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      Wheezing after the use of acetaminophen and or ibuprofen for first episode of bronchiolitis or respiratory tract infection

      research-article
      Author(s): 1 , * , 2
      Editor(s):
      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Background

          Bronchiolitis sometimes triggers the development of subsequent recurrent wheezing. Treatment with either acetaminophen or ibuprofen during the initial episode may affect the occurrence of subsequent wheezing.

          Materials and methods

          We did a retrospective study comparing the effect of prescribing acetaminophen, ibuprofen, or neither for a first episode of bronchiolitis on medical attendances for subsequent wheezing in infants younger than 12 months. We created our cohorts using California Medicaid data from 2003 to 2010. We used propensity score derived inverse probability weights to adjust for non-random drug assignment. We used robust negative binomial regression to model incident rate ratios (IRR) for medical attendances at 365, 30, and 14-day follow-up. We did similar analyses for the effect of antipyretics for a first medically attended upper respiratory tract infection (URI) on subsequent wheezing.

          Results

          Compared with no antipyretic, treatment with acetaminophen or ibuprofen for a first episode of bronchiolitis was associated with decreased wheezing at 365-day follow-up (IRR 0.18, 95% CI 0.15–0.22), and ibuprofen plus acetaminophen over ibuprofen (IRR at 0.12, 95% CI 0.05–0.32). The results were similar at 30 and 14-day follow-up. Ibuprofen alone and ibuprofen plus acetaminophen were associated with decreased visits for subsequent wheezing at 365-day (IRR 0.79, 95% CI 0.68–0.92), but not earlier timepoints, when compared with acetaminophen. A smaller effect was seen for ibuprofen at one year if prescribed for a URI (IRR 0.87, 95% CI 0.76–1.00) but not at earlier follow-up.

          Conclusion

          Children who are prescribed antipyretics for a first episode of bronchiolitis may have less subsequent wheezing than those who are not. We found fewer visits for subsequent wheezing for those prescribed ibuprofen, and ibuprofen combined with acetaminophen, compared with acetaminophen alone.

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          Most cited references24

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          :{unav)

          Donald B Rubin (2001)
          Health Services and Outcomes Research Methodology, 2(3/4), 169-188
          Article 0 comments Cited 185 times – based on 0 reviews     Review now
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            Assessing the sensitivity of regression results to unmeasured confounders in observational studies.

            R Kronmal, Y. Lin, B Psaty (1998)
            This paper presents a general approach for assessing the sensitivity of the point and interval estimates of the primary exposure effect in an observational study to the residual confounding effects of unmeasured variable after adjusting for measured covariates. The proposed method assumes that the true exposure effect can be represented in a regression model that includes the exposure indicator as well as the measured and unmeasured confounders. One can use the corresponding reduced model that omits the unmeasured confounder to make statistical inferences about the true exposure effect by specifying the distributions of the unmeasured confounder in the exposed and unexposed groups along with the effects of the unmeasured confounder on the outcome variable. Under certain conditions, there exists a simple algebraic relationship between the true exposure effect in the full model and the apparent exposure effect in the reduced model. One can then estimate the true exposure effect by making a simple adjustment to the point and interval estimates of the apparent exposure effect obtained from standard software or published reports. The proposed method handles both binary response and censored survival time data, accommodates any study design, and allows the unmeasured confounder to be discrete or normally distributed. We describe applications on two major medical studies.
            Article 0 comments Cited 82 times – based on 0 reviews     Review now
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              Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers.

              Teal C. Burrell, Alison N. Graham, Marlis Douglas … (1990)
              A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups.
              Article 0 comments Cited 57 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Paul Walsh:
                ORCID: http://orcid.org/0000-0003-4059-7115
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Stephen J. Rothenberg: Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Lamberto Manzoli: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 13 September 2018
                Publication date Collection: 2018
                Volume: 13
                Issue: 9
                Electronic Location Identifier: e0203770
                Affiliations
                [1 ] Pediatric Emergency Medicine, Sutter Medical Center, Sacramento, CA, United States of America
                [2 ] Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Cuernavaca, Morelos, Mexico
                Universita degli Studi di Ferrara, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4059-7115
                Article
                Publisher ID: PONE-D-18-06746
                DOI: 10.1371/journal.pone.0203770
                PMC ID: 6136746
                PubMed ID: 30212517
                SO-VID: 638f9c98-d15f-4603-ace6-7258c2e35511
                Copyright © © 2018 Walsh, Rothenberg
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 7 April 2018
                Date accepted : 27 August 2018
                Page count
                Figures: 2, Tables: 7, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: 5K12HL108964
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-4059-7115
                Funded by: Pediatric Emergency Medicine Research Foundation
                Award ID: na
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-4059-7115
                Pediatric Emergency Research foundation contributed software used for analysis. The NHLBI (5K12HL108964) provided partial salary support for part of the time that this study was conducted. These had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Bronchiolitis
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Asthma
                Subject: People and Places
                Subject: Population Groupings
                Subject: Age Groups
                Subject: Children
                Subject: Infants
                Subject: People and Places
                Subject: Population Groupings
                Subject: Families
                Subject: Children
                Subject: Infants
                Subject: Medicine and Health Sciences
                Subject: Pediatrics
                Subject: Medicine and health sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Analgesics
                Subject: NSAIDs
                Subject: Medicine and health sciences
                Subject: Pain management
                Subject: Analgesics
                Subject: NSAIDs
                Subject: People and Places
                Subject: Population Groupings
                Subject: Age Groups
                Subject: Children
                Subject: People and Places
                Subject: Population Groupings
                Subject: Families
                Subject: Children
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Respiratory Infections
                Subject: Upper Respiratory Tract Infections
                Subject: Medicine and Health Sciences
                Subject: Pharmaceutics
                Subject: Drug Therapy
                Subject: Drug Administration
                Custom metadata
                Data Availability This study uses third party data and others could access these data in the same manner as the authors. Because of the potential for re-identification of individuals by combining the data with other publicly available sources, the State of California Committee for Protection of Human Subjects has ruled that these data cannot be made publicly available. These data can be obtained by direct application to both DHCS and State of California Committee for Protection of Human Subjects subject to both agencies’ approval. This process is outlined in The Information Practices Act and on the websites of the two agencies: https://www.oshpd.ca.gov/Boards/CPHS/, data access information can also be gained from HCSDRC@ 123456dhcs.ca.gov . This information can be obtained after obtaining the required permissions from HCSDRC@ 123456dhcs.ca.gov or via mail at: Department of Health Care Services, Information Management Division, MS 0021, P.O. Box 997413, Sacramento, CA 95899-7413, Attn: Data and Research Committee. This information was obtained under the terms of the California Information Practices Act.

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