years. COPD in female patients show the increasing 7% to 13% during the study period, in 2013 to 2018, COPD increase 16% each year, a after 2018 to 2022 shows decrease nearly 8% annually. The female ICU mortality rates are 34% to 42% in 12 years and decrease 2% APC in 2013–2018, and increase after 2019 as 5.7% APC, the male mortality rates are 70%-57% and it shows, which declined after 2021 as 5% APC. Our findings on female ICU representation align with previous international reports indicating that women typically comprise 30–40% of ICU admissions [ 2 , 3 ]. However, the observed increase in female representation after 2017 contrasts with many earlier studies that reported stable or declining female proportions over time [ 1 ]. This rise may partly reflect shifts in case mix, particularly the growing burden of pneumonia, which disproportionately affected women during and after the COVID-19 pandemic [ 6 , 7 ]. Importantly, this increase suggests that sex-specific referral and triage dynamics may have evolved in recent years, possibly influenced by pandemic-related changes in healthcare utilization and disease epidemiology. The temporal changes we observed in ventilatory support among female patients are noteworthy. NIV was the dominant strategy prior to 2018, in line with established evidence demonstrating its benefits in acute exacerbations of COPD and selected cases of hypoxemic respiratory failure [ 19 , 20 ]. However, during the pandemic years, NIV use declined markedly, while IMV and oxygen therapy increased. This pattern mirrors global reports during COVID-19, where concerns about aerosolization risk and poor tolerance in severe hypoxemia led to earlier intubation and expanded use of high-flow oxygen therapy [ 16 , 21 ]. Interestingly, our analysis revealed that IMV utilization, once lower in female patients compared to men, rose sharply after 2021, narrowing sex-based differences in ventilatory management. Prior studies have suggested that female may be at higher risk of ventilator-induced lung injury due to underestimation of predicted body weight and inadvertent delivery of higher tidal volumes [ 4 , 5 ]. The rise in IMV use among female patients in our cohort may therefore carry clinical implications, potentially contributing to the parallel increase in female mortality observed after the pandemic. In present study Overall, sex-based differences were more pronounced in the earlier years, with women more frequently treated with NIV and less often with IMV. These disparities diminished during and after the pandemic period, when both IMV and oxygen therapy use increased substantially among women. The divergent mortality trends between female and male in our cohort are particularly striking. While female ICU mortality decreased until 2019, it increased significantly during and after the pandemic, reaching 43% in 2024. In contrast, male mortality remained stable until 2021 and then declined. These findings suggest that the COVID-19 pandemic may have disproportionately worsened outcomes in women. Earlier studies on sex differences in ICU mortality have reported inconsistent results. Large multinational cohorts, such as the ICON audit, found no overall survival advantage for women, although regional and diagnosis-specific differences were noted [ 2 , 3 ]. During the COVID-19 pandemic, several meta-analyses suggested that male sex was associated with higher mortality [ 6 ], yet others emphasized that outcomes were strongly influenced by comorbidities, treatment accessibility, and variations in care [ 7 ]. Our findings add nuance to this literature by demonstrating that, in a respiratory ICU population, female mortality increased after the pandemic, even as male mortality declined. Several mechanisms may underline this pattern. First, the observed rise in IMV utilization among female after 2021 may have contributed, as IMV is consistently associated with higher mortality in patients with hypoxemic respiratory failure. Second, the increasing burden of pneumonia among female patients could have shifted the case mix toward more severe and less reversible conditions. Third, practice-related factors—such as delays in escalation from NIV to IMV—may have amplified sex-specific risks during the pandemic. Changes in case mix also provide important context for our findings. Pneumonia became increasingly common among female admitted to the ICU, rising from approximately 10% in 2013 to over 25% in 2024. In present study the pneumonia in female patient’s annual average percent change 15.5% in 2013–2018 and 4.1% in 2018 to 2024. The pandemic period did not show further increased the pneumonia proportion in female patients. This trend was particularly pronounced during and after the COVID-19 pandemic, when viral and secondary bacterial pneumonias contributed to a substantial proportion of ICU admissions worldwide [ 8 , 21 ]. The increased burden of pneumonia among female patients may have been a major driver of the rising mortality observed in our cohort. By contrast, COPD exacerbations, a historically common cause of ICU admission, showed relative stability or even decline in recent years. This pattern is consistent with reports of improved outpatient management, vaccination strategies, and wider use of NIV in emergency settings [ 10 , 19 ]. The relative decline in COPD may also reflect the overshadowing impact of pneumonia and pandemic-related respiratory infections on ICU utilization. Together, these shifts suggest that the increasing predominance of pneumonia as a primary diagnosis has altered the sex-specific profile of ICU patients, disproportionately exposing female to high-mortality conditions. The dynamic patterns of NIV and IMV application observed in our study also warrant attention. NIV and IMV application rates in female patients peaked before the pandemic (25% in 2016), declined to their lowest levels during the early pandemic years (~ 10–13% in 2020–2021), and then increased sharply again after 2022. These findings suggest evolving practices in escalation strategies and highlight potential vulnerabilities in female patients. Previous studies have emphasized that delayed transition from NIV to IMV is associated with worse outcomes, particularly in patients with pneumonia or severe hypoxemia [ 22 , 23 ]. The temporary decline in NIV-IMV applications during the pandemic may reflect changes in ICU practice, including earlier intubation policies and greater reliance on high-flow oxygen therapy, which reduced the proportion of patients undergoing prolonged unsuccessful NIV trials [ 16 ]. However, the renewed increase in NIV and IMV after 2022 may indicate a reversion to pre-pandemic practices or reflect the challenges of managing an increasingly complex and older patient population. Importantly, sex-specific physiological differences may contribute to these trends. Women have smaller lung volumes and reduce respiratory muscle strength compared to men, factors that may predispose them to poorer tolerance of NIV support [ 4 ]. In addition, potential underestimation of women’s height when setting ventilator parameters could increase the risk of patient–ventilator asynchrony and ventilator-induced lung injury [ 5 ]. These mechanisms may partly explain why changes in ventilatory support strategies during the pandemic had disproportionate effects on female patients. In present study ventilator settings were managed by experienced team, pandemic period oxygen therapy was main respiratory support in our study. Limitations This study has several limitations. First, it was conducted in a single tertiary respiratory ICU, which may limit the generalizability of the findings to other settings with different patient populations or admission practices. Second, the retrospective design restricted our ability to assess certain key variables, such as detailed ventilator settings, timing of escalation from non-invasive to invasive ventilation, or adherence to sepsis management bundles, all of which could influence outcomes. Third, while joinpoint regression allowed us to detect significant temporal changes, the analysis cannot fully account for unmeasured confounders, such as socioeconomic factors, vaccination status, or outpatient management strategies that may have shifted over time. Fourth, the impact of the COVID-19 pandemic on ICU case mix and outcomes is complex and multifactorial; although our data captures these effects, the retrospective approach precludes causal attribution. However, certain mechanistic questions—such as the role of hormonal or genetic factors in pandemic-related mortality shifts, or the precise contribution of ventilator-induced lung injury to sex-specific outcomes—cannot be addressed with the available retrospective data. Similarly, we cannot directly assess quality-of-care indicators such as tidal volume accuracy, timing of escalation