Value of bronchial amylase level for predicting ventilator associated pneumonia in intubated adults: a systematic review and meta-analysis

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This meta-analysis aimed to explore the value of bronchial amylase for predicting VAP in intubated adults. Methods : PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2023. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Results : Overall, six studies including 769 patients were included in this review, of whom 273 (36%) were developed VAP. The cutoff values of bronchial amylase level were ranged from 8.1 U/L to 4681.5U/L. Heterogeneity between studies was assessed with an overall Q = 1.99, I 2 = 0, and P = 0.185, The pooled sensitivity and specificity for the overall population were 0.78 [95% confidence interval (CI) 0.67–0.86] and 0.75(95% CI 0.56–0.88) respectively. The DOR was 11(95% CI 3.0–40.0). The pooled AUROC was 0.83 (95%CI 0.80 - 0.86). Conclusions : The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment. Bronchial amylase Ventilator associated pneumonia Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Ventilator associated pneumonia (VAP) is the most common nosocomial infection in patients receiving mechanical ventilation that occurs 48 hours or more after tracheal intubation[ 1 ]. Aspiration of oropharyngeal and gastric content into the airway is one of the most important mechanisms for VAP, occurred in up to 88% of mechanically ventilated patients [ 2 , 3 ]. Aspiration contains macroaspiration that is usually visible clinically and microaspiration whereas cannot be witnessed or observed [ 4 ]. Microaspiration is common in ICU patients and is a diagnostic dilemma because patients at risk for aspiration who develop radiographic infiltrates may have a chemical pneumonitis rather than pneumonia [ 5 ]. α-amylase, an enzyme breaks down carbohydrates during digestion found in the salivary and pancreatic secretions, but not in the lungs or in respiratory secretions[ 6 , 7 ].α-amylase, if found in lower respiratory secretions, is can be considered to represent aspiration [ 8 , 9 ]. Its detection in low respirator secretions could be an attractive marker for predicting pneumonia. Since Weiss et al.[ 10 ] first report the elevated bronchial amylase value is associated with VAP, the bronchial amylase level has been considered as a tool to predict VAP in recent years, however, their accuracy to predict VAP is poorly characterized. In this systematic review and meta-analysis, the test characteristics of bronchial amylase level were summarized as a predictor of VAP in intubated adult patients to elucidate their diagnostic performance further and provide information for the detection of VAP patients. Method This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance [ 11 , 12 ]. We registered the study protocol at the international prospective register of systematic reviews (PROSPERO, CRD42023464200) before initiating the study. Data sources and Search strategy Relevant studies up to November 2023 were searched in the PubMed, Embase, and Cochrane Library databases with the following terms and their combinations: “amylase” and “pneumonia”, without any date or language restriction. All scanned abstracts, studies, and citations were reviewed. Moreover, references of the retrieved manuscripts were also manually cross-searched for further relevant publications. The detailed search strategies are presented in Additional file 1: Table S1 Eligibility criteria Candidate studies were screened in compliance with the following eligibility criteria: (1) studies conducted on intubated and mechanically ventilated adults;(2) studies with a clear criterion for diagnosis of VAP; (3) studies with bronchial amylase level as the index test; (4) studies published with full-text in any language; (5) studies providing sufficient data for constructing 2-by-2 tables, including true positive (TP), false positive (FP), true negative (TN), and false negative (FN). We excluded studies that met anyone of the following criteria: (1) studies that used the same population or overlapping database;(2) studies with no intubated patients or children; or (3) conference abstracts without a full text. Study selection, data extraction and quality assessment Initially, two independent reviewers (TZ and QK) checked all searched records for duplicates and performed deduplication. After that, they reviewed the title and abstract of the remaining records for relevance. Finally, the full text of candidate studies was carefully reviewed to determine their suitability for inclusion or exclusion. Any disagreement between the two reviewers was resolved through discussion with a third reviewer (HJ). The same two reviewers (TZ and QK) pre-customized an extraction form to extract the study and patient characteristics from each included study. They also recorded the diagnostic accuracy of bronchial amylase level for VAP, including the area under the receiver operating characteristic curve (AUROC), the sensitivity, the specificity, and its corresponding cutoff value. According to the diagnostic accuracy (sensitivity and specificity) and sample size in each included study, we calculated the TP, FP, TN and FN values to construct a 2×2 contingency table. The corresponding authors would be contacted to inquire about the missing data if necessary. A joint review of articles was suggested to resolve any disagreements between the two reviewers. The quality of included studies was scored independently by two reviewers (TZ and QK)using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria [ 13 ]. If existing disagreements, a discussion would be required to achieve a consensus. The quality of studies was assessed using RevMan 5.4. Statistical analysis All analyses were performed using the Stata 15.0 software (Stata Corp., College Station, TX, USA). The bivariate meta-analysis model was employed to summarize sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) [ 14 , 15 ]. The sensitivity and specificity of each included study were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). Diagnostic power was good, moderate, and poor if the AUC was more than 0.8, between 0.7 and 0.8, and less than 0.7, respectively[ 16 ]. Spearman’s correlation coefficient between the logit of sensitivity and logit of 1-specificity was calculated to determine any threshold effect; A strong positive correlation would suggest threshold effect[ 17 ]. The between-study heterogeneity was evaluated using Q test and I 2 statistics. A P value less than 0.10 for the Q test or I 2 values ≥ 50% indicated substantial heterogeneity, and then the random-effects model was applied. Confirming the stability of the present study, the sensitivity analysis and outliner exclusion were also performed. As publication bias is a concern for meta-analyses, the Deeks’ funnel plot asymmetry test was used, with P ༜0.10 indicating statistical significance[ 18 ]. Results This meta-analysis yielded 1541 primary studies through electronic database searches and 0 published study through a manual search. After deduplication and