A high α1-antitrypsin/interleukin-10 ratio predicts bacterial pneumonia in adults with community-acquired pneumonia: a prospective cohort study.

Bacterial pneumonia Biomarker Community-acquired pneumonia Interleukin-10 α1-antitrypsin

Journal

Pneumonia (Nathan Qld.)
ISSN: 2200-6133
Titre abrégé: Pneumonia (Nathan)
Pays: England
ID NLM: 101663459

Informations de publication

Date de publication:
25 Oct 2023
Historique:
received: 11 07 2023
accepted: 10 10 2023
medline: 25 10 2023
pubmed: 25 10 2023
entrez: 25 10 2023
Statut: epublish

Résumé

Current microbiological tests fail to identify the causative microorganism in more than half of all pneumonia cases. We explored biomarkers that could be used for differentiating between bacterial and viral pneumonia in patients with community-acquired pneumonia (CAP). In this prospective cohort study conducted in Japan, data obtained from adult patients with bacterial pneumonia, including bacterial and viral coinfections (bacterial pneumonia [BP] group), and purely viral pneumonia (VP group) at diagnosis were analyzed using multivariate logistic regression analysis to identify predictors of bacterial pneumonia. Furthermore, a decision tree was developed using the predictors. A total of 210 patients were analyzed. The BP and VP groups comprised 108 and 18 patients, respectively. The other 84 patients had no identified causative microorganism. The two groups shared similar characteristics, including disease severity; however, a significant difference (p < 0.05) was observed between the two groups regarding sputum type; sputum volume score; neutrophil counts; and serum levels of interleukin (IL)-8, IL-10, and α1-antitrypsin (AAT). Sputum volume score (p < 0.001), IL-10 (p < 0.001), and AAT (p = 0.008) were ultimately identified as predictors of BP. The area under the curve for these three variables on the receiver operating characteristic (ROC) curve was 0.927 (95% confidence interval [CI]: 0.881-0.974). The ROC curve for sputum volume score and an AAT/IL-10 ratio showed a diagnostic cutoff of 1 + and 65, respectively. Logistic regression analysis using dichotomized variables at the cutoff values showed that the odds ratios for the diagnosis of BP were 10.4 (95% CI: 2.2-50.2) for sputum volume score (absence vs. presence) and 19.8 (95% CI: 4.7-83.2) for AAT/IL-10 ratio (< 65 vs. ≥ 65). Considering that obtaining a definitive etiologic diagnosis with the current testing methods is difficult and time consuming, a decision tree with two predictors, namely sputum volume and the AAT/IL-10 ratio, can be useful in predicting BP among patients diagnosed with CAP and facilitating the appropriate use of antibiotics. UMIN000034673 registered on November 29, 2018.

Sections du résumé

BACKGROUND BACKGROUND
Current microbiological tests fail to identify the causative microorganism in more than half of all pneumonia cases. We explored biomarkers that could be used for differentiating between bacterial and viral pneumonia in patients with community-acquired pneumonia (CAP).
METHODS METHODS
In this prospective cohort study conducted in Japan, data obtained from adult patients with bacterial pneumonia, including bacterial and viral coinfections (bacterial pneumonia [BP] group), and purely viral pneumonia (VP group) at diagnosis were analyzed using multivariate logistic regression analysis to identify predictors of bacterial pneumonia. Furthermore, a decision tree was developed using the predictors.
RESULTS RESULTS
A total of 210 patients were analyzed. The BP and VP groups comprised 108 and 18 patients, respectively. The other 84 patients had no identified causative microorganism. The two groups shared similar characteristics, including disease severity; however, a significant difference (p < 0.05) was observed between the two groups regarding sputum type; sputum volume score; neutrophil counts; and serum levels of interleukin (IL)-8, IL-10, and α1-antitrypsin (AAT). Sputum volume score (p < 0.001), IL-10 (p < 0.001), and AAT (p = 0.008) were ultimately identified as predictors of BP. The area under the curve for these three variables on the receiver operating characteristic (ROC) curve was 0.927 (95% confidence interval [CI]: 0.881-0.974). The ROC curve for sputum volume score and an AAT/IL-10 ratio showed a diagnostic cutoff of 1 + and 65, respectively. Logistic regression analysis using dichotomized variables at the cutoff values showed that the odds ratios for the diagnosis of BP were 10.4 (95% CI: 2.2-50.2) for sputum volume score (absence vs. presence) and 19.8 (95% CI: 4.7-83.2) for AAT/IL-10 ratio (< 65 vs. ≥ 65).
CONCLUSIONS CONCLUSIONS
Considering that obtaining a definitive etiologic diagnosis with the current testing methods is difficult and time consuming, a decision tree with two predictors, namely sputum volume and the AAT/IL-10 ratio, can be useful in predicting BP among patients diagnosed with CAP and facilitating the appropriate use of antibiotics.
TRIAL REGISTRATION BACKGROUND
UMIN000034673 registered on November 29, 2018.

