{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:42:31Z","timestamp":1790484151130,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T00:00:00Z","timestamp":1559520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.<\/jats:p>","DOI":"10.3390\/jcm8060786","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T11:31:01Z","timestamp":1559561461000},"page":"786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients"],"prefix":"10.3390","volume":"8","author":[{"given":"Guillaume","family":"Voiriot","sequence":"first","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Service de Re\u0301animation me\u0301dico-chirurgicale, H\u00f4pital Tenon, H\u00f4pitaux Universitaires de l\u2019Est Parisien, 75020 Paris, France"},{"name":"Sorbonne Universite\u0301, UFR M\u00e9decine, 75006 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, GRC CARMAS, Universit\u00e9 Paris Est, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Philippot","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Service de Re\u0301animation me\u0301dico-chirurgicale, H\u00f4pital Tenon, H\u00f4pitaux Universitaires de l\u2019Est Parisien, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Elabbadi","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Service de Re\u0301animation me\u0301dico-chirurgicale, H\u00f4pital Tenon, H\u00f4pitaux Universitaires de l\u2019Est Parisien, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Elbim","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Centre de Recherche Saint-Antoine, Team \u201cImmune System, Neuroinflammation and Neurodegenerative Diseases\u201d, H\u00f4pital Saint-Antoine, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Chalumeau","sequence":"additional","affiliation":[{"name":"UMR 1153 Epidemiology and Biostatistics Sorbonne Paris Cit\u00e9 Center (CRESS), Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOP\u00e9), Paris Descartes University, 75014 Paris, France"},{"name":"Department of General Pediatrics and Pediatric Infectious Diseases, Necker hospital for Sick Children, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris Descartes, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Fartoukh","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Service de Re\u0301animation me\u0301dico-chirurgicale, H\u00f4pital Tenon, H\u00f4pitaux Universitaires de l\u2019Est Parisien, 75020 Paris, France"},{"name":"Sorbonne Universite\u0301, UFR M\u00e9decine, 75006 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, GRC CARMAS, Universit\u00e9 Paris Est, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1034\/j.1399-3003.2000.15d21.x","article-title":"Epidemiology of community-acquired pneumonia in adults: A population-based study","volume":"15","author":"Almirall","year":"2000","journal-title":"Eur. Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/thx.2009.129502","article-title":"Clinical and economic burden of community-acquired pneumonia among adults in Europe","volume":"67","author":"Welte","year":"2012","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15010","DOI":"10.1038\/npjpcrm.2015.10","article-title":"Suspected community-acquired pneumonia in an ambulatory setting (CAPA): A French prospective observational cohort study in general practice","volume":"25","author":"Partouche","year":"2015","journal-title":"NPJ Prim. Care Respir. Med."},{"key":"ref_4","first-page":"163","article-title":"Prise en charge des infections respiratoires basses en m\u00e9decine g\u00e9n\u00e9rale en France","volume":"18","author":"Taytard","year":"2001","journal-title":"Revue des Maladies Respiratoires"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1183\/09031936.02.00219102","article-title":"Management of lower respiratory tract infections by French general practitioners: The AIR II study","volume":"19","author":"Raherison","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S0954-6111(03)00030-1","article-title":"Lower respiratory tract infections in adults: Non-antibiotic prescriptions by GPs","volume":"97","author":"Raherison","year":"2003","journal-title":"Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1001\/jamainternmed.2015.8581","article-title":"Changes in Prescription and Over-the-Counter Medication and Dietary Supplement Use Among Older Adults in the United States, 2005 vs. 2011","volume":"176","author":"Qato","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1186\/s12889-018-6019-z","article-title":"Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The MCC-Spain study","volume":"18","author":"Amiano","year":"2018","journal-title":"BMC Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1086\/511159","article-title":"Infectious Diseases Society of America\/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults","volume":"44","author":"Mandell","year":"2007","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/thx.2009.121434","article-title":"BTS guidelines for the management of community acquired pneumonia in adults: Update 2009","volume":"64","author":"Lim","year":"2009","journal-title":"Thorax"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1469-0691.2011.03602.x","article-title":"Guidelines for the management of adult lower respiratory tract infections - Full version","volume":"17","author":"Woodhead","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kim, S.Y., Chang, Y.