precluding irrelevant records, we carefully reviewed the full text of 11 candidate studies. Finally, six studies[ 10 , 19 – 23 ] met the eligibility criteria and were included in the quantitative analysis. Figure 1 shows the study selection process. Characteristics of the studies All included studies published in the past decade, four studies were prospective designs and two studies were retrospective designs and with a sample size ranging from 43 to 280. they were all conducted in the intensive care unit (ICU) setting. Of note, the criterion for diagnosis of VAP varied across the included studies. Table 1 shows the baseline characteristics of each included study in detail. The quality of the included studies was assessed using QUADAS-2 available in Fig. 2 . Table 1 Characteristics of the studies included in this meta-analysis First author/ Year of publication Design, setting,and country Study period Patients Cases Age (mean,years) Index test samples and device Time from intubation to samples Diagnostic criterion of VAP Observation time Weiss/2013 [ 10 ] Retrospective study; ICU; USA Aug.2008 – Jun. 2010 Mechanical ventilation patients in adult ICU 280 60 BAL; SYNCHRON activity assay Within 72 hours of intubation BAL microbial cultures of ≥ 10 4 cfu/mL and chest radiography Within 72hours after intubation Samanta/2018 [ 19 ] Prospective study; ICU; India Dec.2014 – May 2016 Clinically suspected VAP patients 151 46 Mini-BAL; Randox RX Daytona Chemistry Analyser Within 72 hours of intubation Clinically suspected VAP and mini-BAL microbial cultures of ≥ 10 4 cfu/mL Within 72hours after intubation Qu/2018 [ 21 ] Retrospective study; ICU; China May 2014 – Dec. 2016 Patients underwent tracheal intubation and mechanical ventilation 147 86.9 Tracheal aspirate; Roche automatic biochemical analyzer NA CPIS score > 6 points Within 2 weeks after intubation Rendon/2019 [ 20 ] Prospective study; ICU; Mexico Sep.2014 - Sep.2015 TBI patients intubated and mechanically ventilated 60 NA Tracheal aspirate; NA At 48 hours after intubation CDC criteria and CPIS score With the first five days of hospitalization Moussali/2022 [ 22 ] Prospective study;ICU; France Jul. 2015 - Sep.2020 OHCA patients 88 59 Mini-BAL; colorimetric enzymatic assay The first 6 hours after admission Meet clinical, radiological, and microbiologic criteria according to ESCIM and IDSA/ATS guidelines Within the first 5 days after ICU admission Mercado/2022 [ 23 ] Prospective study;ICU; Mexico Jan.2016 – Jul. 2018 Neurocritical disease patients mechanical ventilated 43 34 Tracheal aspirate; enzymatic method, Beckman Coulter 48 hours after intubation CDC criteria and CPIS score Within 30 days after intubation BAL, bronchoalveolar lavage; CPIS, clinical pulmonary infection score; OHCA, out-of-hospital cardiac arrest; NA, not available; TBI, traumatic brain injury; CDC, Centers for Disease Control; ESCIM, European Society of Intensive Care Medicine ; IDSA/ATS, Infectious Disease Society of America/American Thoracic Society Quantitative synthesis Study data and individual diagnostic estimates are summarized in Table 2 . Overall, the six included studies enrolled a total of 769 patients, of whom 273 (36%) were developed VAP. All included studies reported the cutoff value of bronchial amylase level, which ranged from 8.1 U/L to 4681.5U/L. The AUROC of individual studies ranged from 0.67 to 0.955. Heterogeneity between studies was assessed with an overall Q = 1.99, I 2 = 0, and P = 0.185, indicated no between-study heterogeneity. Spearman’s correlation coefficient was − 0.6 ( p = 0.28), indicating no threshold effect. The pooled results suggested that the bronchial amylase level exhibited moderate performance for predicting VAP with an AUROC of 0.83 [95% confidence interval (CI) 0.80–0.86] (Fig. 3 ). The summarized diagnostic accuracies indicated a pooled sensitivity of 0.78 (95% CI 0.67–0.86), a pooled specificity of 0.75 (95% CI 0.56–0.88) (Fig. 4 ), and a pooled DOR of 11(95% CI 3.0–40.0) (Fig. 5 ). The pooled positive likelihood ratio and negative likelihood ratio were 3.1 (95%CI: 1.5–6.6) and 0.29 (95%CI: 0.16–0.53), respectively. Table 2 Summary of results of the studies included in this meta-analysis First author/ Year of publication Sample size Cutoff value (U/L) Subject numbers could be calculated Sensitivity (%) Specificity (%) AUROC (95%CI) TP FP FN TN Weiss 2013[ 10 ] 280 125 50 94 21 115 70.0 55.0 0.67 (0.60–0.75) Samanta 2018[ 19 ] 151 163 72 17 26 36 73.0 68.6 0.746 (0.66–0.83) Qu 2018[ 21 ] 147 4681.5 25 24 6 92 80.1 79.3 0.813(0.721–0.896) Rendon 2019[ 20 ] 60 364 25 0 2 33 92.9 100 0.955 (0.71–0.96) Moussali 2022[ 22 ] 88 8.1 19 22 11 36 63 62 0.59 (0.464–0.717) Mercado 2022[ 23 ] 43 200 14 10 2 17 87.5 63 NA AUROC, Area under the receiver operator characteristics curve; CI, confidence interval; FN, false negative; FP, false positive; NA, not available; TN, true negative; TP, true positive; NA, not available. Sensitivity analyses Goodness-of-fit and bivariate normality analyses (Fig. 6 a and 6 b) showed that the bivariate model was robust for calculating the pooled estimates. suggesting the robustness of the present meta-analysis. Influence analysis and outlier detection (Fig. 6 c and 6 d) found outlier studies by Rendon’s study[ 20 ]. The pooled DOR ranged from 3 to 10 and the pooled AUC ranged from 0.73 to 0.80 when Rendon’s study was omitted, showing minimal change with our overall analysis. Publication bias The publication bias of the studies was assessed using the Deeks’ funnel plot asymmetry test. The slope coefficient of the six studies was associated with a P value of 0.22 (Fig. 7 ). The aforementioned results indicated symmetrical data and no significant publication bias. Discussion To the best of our knowledge, this is the first systematic review and meta-analysis to investigate the accuracy of bronchial amylase level for predicting VAP in intubated adults. The results confirmed that, overall, the bronchial amylase level performed moderately in predicting VAP in intubated adults with a pooled AUROC of 0.83 (95% CI 0.80–0.86), a pooled specificity and sensitivity of 0.75 (95% CI 0.56–0.88) and 0.78 (95% CI 0.67–0.86). This marker has advantage of inexpensive and easily measured and could be an attractive marker for predicting VAP. VAP can prolong the duration of mechanical ventilation and ICU stay, increase hospitalization costs, and possibly increase the risk of death[ 24 – 26 ].Early identification of VAP is critical because delayed treatment with antimicrobial agents has been associated with increased mortality[ 27 , 28 ]. However, the importance of using antibiotics as soon as possible must be weighed against the risks of unnecessary antibiotic use, including antibiotic resistance and superinfection[ 29 ]. Finding the right balance is challenging because VAP is difficult to diagnose, improved methods to diagnose VAP and inform the initiation of empiric antibiotics are urgently needed [ 30 , 31 ]. Microaspiration is a well-known causative factor of VAP[ 32 ]. Bronchial amylase is a reliable marker of microaspiration and is tightly linked to the development