Identifiants

pubmed: 37876022
doi: 10.1186/s41479-023-00118-4
pii: 10.1186/s41479-023-00118-4
pmc: PMC10599029
doi:

Types de publication

Journal Article

Langues

eng

Pagination

16

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

Références

Aliberti S, Dela Cruz CS, Amati F, Sotgiu G, Restrepo MI. Community-acquired pneumonia. Lancet. 2021;398:906–19.
pubmed: 34481570
Gadsby NJ, Musher DM. The microbial etiology of community-acquired pneumonia in adults: from classical bacteriology to host transcriptional signatures. Clin Microbiol Rev. 2022;35:e0001522.
pubmed: 36165783
Torres A, Cilloniz C, Niederman MS, Menéndez R, Chalmers JD, Wunderink RG, et al. Pneumonia Nat Rev Dis Primers. 2021;7:25.
pubmed: 33833230
Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18:95–107.
pubmed: 29037960
Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10:CD007498.
pubmed: 29025194
Huang DT, Yealy DM, Filbin MR, Brown AM, Chang CH, Doi Y, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018;379:236–49.
pubmed: 29781385 pmcid: 6197800
Malinverni S, Nuñez M, Cotton F, Martiny D, Collot V, Konopnicki D, et al. Is procalcitonin a reliable marker of bacterial community-acquired pneumonia in adults admitted to the emergency department during SARS-CoV-2 pandemic? Eur J Emerg Med. 2021;28:312–4.
pubmed: 34187994
Carbonell R, Urgelés S, Salgado M, Rodríguez A, Reyes LF, Fuentes YV, et al. Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients. J Infect. 2022;85:374–81.
pubmed: 35781017 pmcid: 9245395
Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200:e45–67.
pubmed: 31573350 pmcid: 6812437
Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. Adults. N Engl J Med. 2015;373:415–27.
pubmed: 26172429 pmcid: 4728150
Carugati M, Aliberti S, Reyes LF, Franco Sadud R, Irfan M, Prat C, et al. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study. ERJ Open Res. 2018;4:00096–2018.
pubmed: 30474036 pmcid: 6174282
Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020;12:11.
pubmed: 33024653
Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Köhnlein T, Welte T. The discovery of α1-antitrypsin and its role in health and disease. Respir Med. 2011;105:1129–39.
Venembre P, Boutten A, Seta N, Dehoux MS, Crestani B, Aubier M, et al. Secretion of alpha 1-antitrypsin by alveolar epithelial cells. FEBS Lett. 1994;346:171–4.
Belchamber KBR, Walker EM, Stockley RA, Sapey E. Monocytes and macrophages in alpha-1 antitrypsin deficiency. Int J Chron Obstruct Pulmon Dis. 2020;15:3183–92.
pubmed: 33311976 pmcid: 7725100
Ehlers MR. Immune-modulating effects of alpha-1 antitrypsin. Biol Chem. 2014;395:1187–93.
pubmed: 24854541 pmcid: 4237306
Valim C, Ahmad R, Lanaspa M, Tan Y, Acácio S, Gillette MA, et al. Responses to bacteria, virus, and malaria distinguish the etiology of pediatric clinical pneumonia. Am J Respir Crit Care Med. 2016;193:448–59.
pubmed: 26469764 pmcid: 5440057
Porte R, Davoudian S, Asgari F, Parente R, Mantovani A, Garlanda C, Bottazzi B. The Long Pentraxin PTX3 as a humoral innate immunity functional player and biomarker of infections and sepsis. Front Immunol. 2019;10:794.
pubmed: 31031772 pmcid: 6473065
Saito A, Aoki N, Odagiri S, Niki Y, Yamaguchi K, Utada N, et al. Respiratory tract committee, protocol composition committee, clinical trial committee, Japanese society of chemotherapy. Committee Report: Clinical trial protocol for a new antimicrobial agent for the treatment of respiratory tract infections. J Infect Chemother. 2002;8:273–319.
pubmed: 12373495
Musher DM, Abers MS, Bartlett JG. Evolving understanding of the causes of pneumonia in adults, with special attention to the role of pneumococcus. Clin Infect Dis. 2017;65:1736–44.
pubmed: 29028977
Alimi Y, Lim WS, Lansbury L, Leonardi-Bee J, Nguyen-Van-Tam JS. Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe. J Clin Virol. 2017;95:26–35.
pubmed: 28837859 pmcid: 7185624
Altiner A, Wilm S, Däubener W, Bormann C, Pentzek M, Abholz HH, et al. Sputum colour for diagnosis of a bacterial infection in patients with acute cough. Scand J Prim Health Care. 2009;27:70–3.
pubmed: 19242860 pmcid: 3410464