from non-invasive to invasive ventilation, or adherence to sepsis management bundles, which may be important mediators of observed trends. Meanwhile the study center and study team are well trained and experienced intensivist and they work 24/7 in ICU. Each unwanted event quickly and well managed. Finally, our study focused on ICU outcomes, and we were unable to provide long-term follow-up data, such as post-discharge survival or quality of life, which are particularly relevant for female patients. Conclusion In this 12-year cohort study of women admitted to a respiratory intensive care unit with acute respiratory failure, we identified several important temporal trends. First, the proportion of female admissions increased significantly after 2017, reaching its highest level after the COVID-19 pandemic. Second, ventilatory support strategies shifted markedly: non-invasive ventilation, once the predominant modality, declined during the pandemic years, while invasive mechanical ventilation and oxygen therapy became increasingly common. Third, the case mix of female patients changed, with pneumonia admissions rising steadily and becoming the leading diagnosis in the later years. Finally, mortality trends diverged by sex: female ICU mortality increased after 2019, in contrast to male mortality, which declined after 2021.These findings suggest that evolving case mix and ventilatory practices may have disproportionately affected women, underscoring the need for heightened attention to sex- and gender-related factors in critical care. Future multicenter studies are warranted to validate these trends and to explore tailored management strategies that could mitigate excess mortality in female ICU patients. Abbreviations ICU intensive care unit APACHE II acute physiologic and chronic health evaluation s ARDS acute respiratory distress syndrome COPD chronic obstructive pulmonary diseases APC changes in annual percent change COVID-19 Coronavirus disease-2019 ARF acute respiratory failure IMV invasive mechanical ventilation NIV non-invasive mechanical ventilation Declarations Declarations Ethics approval and consent to participate: The study was approved by the institutional ethics committee of University of Health Sciences, Ministry of Health Sureyyapaşa Chest Diseases Thoracic Surgery Teaching and Research Hospital Ethics Committee-Istanbul-Turkiye (approval number: 2024-78 date: 24/07/2025) and conducted in accordance with the Declaration of Helsinki. The requirement for signed informed consent was waived by the institutional ethics committee due to the retrospective real life observational design. and was deemed unnecessary according to national regulations Consent for publication: All authors agree with consent of publication. All of the material is owned by the authors and/or no permissions are required Competing Interests: I declare that the authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper. Clinical trial number not applicable. LEGENDS Tables Legends Table 1. Annual number of patients admitted to intensive care and age and severity scores of female patients with pneumonia and chronic obstructive pulmonary disease Table 2. Annual numbers of female and male patients’ respiratory support comparison during a 12-year period in intensive care unit. Funding: This research did not receive funding. Author Contribution All authors actively participated in the treatment of the cases at YBU, the collection of literature, the acquisition of data, the analysis, and the preparation of the article. Study design, writing manuscript: Author ÖYM, SG, NA, ZK, GG, BY, EAT, HBT, AB, CA, İEİ, DV, CS, FK, GED. Study analysis: ZK, SG, Data management: BY, CA, GED, HBT, AB, BY, İEİ, EAT, ÖYM, SG, NA, ZK, GG, Literature evaluation: FK, CS, DV, CA, BY, İEİ, HBT, AB, ZK. Acknowledgement We would like to express our sincere gratitude to all intensive care nurses and healthcare assistants who have worked in intensive care in 12-year period.The following in the manuscript: ‘Clinical trial number: not applicable. Human Ethics and Consent to Participate declarations: The study was approved by the institutional ethics committee of University of Health Sciences, Ministry of Health Sureyyapaşa Chest Diseases Thoracic Surgery Teaching and Research Hospital Ethics Committee (approval number: 2024-78 date: 24/07/2025) and conducted in accordance with the Declaration of Helsinki. The requirement for signed informed consent was waived by the institutional ethics committee due to the retrospective real life observational design and it was deemed unnecessary according to national regulationsThis research did not receive funding.'Availability of data and materials' statement, which is present in the main manuscript, on SYSTEM as well under Data Availability sub-section of Declaration section Data Availability The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Garland A. Improving the care of critically ill women. 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Am J Respir Crit Care Med. 2008;178(4):346–55. 10.1164/rccm.200710-1589OC . Peckham H, de Gruijter NM, Raine C, Radziszewska A, Ciurtin C, Wedderburn LR, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020;11(1):6317. 10.1038/s41467-020-19741-6 . Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020;588(7837):315–20. 10.1038/s41586-020-2700-3 . Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677–86. 10.1001/jama.2015.88 . American Thoracic Society/European Respiratory Society. Standards for the diagnosis and management of patients with acute respiratory failure. Am J Respir Crit Care Med. 1999;159:877–99. 10.1164/ajrccm.159.3.ATS . Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD. 2023 Report. Available from: https://goldcopd.org/2023-gold-report-2/ [cited 2025 Aug 17]. ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–8. 10.1056/NEJM200005043421801 . Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med. 1985;13(10):818–29. 10.1097/00003246-198510000-00009 . Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al. The Richmond Agitation–Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–44. 10.1164/rccm.2107138 . Nava S, Hill N. Non-invasive ventilation in acute respiratory failure. Lancet. 2009;374(9685):250–9. 10.1016/S0140-6736(09)60496-7 . Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;29(5):1033–56. 10.1183/09031936.00010206 . Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185–96. 10.1056/NEJMoa1503326 . MedCalc Software Ltd. Comparison of proportions calculator. Version 23.3.5. Available from: https://www.medcalc.org/calc/comparison_of_proportions.php [cited 2025 Aug 17]. National Cancer Institute. Joinpoint Regression Program. Available from: https://surveillance.cancer.gov/joinpoint/download [cited 2025 Aug 17]. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817–22. Rochwerg B, Brochard L, Elliott MW, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. 2017;50(2):1602426. 10.1183/13993003.02426-2016 . Published 2017 Aug 31. Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345–55. 10.1001/jamainternmed.2020.3539 . Esteban A, Frutos-Vivar F, Ferguson ND, Arabi Y, Apezteguía C, González M, Epstein SK, Hill NS, Nava S, Soares MA, D’Empaire G, Alía I, Anzueto A. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350(24):2452–60. 10.1056/NEJMoa032736 . Carron M, Freo U, Zorzi M, Ori C. Predictors of failure of noninvasive ventilation in patients with severe community-acquired pneumonia. J Crit Care. 2010;25(3):540. 5.4E14. .e9-540.e . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 21 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers invited by journal 13 Feb, 2026 Editor invited by journal 23 Jan, 2026 Editor assigned by journal 23 Jan, 2026 Submission checks completed at journal 21 Jan, 2026 First submitted to journal 21 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8585082","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":592961318,"identity":"b55e0d5a-8dfb-4716-a037-97a82fdacc80","order_by":0,"name":"Özlem Moçin Yazıcıoğlu","email":"","orcid":"","institution":"University of Health Sciences Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Özlem","middleName":"Moçin","lastName":"Yazıcıoğlu","suffix":""},{"id":592961319,"identity":"3be7c2ae-9558-4753-952e-3925bd4c8f8c","order_by":1,"name":"Barış Yılmaz","email":"","orcid":"","institution":"University of Health Sciences Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Barış","middleName":"","lastName":"Yılmaz","suffix":""},{"id":592961320,"identity":"a1f4d39a-35ee-4afa-8a77-8a0903754a3c","order_by":2,"name":"Gül Erdal Dönmez","email":"","orcid":"","institution":"University of Health Sciences Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gül","middleName":"Erdal","lastName":"Dönmez","suffix":""},{"id":592961321,"identity":"5cd56b15-ffd2-498e-b5be-3267ee3b9561","order_by":3,"name":"Sinem