of VAP[ 8 , 10 , 19 ]. This marker has been used as surrogates in studies evaluating the efficacy of tracheal tubes[ 33 , 34 ] and subglottic secretion drainage systems[ 35 ] in preventing VAP or the development of VAP following transesophageal echocardiography[ 36 ]. Actually, as early as in the 1980s, there was some evidence[ 37 , 38 ] showing that bronchial amylase may indicate aspiration and pulmonary complication. Unfortunately, no further clinical studies have been conducted to confirm above findings until Weiss et al[ 10 ] revealed the significance of bronchoalveolar lavage amylase in diagnosing and differentiating VAP with high sensitivity and negative predictive value. After that, the bronchial amylase as a maker for predicting or diagnosing VAP has been extensively studied [ 19 – 23 , 39 ], but the results are conflicting. In the present systematic review and meta-analysis, we showed that bronchial amylase can be useful as a potential marker for early detection of VAP in clinically. The cutoff values of bronchial amylase were varied in included studies. In fact, this is the common phenomenon caused by different sampling time and methods or number of microaspiration risk factors. The extreme cutoff value of bronchial amylase was 8.1U/L in Moussali’ study[ 22 ], this could be related to the fact that the selected people were low risks of microaspiration and early sampling. In the study of Qu[ 21 ], the included patients were elderly patients and higher incidence of microaspitation. The present systematic review and meta-analysis had some limitations. First, only six studies with a relatively small sample size included this analysis, that may result in a decreased statistical power that hampered us from drawing a firm conclusion. Second, the quality assessment showed a high risk of bias in the index test. This bias might have restricted the interpretation of the true diagnostic efficacy of bronchial amylase for predicting VAP. Third, there is likely clinical heterogeneity across studies due to the largely varied patient characteristics and sampling time and methods. Forth, there is no gold standard for the diagnosis of VAP, particularly with relation to subjective indicators, such as clinical symptom and chest radiography, so observational studies are biased by the choice of gold standard. Conclusions The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment. Moreover, further studies with a larger data set and well-designed models are required to confirm the diagnostic accuracy and utility of bronchial amylase for predicting VAP. Abbreviations VAP: Ventilator associated pneumonia DOR: Diagnostic odds ratio CI: Confidence interval TP :True positive FP: False positive TN: True negative FN:False negative AUROC:Aarea under the receiver operator characteristic curve QUADAS-2:Quality Assessment of Diagnostic Accuracy Studies SROC:Summary receiver operator characteristic AUC:Area under the SROC curve ICU: Intensive care unit Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and material The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests All authors declare that they have no any conflict of interests. Funding This work was supported by Clinical Research Center of TCM Major Epidemic Diseases in Zhejiang province (NO. 2022E50009) Authors' contributions Haijun Huang and Hua Xu carried out the studies, participated in collecting data, and drafted the manuscript. Tingzhen Xu and Qinkang Shen performed the statistical analysis and participated in its design. Yuting He and Xiaozhuang Pan helped to draft the manuscript. All authors read and approved the final manuscript. Acknowledgements None. References Hunter JD: Ventilator associated pneumonia. Bmj 2012, 344:e3325. 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Bagate F, Rouzé A, Zerimech F, Boissier F, Labbe V, Razazi K, Carteaux G, de Prost N, Balduyck M, Maboudou P et al : Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study. Critical care (London, England) 2020, 24(1):679. Nandapalan V, McIlwain JC, Hamilton J: A study of alpha-amylase activity in tracheobronchial secretions of seriously ill patients with tracheostomies. The Journal of laryngology and otology 1995, 109(7):640–643. Clarke PD, Bain BC, Davies A, Levin GE, Lambert HP: Aspiration in seriously ill patients: a study of amylase in bronchial secretions. Journal of clinical pathology 1981, 34(7):803–805. Suzuki T, Saitou M, Utano Y, Utano K, Niitsuma K: Bronchoalveolar lavage (BAL) amylase and pepsin levels as potential biomarkers of aspiration pneumonia. Pulmonology 2023, 29(5):392–398. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3527420","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":245080049,"identity":"7d134275-3c8c-40e3-a3da-690e72d8e28b","order_by":0,"name":"Tingzhen Xu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tingzhen","middleName":"","lastName":"Xu","suffix":""},{"id":245080050,"identity":"74d4bf4f-b0b0-4fbc-a215-7fe3826c4d6a","order_by":1,"name":"Qinkang Shen","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qinkang","middleName":"","lastName":"Shen","suffix":""},{"id":245080051,"identity":"9d88e22a-581b-48f5-b58f-a68dcb253893","order_by":2,"name":"Yuting He","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"He","suffix":""},{"id":245080052,"identity":"17481fb0-b761-42b5-9063-6e2a4249b1d2","order_by":3,"name":"Xiaozhuang Pan","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaozhuang","middleName":"","lastName":"Pan","suffix":""},{"id":245080053,"identity":"aee08516-6b46-4a59-8166-1ca5c7d41256","order_by":4,"name":"Haijun Huang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haijun","middleName":"","lastName":"Huang","suffix":""},{"id":245080054,"identity":"c4efedfe-1ef6-4105-a4a4-75594bb6c0ad","order_by":5,"name":"Hua Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYBACAxDB2MDAwM/MfPgBaVok29nSDEjTYnCeR0GCKC3m/AfYpHl3HJY3PswD1F9jE01Qi2XDAWZj3jOHDbcd5j3wgOFYWm4DQYcdbGB8zNt2mHHbYb4EA8aGw0RoOczAcBioxX5zM4+BBHFajjGAbUncwEy0ljMMzIZz29KTZxwGBnICUX45f4BN4m2btW1//+HDDz7U2BDWAoz2Dwh2AmHlo2AUjIJRMAqIAQApdTypA92wagAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2023-10-31 17:29:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3527420/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3527420/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":46022595,"identity":"9d89eb9b-19db-473c-8ff5-2f19906b2df7","added_by":"auto","created_at":"2023-11-07 17:05:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":127658,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of identification of studies.\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/9c161893727e60ebf3ec75fd.png"},{"id":46023784,"identity":"0bf72ddc-36c2-408b-8850-92d56e65b085","added_by":"auto","created_at":"2023-11-07 17:13:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26129,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias and applicability concerns for the studies included in the meta-analysis. (a) Risk-of-bias graph; (b) Risk-of-bias summary.