Huijskens EGW, Koopmans M, Palmen FMH, van Erkel AJM, Mulder PGH, Rossen JWA. The value of signs and symptoms in differentiating between bacterial, viral and mixed aetiology in patients with community-acquired pneumonia. J Med Microbiol. 2014;63:441–52.
pubmed: 24344207
Haran JP, Buglione-Corbett R, Lu S. Cytokine markers as predictors of type of respiratory infection in patients during the influenza season. Am J Emerg Med. 2013;31:816–21.
pubmed: 23481156
Lu L, Zhang H, Dauphars DJ, He YW. A potential role of interleukin 10 in COVID-19 pathogenesis. Trends Immunol. 2021;42:3–5.
pubmed: 33214057
Hedlund J. Community-acquired pneumonia requiring hospitalization. Factors of importance for the short-and long term prognosis. Scand J Infect Dis Suppl. 1995;97:1–60.
pubmed: 8584866
Pertzov B, Shapira G, Abushkara S, Cohen S, Turjeman A, Kramer MR, et al. Lower serum alpha 1 antitrypsin levels in patients with severe COVID-19 compared with patients hospitalized due to non-COVID-19 pneumonia. Infect Dis (Lond). 2022;54:846–51.
pubmed: 35975662
National Institute for Health and Care Excellence. Pneumonia in adults: diagnosis and management (CG191). NICE, 2014 (Last Update: Jul 7, 2022).
National Institute for Health and Care Excellence. Pneumonia (community-acquired): antimicrobial prescribing (NG138). NICE, 2019.
Cals JW, Ebell MH. C-reactive protein: guiding antibiotic prescribing decisions at the point of care. Br J Gen Pract. 2018;68:112–3.
pubmed: 29472204 pmcid: 5819954
Christ-Crain M, Stolz D, Bingisser R, Müller C, Miedinger D, Huber PR, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174:84–93.
pubmed: 16603606
Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014;371:1619–28.
pubmed: 25337751
Self WH, Balk RA, Grijalva CG, Williams DJ, Zhu Y, Anderson EJ, et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis. 2017;65:183–90.
pubmed: 28407054
Kamat IS, Ramachandran V, Eswaran H, Abers MS, Musher DM. Low procalcitonin, community acquired pneumonia, and antibiotic therapy. Lancet Infect Dis. 2018;18:496–7.
pubmed: 29695359
Kamat IS, Ramachandran V, Eswaran H, Guffey D, Musher DM. Procalcitonin to distinguish viral from bacterial pneumonia: a systematic review and meta-analysis. Clin Infect Dis. 2020;70:538–42.
pubmed: 31241140
Pletz MW, Blasi F, Chalmers JD, Dela Cruz CS, Feldman C, Luna CM, et al. International Perspective on the New 2019 American Thoracic Society/Infectious Diseases Society of America Community-Acquired Pneumonia Guideline: a critical appraisal by a global expert panel. Chest. 2020;158:1912–8.
pubmed: 32858009
Yunus I, Fasih A, Wang Y. The use of procalcitonin in the determination of severity of sepsis, patient outcomes and infection characteristics. PLoS ONE. 2018;13:e0206527.
pubmed: 30427887 pmcid: 6235293
Tjendra Y, Al Mana AF, Espejo AP, Akgun Y, Millan NC, Gomez-Fernandez C, et al. Predicting disease severity and outcome in COVID-19 patients: a review of multiple biomarkers. Arch Pathol Lab Med. 2020;144:1465–74.
pubmed: 32818235
Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370.
pmcid: 7194648
Kyriazopoulou E, Leventogiannis K, Tavoulareas G, Mainas E, Toutouzas K, Mathas C, et al. Presepsin as a diagnostic and prognostic biomarker of severe bacterial infections and COVID-19. Sci Rep. 2023;13:3814.
pubmed: 36882572 pmcid: 9990570
Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165:710–8.
pubmed: 17182981
Ruggiero P, McMillen T, Tang YW, Babady NE. Evaluation of the BioFire FilmArray respiratory panel and the GenMark eSensor respiratory viral panel on lower respiratory tract specimens. J Clin Microbiol. 2014;52:288–90.
pubmed: 24131685 pmcid: 3911424
Berastegui-Cabrera J, Aguilar-Guisado M, Crespo-Rivas JC, López-Verdugo M, Merino L, Escoresca-Ortega A, et al. Prepandemic viral community-acquired pneumonia: Diagnostic sensitivity and specificity of nasopharyngeal swabs and performance of clinical severity scores. J Med Virol. 2023;95:e28317.
pubmed: 36396153
Locher K, Roscoe D, Jassem A, Wong T, Hoang LMN, Charles M, et al. FilmArray respiratory panel assay: an effective method for detecting viral and atypical bacterial pathogens in bronchoscopy specimens. Diagn Microbiol Infect Dis. 2019;95:114880.
pubmed: 31607515 pmcid: 7132745