Güngör","email":"","orcid":"","institution":"University of Health Sciences Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research 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Karakurt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYFACHgaGBwcgNANDxQGw2IEHhLQkwLQcOHMAQicQreVgG0QLAz4t8jNyD35IOGOXz99zxuzzx3l35OzFDj8E2mInp9uAXQvjjLxkiYQbyZYzzvYYzzi47Zkxj3SaAVBLsrHZAexamCVyDCQSPjAbMJznMWY4uO1wYo90AkjLgcRtOLSwSeQY/0j4UG8gD9YyB6Ql/QNeLTwSOWZAhx02MAA6jOFgA0hLDn5bJHjemFkknDluYHjmWDHDmWOHjXlu5xQcSDDA7Rf59hzjGx+OVRvInUnezFBRc1iOfXb65g8fKuzkcGnBBQxIUz4KRsEoGAWjABUAAGi+ZetBwUn4AAAAAElFTkSuQmCC","orcid":"","institution":"University of Health Sciences Sureyyapasa Chest Diseases and Thoracic Surgery Teaching and Research Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zühal","middleName":"","lastName":"Karakurt","suffix":""}],"badges":[],"createdAt":"2026-01-12 20:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8585082/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8585082/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103165369,"identity":"41145e47-a7a3-4832-bcca-e26048d122b7","added_by":"auto","created_at":"2026-02-22 12:27:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":659462,"visible":true,"origin":"","legend":"\u003cp\u003eFemale ICU representation and case mix: (a) female proportion in ICU, (b) pneumonia admissions, (c) COPD admissions.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8585082/v1/9ec987270ab05e50cc15558e.png"},{"id":103165368,"identity":"437e57af-9673-48bf-b633-39ba2b17c640","added_by":"auto","created_at":"2026-02-22 12:27:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":855392,"visible":true,"origin":"","legend":"\u003cp\u003eVentilatory support trends in women: (a) IMV, (b) NIV, (c) NIV failure, (d) oxygen therapy alone.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8585082/v1/bb8670c0109b7b17ca50c0b2.png"},{"id":103165370,"identity":"d7af32bc-280e-44da-a4f9-a010d336243f","added_by":"auto","created_at":"2026-02-22 12:27:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":843229,"visible":true,"origin":"","legend":"\u003cp\u003eMortality trends: (a) overall female ICU mortality, (b) mortality among female patients, (c) overall male ICU mortality, (d) mortality among male patients.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8585082/v1/c129f441bc69e3c6bad40244.png"},{"id":103504856,"identity":"66c0c023-bab8-494e-83d4-779947b40422","added_by":"auto","created_at":"2026-02-26 13:21:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2974998,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8585082/v1/c8b57c6b-d529-447f-8db9-63511afe5556.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Time trends in mortality and ventilatory support among women with acute respiratory failure in a respiratory ICU: a 12-year retrospective cohort study”","fulltext":[{"header":"Key Findings","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eFemale representation increased after the pandemic. The proportion of women among ICU admissions declined until 2017 but reversed afterwards, showing a continuous increase and reaching 43% in 2024. Notably, this upward trend accelerated after the COVID-19 pandemic (2020–2022), suggesting that sex-specific patterns of ICU admission may have been influenced by pandemic-related case mix.\u003c/li\u003e\n \u003cli\u003eVentilatory support strategies shifted markedly during and after the pandemic.\u003cbr\u003e\u0026nbsp;Non-invasive ventilation (NIV), which dominated prior to 2018 (peak 72% in 2016), declined substantially during the pandemic years. At the same time, invasive mechanical ventilation (IMV) use increased sharply, especially after 2021, peaking at 66% in 2024. Oxygen therapy alone also rose steadily throughout the period, with its most pronounced increase occurring during and after the pandemic, reaching 42% in 2024.\u003c/li\u003e\n \u003cli\u003eCase mix changes were driven by pneumonia in the pandemic era. Pneumonia admissions in women showed a strong upward trend from 2013 onwards, but the sharpest rise occurred during and after the pandemic, when pneumonia became the predominant admission diagnosis (26% in 2024). In contrast, COPD admissions remained relatively stable or declined in recent years.\u003c/li\u003e\n \u003cli\u003eFemale mortality increased during the pandemic, while male mortality decreased afterward. Female ICU mortality, which had been declining until 2019, rose significantly from 2019 onwards, reaching 43% in 2024. Conversely, male mortality decreased after 2021, resulting in a divergence between sexes. This suggests that the pandemic had a disproportionate adverse impact on female ICU outcomes.\u003c/li\u003e\n \u003cli\u003eNIV failure patterns shifted around the pandemic. NIV failure was highest before the pandemic (25% in 2016), decreased to its lowest levels during the early pandemic period (~10–13% in 2020–2021), but then rebounded dramatically after 2022. This pattern indicates that escalation strategies for ventilatory support may have been altered during the pandemic and adjusted again in the post-pandemic period.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Introduction","content":"\u003cp\u003eSex differences in critical care outcomes have been increasingly recognized over the past two decades. Women generally have a survival advantage over men in the general population; however, this advantage is not consistently observed in the intensive care unit (ICU) setting, where disease severity, treatment strategies, and access to care may influence outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Epidemiological studies have shown that men are more frequently admitted to ICUs than women, even after adjusting for severity of illness and comorbidities, suggesting potential disparities in referral or triage practices [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In large international cohorts, the proportion of female ICU patients typically ranges from 30% to 40%, and mortality rates are variably reported as lower, similar, or higher compared to males depending on the underlying diagnosis and treatment received [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In acute respiratory failure (ARF), sex-based physiological differences\u0026mdash;including lung size, airway diameter, and respiratory muscle strength\u0026mdash;may impact ventilatory support tolerance and outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Furthermore, practice-related factors, such as underestimation of women\u0026rsquo;s height leading to higher delivered tidal volumes, have been associated with increased ventilator-induced lung injury risk in females [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite extensive research on sex differences in ICU outcomes, temporal trends in female mortality, particularly in respiratory ICUs, remain poorly characterized. Most existing studies have been cross-sectional or limited to short observation periods, providing little insight into long-term changes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Evidence regarding the impact of pandemics or large-scale viral outbreaks on sex-specific ICU mortality is scarce, and findings are inconsistent; for example, some reports suggest higher male mortality during COVID-19, while others have observed equal or higher mortality in women depending on comorbidities and care access [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The relationship between ventilatory support modality and sex-specific outcomes also remains debated. In acute respiratory distress syndrome (ARDS), studies have generally reported similar mortality between sexes, yet practice-related factors such as suboptimal protective ventilation in women could mask true differences [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, the influence of changing case mix\u0026mdash;such as pneumonia and chronic obstructive pulmonary disease (COPD) prevalence\u0026mdash;on sex-specific mortality over time has not been well studied [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven these uncertainties, we aimed to investigate sex-specific trends in ICU admissions, ventilation practices, and mortality among women with acute respiratory failure in a respiratory intensive care unit over a 12-year period. Using joinpoint regression, we sought to identify significant changes in annual percent change (APC) for overall ICU female representation, invasive and non-invasive ventilation use, and mortality before and after the COVID-19 pandemic. We hypothesized that female mortality trends would not parallel those of males, with a possible increase during the pandemic period, and that shifts in ventilation strategies and case mix\u0026mdash;particularly pneumonia and COPD prevalence\u0026mdash;might contribute to these trends. Present study allows the examination of long-term mortality trends, case mix, and ventilation practices in women admitted to a respiratory ICU over a 12-year period.