\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/10b7277e013a75547626313b.png"},{"id":46022596,"identity":"adde0c69-dc36-4bd0-afcc-1ad3631f42f8","added_by":"auto","created_at":"2023-11-07 17:05:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":64137,"visible":true,"origin":"","legend":"\u003cp\u003eSROC curve of bronchial amylase levelfor predicting VAP. Each circle represents individual study estimates. The diamond is the summary point representing the average sensitivity and specificity estimates. The ellipses around this summary point are the 95% confidence region (dashed line) and the 95% prediction region (dotted line).\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/5b5d0ca62ac50b3b50f17303.png"},{"id":46023786,"identity":"e34ef8a3-8bf3-49e7-a71c-1d0800cb7133","added_by":"auto","created_at":"2023-11-07 17:13:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":106185,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of the pooled sensitivity and specificity. Each solid square represents an individual study. Error bars represent 95% CI. Diamond indicates the pooled sensitivity and specificity for all of the studies.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/aaf792c735a1b66d7cefb56d.png"},{"id":46022600,"identity":"d244499a-e2d4-4901-8d54-f4caa03bd86d","added_by":"auto","created_at":"2023-11-07 17:05:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":73823,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of the pooled diagnostic odds ratio. Each solid square represents an individual study. Error bars represent 95% CI. Diamond indicates the pooled diagnostic odds ratio for all of the studies.\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/3c1b60bbd8e7b9042dc3a77a.png"},{"id":46023785,"identity":"8f486c11-0826-45ef-be2c-55e3cce3a8dd","added_by":"auto","created_at":"2023-11-07 17:13:57","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":100104,"visible":true,"origin":"","legend":"\u003cp\u003eGraphs for sensitivity analyses. a) goodness of fit; b) bivariate normality; c) influence analysis; and d) outlier detection.\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/3b1cde9cf2e2b71e7ee00ca5.png"},{"id":46022598,"identity":"9a119e99-5168-4c5f-af90-b43e1c0951fb","added_by":"auto","created_at":"2023-11-07 17:05:57","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":38240,"visible":true,"origin":"","legend":"\u003cp\u003eDeeks’ funnel plot of publication bias among studies.\u003c/p\u003e","description":"","filename":"Fig.7.png","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/a0bdc902996ce23e20ac96cc.png"},{"id":46025703,"identity":"3236d2dd-2c34-4318-af9e-73a2b7d9d8f5","added_by":"auto","created_at":"2023-11-07 17:30:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":972206,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/0a1ca470-1ece-4741-b3d4-3c5f512074ba.pdf"},{"id":46022601,"identity":"7b96c966-85ce-461f-ae42-45834f7e1950","added_by":"auto","created_at":"2023-11-07 17:05:57","extension":"docx","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":14555,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3527420/v1/e5a2523b25570970c22a0e91.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Value of bronchial amylase level for predicting ventilator associated pneumonia in intubated adults: a systematic review and meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVentilator associated pneumonia (VAP) is the most common nosocomial infection in patients receiving mechanical ventilation that occurs 48 hours or more after tracheal intubation[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Aspiration of oropharyngeal and gastric content into the airway is one of the most important mechanisms for VAP, occurred in up to 88% of mechanically ventilated patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Aspiration contains macroaspiration that is usually visible clinically and microaspiration whereas cannot be witnessed or observed [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Microaspiration is common in ICU patients and is a diagnostic dilemma because patients at risk for aspiration who develop radiographic infiltrates may have a chemical pneumonitis rather than pneumonia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eα-amylase, an enzyme breaks down carbohydrates during digestion found in the salivary and pancreatic secretions, but not in the lungs or in respiratory secretions[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].α-amylase, if found in lower respiratory secretions, is can be considered to represent aspiration [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Its detection in low respirator secretions could be an attractive marker for predicting pneumonia. Since Weiss et al.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] first report the elevated bronchial amylase value is associated with VAP, the bronchial amylase level has been considered as a tool to predict VAP in recent years, however, their accuracy to predict VAP is poorly characterized.\u003c/p\u003e \u003cp\u003eIn this systematic review and meta-analysis, the test characteristics of bronchial amylase level were summarized as a predictor of VAP in intubated adult patients to elucidate their diagnostic performance further and provide information for the detection of VAP patients.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThis meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. We registered the study protocol at the international prospective register of systematic reviews (PROSPERO, CRD42023464200) before initiating the study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData sources and Search strategy\u003c/h2\u003e \u003cp\u003eRelevant studies up to November 2023 were searched in the PubMed, Embase, and Cochrane Library databases with the following terms and their combinations: \u0026ldquo;amylase\u0026rdquo; and \u0026ldquo;pneumonia\u0026rdquo;, without any date or language restriction. All scanned abstracts, studies, and citations were reviewed. Moreover, references of the retrieved manuscripts were also manually cross-searched for further relevant publications. The detailed search strategies are presented in Additional file 1: Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria\u003c/h2\u003e \u003cp\u003eCandidate studies were screened in compliance with the following eligibility criteria: (1) studies conducted on intubated and mechanically ventilated adults;(2) studies with a clear criterion for diagnosis of VAP; (3) studies with bronchial amylase level as the index test; (4) studies published with full-text in any language; (5) studies providing sufficient data for constructing 2-by-2 tables, including true positive (TP), false positive (FP), true negative (TN), and false negative (FN). We excluded studies that met anyone of the following criteria: (1) studies that used the same population or overlapping database;(2) studies with no intubated patients or children; or (3) conference abstracts without a full text.