-J., Cho, H.M., Hwang, Y.-W., and Moon, Y.S. (2015). Non-steroidal anti-inflammatory drugs for the common cold. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD006362.pub4"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1365-2710.2006.00754.x","article-title":"Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu","volume":"31","author":"Eccles","year":"2006","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1056\/NEJMra074111","article-title":"Acute lower respiratory tract infection","volume":"358","author":"Mizgerd","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_15","first-page":"237","article-title":"Prostaglandins E as modulators of the immune response","volume":"7","author":"Chouaib","year":"1988","journal-title":"Lymphokine Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0006-2952(84)90228-4","article-title":"Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo","volume":"33","author":"Kaplan","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/rheumatology\/29.5.363","article-title":"Effect of non-steroidal anti-inflammatory drugs on neutrophil chemotaxis--An in vitro and in vivo study","volume":"29","author":"Ip","year":"1990","journal-title":"Br. J. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/0006-2952(84)90661-0","article-title":"In vivo interaction of nonsteroidal anti-inflammatory drugs on the locomotion of neutrophils elicited by acute non-specific inflammations in the rat--effect of indomethacin, ibuprofen and flurbiprofen","volume":"33","author":"Perianin","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_19","first-page":"234","article-title":"Ibuprofen modulates NF-kB activity but not IL-8 production in cystic fibrosis respiratory epithelial cells","volume":"79","author":"Dauletbaev","year":"2010","journal-title":"Respir. Int. Rev. Thorac. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1111\/bph.13464","article-title":"New use for an old drug: COX-independent anti-inflammatory effects of sulindac in models of cystic fibrosis","volume":"173","author":"Rocca","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1164\/ajrccm\/141.1.186","article-title":"Ibuprofen Attenuates the Inflammatory Response to Pseudomonas aeruginosa in a Rat Model of Chronic Pulmonary Infection: Implications for Antiinflammatory Therapy in Cystic Fibrosis1-4","volume":"141","author":"Konstan","year":"1990","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/infdis\/159.2.232","article-title":"Piroxicam treatment protects mice from lethal pulmonary challenge with Pseudomonas aeruginosa","volume":"159","author":"Sordelli","year":"1989","journal-title":"J. Infect. Dis."},{"key":"ref_23","first-page":"118","article-title":"Ibuprofen modifies the inflammatory response of the murine lung to Pseudomonas aeruginosa","volume":"67","author":"Sordelli","year":"1985","journal-title":"Eur. J. Respir. Dis."},{"key":"ref_24","first-page":"857","article-title":"Aspirin impairs antibacterial mechanisms in experimental pneumococcal pneumonia","volume":"130","author":"Esposito","year":"1984","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1476-5381.1977.tb08402.x","article-title":"Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog","volume":"61","author":"Fletcher","year":"1977","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","first-page":"821","article-title":"Indomethacin improves survival after endotoxin in baboons","volume":"7","author":"Fletcher","year":"1980","journal-title":"Adv. Prostaglandin Thromboxane Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1476-5381.1975.tb07384.x","article-title":"E. coli endotoxin shock in the cat; treatment with indomethacin","volume":"53","author":"Parratt","year":"1975","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1152\/jappl.1984.56.5.1246","article-title":"Prostaglandin I2 supports blood flow to hypoxic alveoli in anesthetized dogs","volume":"56","author":"Sprague","year":"1984","journal-title":"J. Appl. Physiol."},{"key":"ref_29","first-page":"1829","article-title":"Effect of cyclooxygenase blockade on gas exchange and hemodynamics in Pseudomonas pneumonia","volume":"63","author":"Hanly","year":"1987","journal-title":"J. Appl. Physiol. Bethesda Md 1985"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1378\/chest.111.4.1094","article-title":"Effect of acetylsalicylic acid on pulmonary gas exchange in patients with severe pneumonia: A pilot study","volume":"111","author":"Ferrer","year":"1997","journal-title":"Chest"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0140-6736(87)91727-2","article-title":"Effect of indomethacin on arterial oxygenation in critically ill patients with severe bacterial pneumonia","volume":"1","author":"Hanly","year":"1987","journal-title":"Lancet Lond. Engl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1056\/NEJM199703273361303","article-title":"The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group","volume":"336","author":"Bernard","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/89759","article-title":"Lipid mediator class switching during acute inflammation: signals in resolution","volume":"2","author":"Levy","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_35","first-page":"5033","article-title":"Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury","volume":"174","author":"Fukunaga","year":"2005","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/9550","article-title":"Inducible