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study of female patients admitted to the university respiratory intensive care unit. The ICU is a tertiary referral center specialized in respiratory failure management. The study center ICU beds number are 24 to 60 during 12 years-period. Intensive care physicians are the same physicians throughout their working hours and provide subspecialty training in intensive care at an academic center. It is the largest intensive care center in the country for respiratory diseases. A team of academic physicians works 24/7. All medical decisions are made according to pre-established protocols. All ICU protocols are organized according to international and national guidelines. The entire ICU team adheres to these rules. The study period extended from January 2013 to December 2024, covering 12 consecutive years, including the COVID-19 pandemic era.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatients\u003c/h3\u003e\n\u003cp\u003eAll adult patients (\u0026ge;\u0026thinsp;18 years) admitted to the respiratory ICU with ARF [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] were screened. Female patients were included in the analysis, while male patients were retained for comparative purposes in exploratory analyses. The exclusion criteria were ICU admissions for postoperative monitoring without ARF, readmissions within the same hospitalization, and missing key outcome data. For each patient, demographic information, comorbidities, and severity scores at admission were recorded.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eClinical data were extracted from electronic medical records and ICU databases. Variables included: demographics, age, sex, co-morbid diseases as chronic obstructive pulmonary disease (COPD) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], reason of ARF as pneumonia [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. ICU severity indices: Acute Physiology and Chronic Health Evaluation II (APACHE II) score [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Ventilatory support: use of non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), NIV and IMV together, oxygen therapy alone was recorded.\u003c/p\u003e \u003cp\u003eThe indication and application of NIV, IMV and oxygen therapy alone were well-defined according to ARF guidelines [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The sedation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], NIV [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], IMV, weaning from mechanical ventilation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], oxygen therapy-high flow nasal canula [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] application were well-defined.\u003c/p\u003e \u003cp\u003eThe study outcomes: The primary outcome was ICU mortality among women with ARF.\u003c/p\u003e \u003cp\u003eSecondary outcomes included annual trends in female representation among ICU admissions, distribution of admission diagnoses, type of ventilatory support used, NIV-IMV rates, COPD co-morbid disease annual changing, pneumonia ration annually.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized as mean (standard deviation) or median (1st and 3rd quartile), and categorical variables as counts (percentages). Between-group comparisons (female vs. male patients; survivors vs. non-survivors) were performed using Z- test [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Temporal trends in ICU female admissions, ventilatory support, and mortality were analyzed using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Joinpoint analysis identified statistically significant changes in trends over time, particularly before and after the COVID-19 pandemic. A two-sided \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were conducted using SPSS (IBM Corp., Armonk, NY, USA) and Joinpoint Regression Program (National Cancer Institute, USA) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eBaseline characteristics of female ICU patients\u003c/h2\u003e\n \u003cp\u003eBetween 2013 and 2024, a total of 17,670 patients were admitted to the respiratory ICU, of whom 5,712 (32.3%) were women. The percentage of female admissions varied over time, ranging from 31% in 2017 to a peak of 43% in 2024. The mean age of female patients remained consistently high across the study period, with a median ranging from 68 to 73 years. Age distribution did not show major annual variation, although a slight upward trend was observed after 2020. Severity of illness, as measured by the APACHE II score, was stable over time, with median values generally between 20 and 25 (1st and 3rd quartile 16\u0026ndash;30). No significant shifts in severity were observed across the pre-pandemic and pandemic periods. The percentage of women admitted with COPD as a co-morbid disease ranged from 7\u0026ndash;13% during 2013\u0026ndash;2019, stabilizing around 10\u0026ndash;12% after 2020. In contrast, pneumonia-related admissions increased substantially, from 10\u0026ndash;11% in 2013\u0026ndash;2015 to 22\u0026ndash;26% between 2018 and 2024. The highest burden of pneumonia was recorded in 2024 (26%), coinciding with the post-pandemic period (Table\u0026nbsp;1)\u003c/p\u003e\n \u003cp\u003eTable 1. Annual number of patients admitted to intensive care and age and severity scores of female patients with pneumonia and chronic obstructive pulmonary disease\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003eICU\u0026para; Beds, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0081%;\"\u003e\n \u003cp\u003ePatients, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003eFemale N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003eAPACHE II*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.9789%;\"\u003e\n \u003cp\u003eCOPD, N (%)#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003ePneumonia, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e387 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e68 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e22 (19-29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e69 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e101 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e372 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e70 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e23 (20-29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e66 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e116 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e435 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e68 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e24 (20-29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e113 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e138 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e421 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e70 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e25 (20-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e148 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e177 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e381 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e70 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e25 (20-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e138 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e192 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e450 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e69 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e22 (18-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e172 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e293 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e426 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e71(14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e22 (18-27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e175 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e235 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e566 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e69 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e20 (16-24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e190 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e356 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e684 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e69 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e20 (16-24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e236 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e452 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e2439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e896 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e73 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e21 (17-26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e252 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e578 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e666 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e73 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e23 (18-29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e160 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e382 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.2039%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.0081%;\"\u003e\n \u003cp\u003e1473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e627 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.3623%;\"\u003e\n \u003cp\u003e73 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.8164%;\"\u003e\n \u003cp\u003e25 (21-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9789%;\"\u003e\n \u003cp\u003e183 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1413%;\"\u003e\n \u003cp\u003e377 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 73.1064%;\"\u003e\n \u003cp\u003e\u0026para; ICU: intensive care unit, *APACHE II: acute physiological and chronic health evaluation II, #COPD: chronic obstructive pulmonary diseases.