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection, data extraction and quality assessment\u003c/h2\u003e \u003cp\u003eInitially, two independent reviewers (TZ and QK) checked all searched records for duplicates and performed deduplication. After that, they reviewed the title and abstract of the remaining records for relevance. Finally, the full text of candidate studies was carefully reviewed to determine their suitability for inclusion or exclusion. Any disagreement between the two reviewers was resolved through discussion with a third reviewer (HJ).\u003c/p\u003e \u003cp\u003eThe same two reviewers (TZ and QK) pre-customized an extraction form to extract the study and patient characteristics from each included study. They also recorded the diagnostic accuracy of bronchial amylase level for VAP, including the area under the receiver operating characteristic curve (AUROC), the sensitivity, the specificity, and its corresponding cutoff value. According to the diagnostic accuracy (sensitivity and specificity) and sample size in each included study, we calculated the TP, FP, TN and FN values to construct a 2\u0026times;2 contingency table. The corresponding authors would be contacted to inquire about the missing data if necessary. A joint review of articles was suggested to resolve any disagreements between the two reviewers.\u003c/p\u003e \u003cp\u003eThe quality of included studies was scored independently by two reviewers (TZ and QK)using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. If existing disagreements, a discussion would be required to achieve a consensus. The quality of studies was assessed using RevMan 5.4.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll analyses were performed using the Stata 15.0 software (Stata Corp., College Station, TX, USA). The bivariate meta-analysis model was employed to summarize sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The sensitivity and specificity of each included study were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). Diagnostic power was good, moderate, and poor if the AUC was more than 0.8, between 0.7 and 0.8, and less than 0.7, respectively[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Spearman\u0026rsquo;s correlation coefficient between the logit of sensitivity and logit of 1-specificity was calculated to determine any threshold effect; A strong positive correlation would suggest threshold effect[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The between-study heterogeneity was evaluated using \u003cem\u003eQ\u003c/em\u003e test and \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e statistics. A \u003cem\u003eP\u003c/em\u003e value less than 0.10 for the \u003cem\u003eQ\u003c/em\u003e test or \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e values\u0026thinsp;\u0026ge;\u0026thinsp;50% indicated substantial heterogeneity, and then the random-effects model was applied. Confirming the stability of the present study, the sensitivity analysis and outliner exclusion were also performed. As publication bias is a concern for meta-analyses, the Deeks\u0026rsquo; funnel plot asymmetry test was used, with \u003cem\u003eP\u003c/em\u003e ༜0.10 indicating statistical significance[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis meta-analysis yielded 1541 primary studies through electronic database searches and 0 published study through a manual search. After deduplication and precluding irrelevant records, we carefully reviewed the full text of 11 candidate studies. Finally, six studies[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] met the eligibility criteria and were included in the quantitative analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the study selection process.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eCharacteristics of the studies\u003c/h3\u003e\n\u003cp\u003eAll included studies published in the past decade, four studies were prospective designs and two studies were retrospective designs and with a sample size ranging from 43 to 280. they were all conducted in the intensive care unit (ICU) setting. Of note, the criterion for diagnosis of VAP varied across the included studies. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline characteristics of each included study in detail. The quality of the included studies was assessed using QUADAS-2 available in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the studies included in this meta-analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst author/\u003c/p\u003e \u003cp\u003eYear of\u003c/p\u003e \u003cp\u003epublication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDesign,\u003c/p\u003e \u003cp\u003esetting,and country\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(mean,years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIndex test samples and device\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTime from intubation to samples\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDiagnostic criterion of VAP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eObservation time\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeiss/2013\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective study; ICU; USA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAug.2008 \u0026ndash;\u003c/p\u003e \u003cp\u003eJun. 2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMechanical ventilation patients in adult ICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBAL;\u003c/p\u003e \u003cp\u003eSYNCHRON activity assay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eWithin 72 hours of intubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBAL microbial cultures of \u0026ge;\u0026thinsp;10\u003csup\u003e4\u003c/sup\u003e cfu/mL and chest radiography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWithin 72hours after intubation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSamanta/2018\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProspective study; ICU; India\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDec.2014 \u0026ndash;\u003c/p\u003e \u003cp\u003eMay 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClinically suspected VAP patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMini-BAL;\u003c/p\u003e \u003cp\u003eRandox RX Daytona Chemistry Analyser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eWithin 72 hours of intubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eClinically suspected VAP and mini-BAL microbial cultures of \u0026ge;\u0026thinsp;10\u003csup\u003e4\u003c/sup\u003e cfu/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWithin 72hours after intubation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQu/2018\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective study; ICU; China\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMay 2014 \u0026ndash;\u003c/p\u003e \u003cp\u003eDec. 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePatients underwent tracheal intubation and mechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e86.