Nonsteroidal Antiinflammatory Drug Use and Clinical Outcomes of Community-acquired Pneumonia

Basille, Damien; Thomsen, Reimar Wernich; Madsen, Morten; Duhaut, P.; Andréjak, Claire; Jounieaux, Vincent; Sørensen, Henrik Toft

doi:10.1164/rccm.201802-0229le

Cited by 30 publications

(57 citation statements)

References 9 publications

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“…Relevant to the study of COVID-19, this has previously been shown to be a particular concern in the association between recent use of NSAIDs and pneumonia complications. 16,17 Similar patterns could be hypothesised for, for example, other analgesics, antibiotics, and inhaled glucocorticoids.…”

Section: Consideration #5: How To Define Exposure?mentioning

confidence: 60%

Considerations for pharmacoepidemiological analyses in the SARS‐CoV‐2 pandemic

Pottegård

Kurz

Moore

et al. 2020

Pharmacoepidemiology and Drug

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The coronavirus disease 2019 (COVID-19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses; however, appropriate design and conduct of pharmacoepidemiologic studies are needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritise some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to "real-time epidemiology" during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6 ) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting.

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Section: Consideration #5: How To Define Exposure?mentioning

confidence: 60%

Considerations for pharmacoepidemiological analyses in the SARS‐CoV‐2 pandemic

Pottegård

Kurz

Moore

et al. 2020

Pharmacoepidemiology and Drug

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“…This included 269 from MEDLINE, 1214 from EMBASE, and 25 studies from COCHRANE CENTRAL database, and 4 studies from searching reference lists. Twelve potential publications that met the inclusion criteria after title and abstract review were identified 3–12, 19, 20 . After full text review, two additional studies with no active comparator (case series) were excluded (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…There were five nested case‐control studies, 4, 5, 7, 8, 12 three cohort studies, 3, 6, 11 and two population‐based case‐control studies 9, 10 (Table ). In total, the studies included 59,724 adults across 5 of the studies (range = 57–59,250) 3, 6, 7, 11, 12 . and 1217 children across 5 studies (range = 148–540) 4, 5, 8–10 .…”

Section: Resultsmentioning

confidence: 99%

“…and 1217 children across 5 studies (range = 148–540) 4, 5, 8–10 . Four studies examined ibuprofen use, 4, 5, 8, 9 whereas six studies assessed all NSAIDs 3, 6, 7, 10–12 (Table ). All 10 studies 3–12 examined the use of NSAIDs and measured their effect on the risk of complications of pneumonia when compared with no use of NSAIDs.…”

Section: Resultsmentioning

confidence: 99%

“…However, recent concerns have been raised about the safety of NSAIDS, specifically ibuprofen in patients with lower respiratory tract infections 2 . Observational studies have indicated an increased risk of pneumonia complications associated with NSAIDs in this patient population 3–12 . It has also been hypothesized that NSAIDs, like ibuprofen, can induce proinflammatory cascades that may increase inflammatory response within the lungs, as indicated by greater white blood cell migration, particularly neutrophils 13, 14 …”

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Non‐steroidal Anti‐inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review

et al. 2020

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There have been concerns regarding the safety of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with respiratory infections. However, to date, the quality of the evidence has not been systematically assessed. The purpose of this systematic review was to evaluate the role of NSAIDs on pneumonia complications. OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Google Scholar were searched. Studies that examined pneumonia complications in patients who had taken NSAIDs before onset of symptoms were identified. Quality assessment was conducted using the Risk of Bias in Non‐randomized Studies – of Interventions (ROBINS‐I) assessment tool, which was adapted to include biases that were pertinent to this question. The search strategy identified 1721 potential studies through the 5 primary databases and searching reference lists. Of these, 10 studies met the inclusion criteria, including 5 nested case‐control studies, 2 population‐based case‐control studies, and 3 cohort studies. In total, 59,724 adults were included from 4 of the studies (range = 57–59,250) and 1217 children from 5 studies (range = 148–540). All studies demonstrated a positive association; in adults (odds ratio/risk ratio range = 1.8–8.1) and children (odds ratio/risk ratio range = 1.9–6.8). Studies were limited by moderate or serious risk of confounding bias, exposure misclassification, and protopathic biases and sparse data bias. The results of this review demonstrate that published studies on the effect of NSAIDs use and risk of pneumonia complications are subject to a number of biases. These results should not be extrapolated as evidence of harm for NSAIDs, including ibuprofen, in respiratory ailments but highlight the need for more methodologically robust studies to evaluate this potential relationship.

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Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza

et al. 2020

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IMPORTANCE During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. OBJECTIVE To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. DESIGN, SETTING, AND PARTICIPANTS This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. EXPOSURES Prescription fill of an NSAID within 60 days before admission. MAIN OUTCOMES AND MEASURES Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. RESULTS A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD,-0.7%; 95% CI,-3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI,-0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI,-2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). CONCLUSIONS AND RELEVANCE In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.

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Nonsteroidal Antiinflammatory Drug Use and Clinical Outcomes of Community-acquired Pneumonia

Cited by 30 publications

References 9 publications

Considerations for pharmacoepidemiological analyses in the SARS‐CoV‐2 pandemic

Considerations for pharmacoepidemiological analyses in the SARS‐CoV‐2 pandemic

Non‐steroidal Anti‐inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review

Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza

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