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003eRespiratory support in female patients\u003c/h3\u003e\n\u003cp\u003eOver the 12-year period, respiratory support strategies among women with ARF demonstrated substantial annual variation (Table\u0026nbsp;2). NIV was the predominant support modality in earlier years, reaching its highest use in 2016 (72%). During this period, women were significantly more likely than men to receive NIV (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, its utilization progressively declined, stabilizing at 44\u0026ndash;48% during 2020\u0026ndash;2024. IMV was less common among women in the early years (37\u0026ndash;49% in 2013\u0026ndash;2015) compared to men, but its use increased after the pandemic. By 2024, IMV was applied in 66% of female patients. NIV and IMV application together, the percentage of women requiring escalation from NIV to IMV ranged from 10\u0026ndash;26%, with the highest rate in 2016 (25%). After 2020, this proportion declined to approximately 10\u0026ndash;13%. The use of oxygen therapy without NIV or IMV rose significantly in the later years, from 8\u0026ndash;10% in 2014\u0026ndash;2016 to 42% in 2024. This increase was particularly evident during and after the COVID-19 pandemic (Table 2).\u003c/p\u003e\n\u003cp\u003eTable 2. \u0026nbsp; Annual numbers of female and male patients\u0026rsquo; respiratory support comparison during a 12-year period in intensive care unit.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"969\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 225px;\"\u003e\n \u003cp\u003eInvasive Mechanical Ventilation \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNon-invasive Mechanical Ventilation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 236px;\"\u003e\n \u003cp\u003eNIV and IMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 223px;\"\u003e\n \u003cp\u003eOxygen Therapy Alone \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eFemale, N (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eMale, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eFemale, N (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eMale, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eFemale, N (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eMale, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003eFemale, N (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eMale, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e143 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e334 (52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.005\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e256 (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e472 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e72 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e189 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e58 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e87 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e176 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e356 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e252 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e415 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e93 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e196 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e30 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e90 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e202 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e448 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.033\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e310 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e526 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e109 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e230 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e52 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e70 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e267 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e371 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e429 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e372 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e154 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e167 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e54 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e79 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e0.85\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e181 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e412 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e252 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e450 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e89 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e209 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e56 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e160 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e196 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e404 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.49\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e308 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e538 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e108 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e193 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e82 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e177 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e0.85\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e161 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e397 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.083\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e275 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e536 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e77 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e200 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e94 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e202 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e0.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e186 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e377 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e248 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e436 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e63 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e132 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e199 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e403 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e194 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e425 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.21\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e326 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e546 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e70 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e128 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e263 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e514 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e2439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e337 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e586 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e428 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e695 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e90 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e160 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e232 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e439 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e240 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e364 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.31\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e287 (44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e468 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e81 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e116 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e231 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e424 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003e1473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e407 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e583 (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e418 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e599 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e267 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e402 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 87px;\"\u003e\n \u003cp\u003e272 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e402 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e0.