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTracheal aspirate; Roche automatic biochemical analyzer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCPIS score\u0026thinsp;\u0026gt;\u0026thinsp;6 points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWithin 2 weeks after intubation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRendon/2019\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProspective study; ICU; Mexico\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSep.2014 - Sep.2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTBI patients intubated and mechanically ventilated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTracheal aspirate;\u003c/p\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAt 48 hours after intubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCDC criteria and CPIS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWith the first five days of hospitalization\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMoussali/2022\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProspective study;ICU; France\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJul. 2015 - Sep.2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOHCA patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMini-BAL;\u003c/p\u003e \u003cp\u003ecolorimetric enzymatic assay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eThe first 6 hours after admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMeet clinical, radiological, and microbiologic criteria according to ESCIM and IDSA/ATS guidelines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWithin the first 5\u003c/p\u003e \u003cp\u003edays after\u003c/p\u003e \u003cp\u003eICU admission\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMercado/2022\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProspective study;ICU; Mexico\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJan.2016 \u0026ndash; Jul. 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeurocritical disease patients mechanical ventilated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTracheal aspirate; enzymatic method, Beckman Coulter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e48 hours after intubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCDC criteria and CPIS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWithin 30 days\u003c/p\u003e \u003cp\u003eafter intubation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eBAL, bronchoalveolar lavage; CPIS, clinical pulmonary infection score; OHCA, out-of-hospital cardiac arrest; NA, not available; TBI, traumatic brain injury; CDC, Centers for Disease Control; ESCIM, European Society of Intensive Care Medicine ; IDSA/ATS, Infectious Disease Society of America/American Thoracic Society\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eQuantitative synthesis\u003c/h2\u003e \u003cp\u003eStudy data and individual diagnostic estimates are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Overall, the six included studies enrolled a total of 769 patients, of whom 273 (36%) were developed VAP. All included studies reported the cutoff value of bronchial amylase level, which ranged from 8.1 U/L to 4681.5U/L. The AUROC of individual studies ranged from 0.67 to 0.955. Heterogeneity between studies was assessed with an overall \u003cem\u003eQ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.99, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.185, indicated no between-study heterogeneity. Spearman\u0026rsquo;s correlation coefficient was \u0026minus;\u0026thinsp;0.6 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.28), indicating no threshold effect. The pooled results suggested that the bronchial amylase level exhibited moderate performance for predicting VAP with an AUROC of 0.83 [95% confidence interval (CI) 0.80\u0026ndash;0.86] (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The summarized diagnostic accuracies indicated a pooled sensitivity of 0.78 (95% CI 0.67\u0026ndash;0.86), a pooled specificity of 0.75 (95% CI 0.56\u0026ndash;0.88) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), and a pooled DOR of 11(95% CI 3.0\u0026ndash;40.0) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The pooled positive likelihood ratio and negative likelihood ratio were 3.1 (95%CI: 1.5\u0026ndash;6.6) and 0.29 (95%CI: 0.16\u0026ndash;0.53), respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of results of the studies included in this meta-analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFirst author/\u003c/p\u003e \u003cp\u003eYear of\u003c/p\u003e \u003cp\u003epublication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSample\u003c/p\u003e \u003cp\u003esize\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCutoff value\u003c/p\u003e \u003cp\u003e(U/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e \u003cp\u003eSubject numbers could be calculated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSensitivity (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSpecificity (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAUROC (95%CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeiss 2013[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e55.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.67 (0.60\u0026ndash;0.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSamanta 2018[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e73.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e68.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.746 (0.66\u0026ndash;0.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQu 2018[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4681.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e80.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e79.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.813(0.721\u0026ndash;0.896)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRendon 2019[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e92.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.955 (0.71\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMoussali 2022[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.59 (0.464\u0026ndash;0.717)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMercado 2022[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e87.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eAUROC, Area under the receiver operator characteristics curve; CI, confidence interval; FN, false negative; FP, false positive; NA, not available; TN, true negative; TP, true positive; NA, not available.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analyses\u003c/h2\u003e \u003cp\u003eGoodness-of-fit and bivariate normality analyses (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ea and \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eb) showed that the bivariate model was robust for calculating the pooled estimates. suggesting the robustness of the present meta-analysis. Influence analysis and outlier detection (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ec and \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ed) found outlier studies by Rendon\u0026rsquo;s study[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The pooled DOR ranged from 3 to 10 and the pooled AUC ranged from 0.73 to 0.80 when Rendon\u0026rsquo;s study was omitted, showing minimal change with our overall analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePublication bias\u003c/h2\u003e \u003cp\u003eThe publication bias of the studies was assessed using the Deeks\u0026rsquo; funnel plot asymmetry test. The slope coefficient of the six studies was associated with a \u003cem\u003eP\u003c/em\u003e value of 0.22 (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). The aforementioned results indicated symmetrical data and no significant publication bias.