cyclooxygenase may have anti-inflammatory properties","volume":"5","author":"Gilroy","year":"1999","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1136\/bmj.290.6484.1786","article-title":"Haemolytic streptococcal gangrene and non-steroidal anti-inflammatory drugs","volume":"290","author":"Saada","year":"1985","journal-title":"Br. Med. J. Clin. Res. Ed"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/01.md.0000085060.63483.bb","article-title":"Assessing the relationship between the use of nonsteroidal antiinflammatory drugs and necrotizing fasciitis caused by group A streptococcus","volume":"82","author":"Aronoff","year":"2003","journal-title":"Medicine (Baltimore)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1365-2230.2007.02652.x","article-title":"French Network of Pharmacovigilance Centres Severe necrotizing soft-tissue infections and nonsteroidal anti-inflammatory drugs","volume":"33","author":"Souyri","year":"2008","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0399-077X(00)89136-2","article-title":"\u00c9rysip\u00e8le et fasciite n\u00e9crosante: prise en charge Texte court","volume":"30","author":"Avril","year":"2000","journal-title":"M\u00e9decine Mal. Infect."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1365-2125.2007.02997.x","article-title":"Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease","volume":"65","author":"Mikaeloff","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10096-016-2770-1","article-title":"Is there an association between prior anti-inflammatory drug exposure and occurrence of peritonsillar abscess (PTA)? A national multicenter prospective observational case-control study","volume":"36","author":"Lepelletier","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ejim.2017.03.004","article-title":"Bacterial infections and NSAIDs exposure? Seek septic complications","volume":"41","author":"Boutoille","year":"2017","journal-title":"Eur. J. Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/cc7766","article-title":"A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock","volume":"13","author":"Legras","year":"2009","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_45","first-page":"861","article-title":"Prevalence and risk factors of suppurative complications in children with pneumonia","volume":"99","author":"Desrumaux","year":"2010","journal-title":"Acta Paediatr. Oslo Nor. 1992"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1086\/338460","article-title":"An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations","volume":"34","author":"Byington","year":"2002","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1378\/chest.09-3102","article-title":"Nonsteroidal Antiinflammatory Drugs May Affect the Presentation and Course of Community-Acquired Pneumonia","volume":"139","author":"Voiriot","year":"2011","journal-title":"Chest"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.jcrc.2014.05.021","article-title":"Risks of nonsteroidal antiinflammatory drugs in undiagnosed intensive care unit pneumococcal pneumonia: younger and more severely affected patients","volume":"29","author":"Messika","year":"2014","journal-title":"J. Crit. Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/ppul.23041","article-title":"North East of England Pediatric Respiratory Infection Study Group Newcastle upon Tyne, UK Risk factors for the development of pleural empyema in children","volume":"50","author":"Elemraid","year":"2015","journal-title":"Pediatr. Pulmonol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jpeds.2016.05.025","article-title":"Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study","volume":"175","author":"Ferroni","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.rmed.2016.12.005","article-title":"Prehospital NSAIDs use prolong hospitalization in patients with pleuro-pulmonary infection","volume":"123","author":"Kotsiou","year":"2017","journal-title":"Respir. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00408-016-9973-1","article-title":"Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study","volume":"195","author":"Basille","year":"2017","journal-title":"Lung"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/crj.12524","article-title":"Risk factors for local complications in children with community-acquired pneumonia","volume":"12","author":"Krenke","year":"2018","journal-title":"Clin. Respir. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1164\/rccm.201802-0229LE","article-title":"Non-steroidal Anti-inflammatory Drug Use and Clinical Outcomes of Community-acquired Pneumonia","volume":"198","author":"Basille","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0002-9343(80)90363-0","article-title":"The problem of \u201cprotopathic bias\u201d in case-control studies","volume":"68","author":"Horwitz","year":"1980","journal-title":"Am. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/6\/786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:55:44Z","timestamp":1760187344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/6\/786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,3]]},"references-count":55,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["jcm8060786"],"URL":"https:\/\/doi.org\/10.3390\/jcm8060786","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,3]]}}}