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"14\" style=\"width: 969px;\"\u003e\n \u003cp\u003eIMV: invasive mechanical ventilation, NIV: noninvasive mechanical ventilation, \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eAnnual trends (Joinpoint analysis)\u003c/h3\u003e\n\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the change in the proportion of female patients in the ICU over the years (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. a), the proportion of women admitted to the ICU with pneumonia (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. b), and the change in the presence of COPD as a comorbid disease over the years (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. c). Female representation declined between 2013\u0026ndash;2017 (APC \u0026minus;\u0026thinsp;4.7%, p\u0026thinsp;=\u0026thinsp;0.017) later years increased significantly until 2024 (APC\u0026thinsp;+\u0026thinsp;3.4%, p\u0026thinsp;=\u0026thinsp;0.003) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. a). Pneumonia admissions rose markedly 2013\u0026ndash;2018 (APC\u0026thinsp;+\u0026thinsp;15.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), continuing at a slower pace thereafter (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. b). COPD as co-morbid disease increased from 2013\u0026ndash;2018 (APC\u0026thinsp;+\u0026thinsp;16.7%, p\u0026thinsp;=\u0026thinsp;0.02) later years decreased until 2022, followed by a modest nonsignificant rebound (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. c).\u003c/p\u003e\n\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e shows the use of IMV (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. a), NIV (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. b), combined NIV and IMV (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. c), and oxygen therapy alone (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. d) in female patients with respiratory failure over the years. Ventilatory support: IMV among women increased during 2013\u0026ndash;2016 (APC\u0026thinsp;+\u0026thinsp;14.8%, p\u0026thinsp;=\u0026thinsp;0.006), declined during 2016\u0026ndash;2021 (APC \u0026minus;\u0026thinsp;13.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), then surged sharply after 2021 (APC\u0026thinsp;+\u0026thinsp;26.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. a). NIV remained stable until 2018, declined significantly between 2018\u0026ndash;2022 (APC \u0026minus;\u0026thinsp;11.1%, p\u0026thinsp;=\u0026thinsp;0.01), then rebounded after 2022 (APC\u0026thinsp;+\u0026thinsp;21.0%, p\u0026thinsp;=\u0026thinsp;0.04) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. b). NIV and IMV used initially rose, declined significantly from 2017\u0026ndash;2022 (APC \u0026minus;\u0026thinsp;21.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but escalated sharply after 2022 (APC\u0026thinsp;+\u0026thinsp;109.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. c). Oxygen therapy alone showed a continuous rise (APC\u0026thinsp;+\u0026thinsp;15.1%, p\u0026thinsp;=\u0026thinsp;0.0004), reaching 42% in 2024 (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. d).\u003c/p\u003e\n\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the change in mortality in female and male patients over the years. The changes in mortality rates female patients in the ICU over the years (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. a) and the changes in mortality rates among female patients over the years (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. b) are summarized. The changes in mortality rates male patients in the ICU over the years (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. c) and the changes in mortality rates among male patients over the years (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. d) are summarized. Female ICU mortality exhibited three phases: increase during 2013\u0026ndash;2016 (APC\u0026thinsp;+\u0026thinsp;9.8%, p\u0026thinsp;=\u0026thinsp;0.04), decrease during 2016\u0026ndash;2019 (APC \u0026minus;\u0026thinsp;12.2%, p\u0026thinsp;=\u0026thinsp;0.03), and subsequent increase during 2019\u0026ndash;2024 (APC\u0026thinsp;+\u0026thinsp;11.6%, p\u0026thinsp;=\u0026thinsp;0.01) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea\u0026ndash;b). In contrast, male ICU mortality remained stable from 2013\u0026ndash;2021 (APC\u0026thinsp;+\u0026thinsp;0.4%, NS), then declined significantly after 2021 (APC \u0026minus;\u0026thinsp;5.1%, p\u0026thinsp;=\u0026thinsp;0.04) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ec). A separate model demonstrated fluctuation in male subgroup mortality with periods of increase, decline, and renewed rise (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ed).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this 12-year cohort study of women admitted to a respiratory intensive care unit with acute respiratory failure, we identified the proportion of female admissions in 2013\u0026ndash;2017 shows decline 38% to 31% increased significantly after 2017 to 2024, reaching its highest level after the COVID-19 pandemic 43% in 2024. NIV application in female patients is predominant respiratory support in 2013 to 2019 (64%-72%), declined during the pandemic years in 2020 to 2022 (47%-48%), while IMV least 28% (2021) in pandemic pre-post pandemic (38% \u0026minus;\u0026thinsp;60% respectively) and oxygen therapy in female patients show gradually increasing in 12 years (15% to 42%). The female patients with pneumonia admissions show the rising from 10% to 26% in 12-years. COPD in female patients show the increasing 7% to 13% during the study period, in 2013 to 2018, COPD increase 16% each year, a after 2018 to 2022 shows decrease nearly 8% annually. The female ICU mortality rates are 34% to 42% in 12 years and decrease 2% APC in 2013\u0026ndash;2018, and increase after 2019 as 5.7% APC, the male mortality rates are 70%-57% and it shows, which declined after 2021 as 5% APC.\u003c/p\u003e \u003cp\u003eOur findings on female ICU representation align with previous international reports indicating that women typically comprise 30\u0026ndash;40% of ICU admissions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the observed increase in female representation after 2017 contrasts with many earlier studies that reported stable or declining female proportions over time [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This rise may partly reflect shifts in case mix, particularly the growing burden of pneumonia, which disproportionately affected women during and after the COVID-19 pandemic [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Importantly, this increase suggests that sex-specific referral and triage dynamics may have evolved in recent years, possibly influenced by pandemic-related changes in healthcare utilization and disease epidemiology.\u003c/p\u003e \u003cp\u003eThe temporal changes we observed in ventilatory support among female patients are noteworthy. NIV was the dominant strategy prior to 2018, in line with established evidence demonstrating its benefits in acute exacerbations of COPD and selected cases of hypoxemic respiratory failure [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, during the pandemic years, NIV use declined markedly, while IMV and oxygen therapy increased. This pattern mirrors global reports during COVID-19, where concerns about aerosolization risk and poor tolerance in severe hypoxemia led to earlier intubation and expanded use of high-flow oxygen therapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInterestingly, our analysis revealed that IMV utilization, once lower in female patients compared to men, rose sharply after 2021, narrowing sex-based differences in ventilatory management. Prior studies have suggested that female may be at higher risk of ventilator-induced lung injury due to underestimation of predicted body weight and inadvertent delivery of higher tidal volumes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The rise in IMV use among female patients in our cohort may therefore carry clinical implications, potentially contributing to the parallel increase in female mortality observed after the pandemic. In present study Overall, sex-based differences were more pronounced in the earlier years, with women more frequently treated with NIV and less often with IMV. These disparities diminished during and after the pandemic period, when both IMV and oxygen therapy use increased substantially among women.