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first systematic review and meta-analysis to investigate the accuracy of bronchial amylase level for predicting VAP in intubated adults. The results confirmed that, overall, the bronchial amylase level performed moderately in predicting VAP in intubated adults with a pooled AUROC of 0.83 (95% CI 0.80\u0026ndash;0.86), a pooled specificity and sensitivity of 0.75 (95% CI 0.56\u0026ndash;0.88) and 0.78 (95% CI 0.67\u0026ndash;0.86). This marker has advantage of inexpensive and easily measured and could be an attractive marker for predicting VAP.\u003c/p\u003e \u003cp\u003eVAP can prolong the duration of mechanical ventilation and ICU stay, increase hospitalization costs, and possibly increase the risk of death[\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].Early identification of VAP is critical because delayed treatment with antimicrobial agents has been associated with increased mortality[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, the importance of using antibiotics as soon as possible must be weighed against the risks of unnecessary antibiotic use, including antibiotic resistance and superinfection[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Finding the right balance is challenging because VAP is difficult to diagnose, improved methods to diagnose VAP and inform the initiation of empiric antibiotics are urgently needed [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMicroaspiration is a well-known causative factor of VAP[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Bronchial amylase is a reliable marker of microaspiration and is tightly linked to the development of VAP[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This marker has been used as surrogates in studies evaluating the efficacy of tracheal tubes[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] and subglottic secretion drainage systems[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] in preventing VAP or the development of VAP following transesophageal echocardiography[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Actually, as early as in the 1980s, there was some evidence[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] showing that bronchial amylase may indicate aspiration and pulmonary complication. Unfortunately, no further clinical studies have been conducted to confirm above findings until Weiss et al[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] revealed the significance of bronchoalveolar lavage amylase in diagnosing and differentiating VAP with high sensitivity and negative predictive value. After that, the bronchial amylase as a maker for predicting or diagnosing VAP has been extensively studied [\u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], but the results are conflicting. In the present systematic review and meta-analysis, we showed that bronchial amylase can be useful as a potential marker for early detection of VAP in clinically.\u003c/p\u003e \u003cp\u003eThe cutoff values of bronchial amylase were varied in included studies. In fact, this is the common phenomenon caused by different sampling time and methods or number of microaspiration risk factors. The extreme cutoff value of bronchial amylase was 8.1U/L in Moussali\u0026rsquo; study[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], this could be related to the fact that the selected people were low risks of microaspiration and early sampling. In the study of Qu[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the included patients were elderly patients and higher incidence of microaspitation.\u003c/p\u003e \u003cp\u003eThe present systematic review and meta-analysis had some limitations. First, only six studies with a relatively small sample size included this analysis, that may result in a decreased statistical power that hampered us from drawing a firm conclusion. Second, the quality assessment showed a high risk of bias in the index test. This bias might have restricted the interpretation of the true diagnostic efficacy of bronchial amylase for predicting VAP. Third, there is likely clinical heterogeneity across studies due to the largely varied patient characteristics and sampling time and methods. Forth, there is no gold standard for the diagnosis of VAP, particularly with relation to subjective indicators, such as clinical symptom and chest radiography, so observational studies are biased by the choice of gold standard.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment. Moreover, further studies with a larger data set and well-designed models are required to confirm the diagnostic accuracy and utility of bronchial amylase for predicting VAP.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVAP:\u0026nbsp;Ventilator associated pneumonia\u003c/p\u003e\n\u003cp\u003eDOR: Diagnostic odds ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTP :True positive \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFP: False positive \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTN: True negative\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFN:False negative\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAUROC:Aarea under the receiver operator characteristic curve\u003c/p\u003e\n\u003cp\u003eQUADAS-2:Quality Assessment of Diagnostic Accuracy Studies\u003c/p\u003e\n\u003cp\u003eSROC:Summary receiver operator characteristic\u003c/p\u003e\n\u003cp\u003eAUC:Area under the SROC curve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICU: Intensive care unit\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no any conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Clinical Research Center of TCM Major Epidemic Diseases in Zhejiang province (NO.\u0026nbsp;2022E50009)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHaijun Huang and\u0026nbsp;Hua Xu\u0026nbsp;carried out the studies, participated in collecting data, and drafted the manuscript.\u0026nbsp;Tingzhen Xu\u0026nbsp;and\u0026nbsp;Qinkang Shen\u0026nbsp;performed the statistical analysis and participated in its design.\u0026nbsp;Yuting He and Xiaozhuang Pan\u0026nbsp;helped to draft the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHunter JD: Ventilator associated pneumonia. Bmj 2012, 344:e3325.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCook D, De Jonghe B, Brochard L, Brun-Buisson C: Influence of airway management on ventilator-associated pneumonia: evidence from randomized trials. Jama 1998, 279(10):781\u0026ndash;787.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetheny NA, Clouse RE, Chang YH, Stewart BJ, Oliver DA, Kollef MH: Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Critical care medicine 2006, 34(4):1007\u0026ndash;1015.