Auteurs

Taiga Miyazaki (T)

Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. taiga_miyazaki@med.miyazaki-u.ac.jp.
Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan. taiga_miyazaki@med.miyazaki-u.ac.jp.

Kiyoyasu Fukushima (K)

Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Isahaya, Japan.

Kohji Hashiguchi (K)

Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.

Shotaro Ide (S)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
Isahaya General Hospital, Isahaya, Japan.

Tsutomu Kobayashi (T)

Sasebo Chuo Hospital, Sasebo, Japan.

Toyomitsu Sawai (T)

Nagasaki Harbor Medical Center, Nagasaki, Japan.

Kazuhiro Yatera (K)

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.

Yoshihisa Kohno (Y)

Kouseikai Hospital, Nagasaki, Japan.

Yuichi Fukuda (Y)

Sasebo City General Hospital, Sasebo, Japan.

Yoji Futsuki (Y)

Saiseikai Nagasaki Hospital, Nagasaki, Japan.

Yuichi Matsubara (Y)

Juko Memorial Nagasaki Hospital, Nagasaki, Japan.

Hironobu Koga (H)

Aino Memorial Hospital, Unzen, Japan.

Tomo Mihara (T)

Nagasaki Medical Center, Omura, Japan.

Eisuke Sasaki (E)

Ureshino Medical Center, Ureshino, Japan.

Nobuyuki Ashizawa (N)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.

Tatsuro Hirayama (T)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.

Takahiro Takazono (T)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.

Kazuko Yamamoto (K)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine, Okinawa, Japan.

Yoshifumi Imamura (Y)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
Medical Education Development Center, Nagasaki University Hospital, Nagasaki, Japan.

Norihito Kaku (N)

Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Kosuke Kosai (K)

Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Yoshitomo Morinaga (Y)

Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

Katsunori Yanagihara (K)

Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Hiroshi Mukae (H)

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.

Classifications MeSH