\u003c/p\u003e \u003cp\u003eThe divergent mortality trends between female and male in our cohort are particularly striking. While female ICU mortality decreased until 2019, it increased significantly during and after the pandemic, reaching 43% in 2024. In contrast, male mortality remained stable until 2021 and then declined. These findings suggest that the COVID-19 pandemic may have disproportionately worsened outcomes in women. Earlier studies on sex differences in ICU mortality have reported inconsistent results. Large multinational cohorts, such as the ICON audit, found no overall survival advantage for women, although regional and diagnosis-specific differences were noted [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. During the COVID-19 pandemic, several meta-analyses suggested that male sex was associated with higher mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], yet others emphasized that outcomes were strongly influenced by comorbidities, treatment accessibility, and variations in care [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Our findings add nuance to this literature by demonstrating that, in a respiratory ICU population, female mortality increased after the pandemic, even as male mortality declined. Several mechanisms may underline this pattern. First, the observed rise in IMV utilization among female after 2021 may have contributed, as IMV is consistently associated with higher mortality in patients with hypoxemic respiratory failure. Second, the increasing burden of pneumonia among female patients could have shifted the case mix toward more severe and less reversible conditions. Third, practice-related factors\u0026mdash;such as delays in escalation from NIV to IMV\u0026mdash;may have amplified sex-specific risks during the pandemic.\u003c/p\u003e \u003cp\u003eChanges in case mix also provide important context for our findings. Pneumonia became increasingly common among female admitted to the ICU, rising from approximately 10% in 2013 to over 25% in 2024. In present study the pneumonia in female patient\u0026rsquo;s annual average percent change 15.5% in 2013\u0026ndash;2018 and 4.1% in 2018 to 2024. The pandemic period did not show further increased the pneumonia proportion in female patients. This trend was particularly pronounced during and after the COVID-19 pandemic, when viral and secondary bacterial pneumonias contributed to a substantial proportion of ICU admissions worldwide [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The increased burden of pneumonia among female patients may have been a major driver of the rising mortality observed in our cohort. By contrast, COPD exacerbations, a historically common cause of ICU admission, showed relative stability or even decline in recent years. This pattern is consistent with reports of improved outpatient management, vaccination strategies, and wider use of NIV in emergency settings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The relative decline in COPD may also reflect the overshadowing impact of pneumonia and pandemic-related respiratory infections on ICU utilization. Together, these shifts suggest that the increasing predominance of pneumonia as a primary diagnosis has altered the sex-specific profile of ICU patients, disproportionately exposing female to high-mortality conditions.\u003c/p\u003e \u003cp\u003eThe dynamic patterns of NIV and IMV application observed in our study also warrant attention. NIV and IMV application rates in female patients peaked before the pandemic (25% in 2016), declined to their lowest levels during the early pandemic years (~\u0026thinsp;10\u0026ndash;13% in 2020\u0026ndash;2021), and then increased sharply again after 2022. These findings suggest evolving practices in escalation strategies and highlight potential vulnerabilities in female patients. Previous studies have emphasized that delayed transition from NIV to IMV is associated with worse outcomes, particularly in patients with pneumonia or severe hypoxemia [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The temporary decline in NIV-IMV applications during the pandemic may reflect changes in ICU practice, including earlier intubation policies and greater reliance on high-flow oxygen therapy, which reduced the proportion of patients undergoing prolonged unsuccessful NIV trials [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, the renewed increase in NIV and IMV after 2022 may indicate a reversion to pre-pandemic practices or reflect the challenges of managing an increasingly complex and older patient population.\u003c/p\u003e \u003cp\u003eImportantly, sex-specific physiological differences may contribute to these trends. Women have smaller lung volumes and reduce respiratory muscle strength compared to men, factors that may predispose them to poorer tolerance of NIV support [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In addition, potential underestimation of women\u0026rsquo;s height when setting ventilator parameters could increase the risk of patient\u0026ndash;ventilator asynchrony and ventilator-induced lung injury [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These mechanisms may partly explain why changes in ventilatory support strategies during the pandemic had disproportionate effects on female patients. In present study ventilator settings were managed by experienced team, pandemic period oxygen therapy was main respiratory support in our study.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, it was conducted in a single tertiary respiratory ICU, which may limit the generalizability of the findings to other settings with different patient populations or admission practices. Second, the retrospective design restricted our ability to assess certain key variables, such as detailed ventilator settings, timing of escalation from non-invasive to invasive ventilation, or adherence to sepsis management bundles, all of which could influence outcomes. Third, while joinpoint regression allowed us to detect significant temporal changes, the analysis cannot fully account for unmeasured confounders, such as socioeconomic factors, vaccination status, or outpatient management strategies that may have shifted over time. Fourth, the impact of the COVID-19 pandemic on ICU case mix and outcomes is complex and multifactorial; although our data captures these effects, the retrospective approach precludes causal attribution. However, certain mechanistic questions\u0026mdash;such as the role of hormonal or genetic factors in pandemic-related mortality shifts, or the precise contribution of ventilator-induced lung injury to sex-specific outcomes\u0026mdash;cannot be addressed with the available retrospective data. Similarly, we cannot directly assess quality-of-care indicators such as tidal volume accuracy, timing of escalation from non-invasive to invasive ventilation, or adherence to sepsis management bundles, which may be important mediators of observed trends. Meanwhile the study center and study team are well trained and experienced intensivist and they work 24/7 in ICU. Each unwanted event quickly and well managed. Finally, our study focused on ICU outcomes, and we were unable to provide long-term follow-up data, such as post-discharge survival or quality of life, which are particularly relevant for female patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this 12-year cohort study of women admitted to a respiratory intensive care unit with acute respiratory failure, we identified several important temporal trends. First, the proportion of female admissions increased significantly after 2017, reaching its highest level after the COVID-19 pandemic. Second, ventilatory support strategies shifted markedly: non-invasive ventilation, once the predominant modality, declined during the pandemic years, while invasive mechanical ventilation and oxygen therapy became increasingly common. Third, the case mix of female patients changed, with pneumonia admissions rising steadily and becoming the leading diagnosis in the later years. Finally, mortality trends diverged by sex: female ICU mortality increased after 2019, in contrast to male