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMandell LA, Niederman MS: Aspiration Pneumonia. 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The clinical respiratory journal 2018, 12(4):1685\u0026ndash;1692.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoussali A, Cauchois E, Carvelli J, Hraeich S, Bouzana F, Lesaux A, Boucekine M, Bichon A, Gainnier M, Fromonot J \u003cem\u003eet al\u003c/em\u003e: Salivary Alpha Amylase Bronchial Measure for Early Aspiration Pneumonia Diagnosis in Patients Treated With Therapeutic Hypothermia After Out-of-hospital Cardiac Arrest. Frontiers in medicine 2022, 9:880803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMercado-Longoria R, Galindo-Galindo JO, Ataxca-Gonzalez MA, Colunga-Pedraza PR, Pe\u0026ntilde;a-Lozano SP, Llaca-D\u0026iacute;az JM, Rend\u0026oacute;n-Ram\u0026iacute;rez EJ: Thoracic ultrasound alone or in combination with tracheal amylase as a tool predictor of ventilator-associated pneumonia in neurocritical patients. Medicine 2022, 101(48):e32149.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelsen WG, Rovers MM, Groenwold RH, Bergmans DC, Camus C, Bauer TT, Hanisch EW, Klarin B, Koeman M, Krueger WA \u003cem\u003eet al\u003c/em\u003e: Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. The Lancet Infectious diseases 2013, 13(8):665\u0026ndash;671.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH: Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 2008, 134(2):281\u0026ndash;287.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalanuria AA, Ziai W, Mirski M: Ventilator-associated pneumonia in the ICU. Critical care (London, England) 2014, 18(2):208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvarez-Lerma F: Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive care medicine 1996, 22(5):387\u0026ndash;394.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuti EL, Patel AA, Coleman CI: Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis. Journal of critical care 2008, 23(1):91\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuyt CE, Br\u0026eacute;chot N, Trouillet JL, Chastre J: Antibiotic stewardship in the intensive care unit. Critical care (London, England) 2014, 18(5):480.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFernando SM, Tran A, Cheng W, Klompas M, Kyeremanteng K, Mehta S, English SW, Muscedere J, Cook DJ, Torres A \u003cem\u003eet al\u003c/em\u003e: Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive care medicine 2020, 46(6):1170\u0026ndash;1179.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapazian L, Klompas M, Luyt CE: Ventilator-associated pneumonia in adults: a narrative review. Intensive care medicine 2020, 46(5):888\u0026ndash;906.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValencia M, Torres A: Ventilator-associated pneumonia. Current opinion in critical care 2009, 15(1):30\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaillette E, Girault C, Brunin G, Zerimech F, Behal H, Chiche A, Broucqsault-Dedrie C, Fayolle C, Minacori F, Alves I \u003cem\u003eet al\u003c/em\u003e: Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial. Intensive care medicine 2017, 43(11):1562\u0026ndash;1571.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonsel A, Lu Q, Le Corre M, Brisson H, Arbelot C, Vezinet C, Fl\u0026eacute;ron MH, Ibanez-Est\u0026egrave;ve C, Zerimech F, Balduyck M \u003cem\u003eet al\u003c/em\u003e: Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial. Anesthesiology 2016, 124(5):1041\u0026ndash;1052.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMillot G, Boddaert P, Parmentier-Decrucq E, Palud A, Balduyck M, Maboudou P, Zerimech F, Wallet F, Preau S, Nseir S: Impact of subglottic secretion drainage on microaspiration in critically ill patients: a prospective observational study. Annals of translational medicine 2018, 6(21):416.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagate F, Rouz\u0026eacute; A, Zerimech F, Boissier F, Labbe V, Razazi K, Carteaux G, de Prost N, Balduyck M, Maboudou P \u003cem\u003eet al\u003c/em\u003e: Transesophageal echocardiography-associated tracheal microaspiration and ventilator-associated pneumonia in intubated critically ill patients: a multicenter prospective observational study. Critical care (London, England) 2020, 24(1):679.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNandapalan V, McIlwain JC, Hamilton J: A study of alpha-amylase activity in tracheobronchial secretions of seriously ill patients with tracheostomies. The Journal of laryngology and otology 1995, 109(7):640\u0026ndash;643.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClarke PD, Bain BC, Davies A, Levin GE, Lambert HP: Aspiration in seriously ill patients: a study of amylase in bronchial secretions. Journal of clinical pathology 1981, 34(7):803\u0026ndash;805.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuzuki T, Saitou M, Utano Y, Utano K, Niitsuma K: Bronchoalveolar lavage (BAL) amylase and pepsin levels as potential biomarkers of aspiration pneumonia. Pulmonology 2023, 29(5):392\u0026ndash;398.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bronchial amylase, Ventilator associated pneumonia, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-3527420/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3527420/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: The ability of bronchial amylase level for predicting ventilator associated pneumonia (VAP) has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of bronchial amylase for predicting VAP in intubated adults.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2023. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Overall, six studies including 769 patients were included in this review, of whom 273 (36%) were developed VAP. The cutoff values of bronchial amylase level were ranged from 8.1 U/L to 4681.5U/L. Heterogeneity between studies was assessed with an overall \u003cem\u003eQ\u003c/em\u003e = 1.99, \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e = 0, and \u003cem\u003eP\u003c/em\u003e = 0.185, The pooled sensitivity and specificity for the overall population were 0.78 [95% confidence interval (CI) 0.67–0.86] and 0.75(95% CI 0.56–0.88) respectively. The DOR was 11(95% CI 3.0–40.0). The pooled AUROC was 0.83 (95%CI 0.80 - 0.86).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment.\u003c/p\u003e","manuscriptTitle":"Value of bronchial amylase level for predicting ventilator associated pneumonia in intubated adults: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-07 17:05:52","doi":"10.21203/rs.3.rs-3527420/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5e466c54-7d92-423a-b1ac-3c4d0b8163cc","owner":[],"postedDate":"November 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-11-14T12:59:20+00:00","versionOfRecord":[],"versionCreatedAt":"2023-11-07 17:05:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3527420","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3527420","identity":"rs-3527420","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}