mortality, which declined after 2021.These findings suggest that evolving case mix and ventilatory practices may have disproportionately affected women, underscoring the need for heightened attention to sex- and gender-related factors in critical care. Future multicenter studies are warranted to validate these trends and to explore tailored management strategies that could mitigate excess mortality in female ICU patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eICU\u003c/b\u003e\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\"\u003e\u003cb\u003eAPACHE II\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute physiologic and chronic health evaluation\u003cb\u003es\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eARDS\u003c/b\u003e\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\"\u003e\u003cb\u003eCOPD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic obstructive pulmonary diseases\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echanges in annual percent change\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCOVID-19\u003c/b\u003e\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\"\u003e\u003cb\u003eARF\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute respiratory failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIMV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einvasive mechanical ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNIV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-invasive mechanical ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclarations\u003c/h2\u003e\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate:\u003c/h2\u003e \u003cp\u003e The study was approved by the institutional ethics committee of University of Health Sciences, Ministry of Health Sureyyapaşa Chest Diseases Thoracic Surgery Teaching and Research Hospital Ethics Committee-Istanbul-Turkiye (approval number: 2024-78 date: 24/07/2025) and conducted in accordance with the Declaration of Helsinki. The requirement for signed informed consent was waived by the institutional ethics committee due to the retrospective real life observational design. and was deemed unnecessary according to national regulations\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003e All authors agree with consent of publication. All of the material is owned by the authors and/or no permissions are required\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests:\u003c/h2\u003e \u003cp\u003eI declare that the authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eClinical trial number\u003c/h2\u003e \u003cp\u003enot applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003e \u003cb\u003eLEGENDS\u003c/b\u003e \u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eTables Legends\u003c/strong\u003e \u003cp\u003eTable\u0026nbsp;1. Annual number of patients admitted to intensive care and age and severity scores of female patients with pneumonia and chronic obstructive pulmonary disease\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2. Annual numbers of female and male patients\u0026rsquo; respiratory support comparison during a 12-year period in intensive care unit.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research did not receive funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors actively participated in the treatment of the cases at YBU, the collection of literature, the acquisition of data, the analysis, and the preparation of the article. Study design, writing manuscript: Author \u0026Ouml;YM, SG, NA, ZK, GG, BY, EAT, HBT, AB, CA, İEİ, DV, CS, FK, GED. Study analysis: ZK, SG, Data management: BY, CA, GED, HBT, AB, BY, İEİ, EAT, \u0026Ouml;YM, SG, NA, ZK, GG, Literature evaluation: FK, CS, DV, CA, BY, İEİ, HBT, AB, ZK.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to express our sincere gratitude to all intensive care nurses and healthcare assistants who have worked in intensive care in 12-year period.The following in the manuscript: \u0026lsquo;Clinical trial number: not applicable. Human Ethics and Consent to Participate declarations: The study was approved by the institutional ethics committee of University of Health Sciences, Ministry of Health Sureyyapaşa Chest Diseases Thoracic Surgery Teaching and Research Hospital Ethics Committee (approval number: 2024-78 date: 24/07/2025) and conducted in accordance with the Declaration of Helsinki. The requirement for signed informed consent was waived by the institutional ethics committee due to the retrospective real life observational design and it was deemed unnecessary according to national regulationsThis research did not receive funding.'Availability of data and materials' statement, which is present in the main manuscript, on SYSTEM as well under Data Availability sub-section of Declaration section\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGarland A. Improving the care of critically ill women. 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J Crit Care. 2010;25(3):540. 5.4E14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e.e9-540.e\u003c/span\u003e\u003cspan address=\"http://.e9-540.e\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"intensive care unit, women, sex differences, ventilatory support, pneumonia, COVID-19, mortality","lastPublishedDoi":"10.21203/rs.3.rs-8585082/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8585082/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSex-specific differences in intensive care units (ICU) outcomes are incompletely understood, particularly in respiratory ICUs. While women generally show a survival advantage in the general population, this is not consistently observed in critical care. Long-term temporal trends in women admitted to the ICU, especially during the COVID-19 pandemic, remain poorly characterized.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a retrospective cohort study of women with acute respiratory failure admitted to a tertiary respiratory ICU in T\u0026uuml;rkiye between 2013 and 2024. Demographics, comorbidities, severity score (APACHE II), admission diagnoses, and ventilatory support modalities were analyzed. The primary outcome was ICU mortality. Secondary outcomes included annual trends in female representation, ventilatory practices, and case mix. Joinpoint regression was used to calculate annual percent change (APC) and identify significant temporal shifts, including the pandemic period.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 17,670 ICU admissions, 5,712 (32.3%) were women. Female admission declined until 2017 (31%) but increased thereafter, reaching 43% in 2024 (APC\u0026thinsp;+\u0026thinsp;3.4%, p\u0026thinsp;=\u0026thinsp;0.003). Pneumonia admissions rose from 10% in 2013 to 26% in 2024, whereas COPD remained stable. Ventilatory support shifted substantially: NIV declined after 2018 (APC \u0026minus;\u0026thinsp;11.1%, p\u0026thinsp;=\u0026thinsp;0.01), IMV increased after 2021 (66% in 2024), and oxygen therapy alone rose steadily (42% in 2024). NIV and IMV application peaked in 2016 (25%), decreased during 2020\u0026ndash;2021, then increased after 2022. Female mortality decreased until 2019 but increased thereafter (APC\u0026thinsp;+\u0026thinsp;11.6%, p\u0026thinsp;=\u0026thinsp;0.01), diverging from male mortality, which declined after 2021.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFemale ICU representation and case mix changed significantly over the study period, with pneumonia and evolving ventilatory practices contributing to rising mortality after the pandemic. These findings underscore the importance of incorporating sex- and gender-specific considerations into critical care research and practice.\u003c/p\u003e","manuscriptTitle":"Time trends in mortality and ventilatory support among women with acute respiratory failure in a respiratory ICU: a 12-year retrospective cohort study”","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 12:27:44","doi":"10.21203/rs.3.rs-8585082/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-21T06:32:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164490536738432927882564224534702023329","date":"2026-02-13T23:57:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-13T13:57:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-23T08:16:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-23T07:35:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-21T19:26:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-01-21T19:21:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b3568b08-b367-41ed-8db6-577bd63b1983","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-22T12:27:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 12:27:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8585082","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8585082","identity":"rs-8585082","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}