The Association of Acetaminophen and Asthma Prevalence and Severity

Department of Pediatrics, Akron Children's Hospital, Akron, OH 44308, USA.
PEDIATRICS (Impact Factor: 5.47). 11/2011; 128(6):1181-5. DOI: 10.1542/peds.2011-1106
Source: PubMed


The epidemiologic association between acetaminophen use and asthma prevalence and severity in children and adults is well established. A variety of observations suggest that acetaminophen use has contributed to the recent increase in asthma prevalence in children: (1) the strength of the association; (2) the consistency of the association across age, geography, and culture; (3) the dose-response relationship; (4) the timing of increased acetaminophen use and the asthma epidemic; (5) the relationship between per-capita sales of acetaminophen and asthma prevalence across countries; (6) the results of a double-blind trial of ibuprofen and acetaminophen for treatment of fever in asthmatic children; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa. Until future studies document the safety of this drug, children with asthma or at risk for asthma should avoid the use of acetaminophen.

7 Reads
  • Source
    • "Multiple epidemiological studies, in both adults and children, reveal an association between the increased APAP use since 1980 and the increased asthma prevalence since that time (Barr et al. 2004; Beasley et al. 2011; Etminan et al. 2009). This has led to the " APAP hypothesis " , specifically that acetaminophen may contribute to asthma causation, perhaps through its oxidant properties (McBride, 2011). This hypothesis is based simply on the observation that both APAP use and asthma prevalence have increased since 1980. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Although it is known that acetaminophen causes oxidative injury in the liver; it is not known if it causes oxidative stress in the respiratory tract. If so, this widely used analgesic may potentiate the adverse effects of oxidant air pollutants. Objectives: The goals of this study were to determine if acetaminophen induces respiratory tract oxidative stress and/or potentiates the oxidative stress and irritant responses to an inhaled oxidant: environmental tobacco smoke (ETS). Methods: Female C57Bl/6J mice were administered acetaminophen (100 mg/kg ip) and/or side stream tobacco smoke (as a surrogate for ETS, 5 mg/m(3) for 10 minutes) with airway oxidative stress being assessed by loss of tissue antioxidants (as estimated by non-protein sulfhydryl, NPSH, levels) and/or induction of oxidant stress response genes. In addition, the effects of acetaminophen on airway irritation reflex responses to ETS were examined by plethysmography. Results: Acetaminophen diminished NPSH in nasal, thoracic extrapulmonary, and lung tissues, and also induced the oxidant stress response genes, glutathione cysteine ligase, catalytic subunit, and NAD(P)H dehydrogenase, quinone 1, in these sites. ETS produced a similar response. The response to acetaminophen plus ETS was equal to or greater than the sum of the responses to either agent alone. Although without effect by itself, acetaminophen greatly increased the reflex irritant response to ETS. Conclusions: Acetaminophen, at supratherapeutic levels, induced oxidative stress throughout the respiratory tract and appeared to potentiate some responses to environmentally relevant ETS exposure in female C57Bl/6J mice. These results highlight the potential for this widely used drug to modulate the responsiveness to oxidant air pollutants.
    Full-text · Article · Oct 2015 · Environmental Health Perspectives
    • "Therefore, a short-term course of NSAIDs has a small risk of precipitating bronchospasm in children with asthma unless they have a history of nasal polyposis or known respiratory intolerance to NSAIDs. Furthermore, one should also exercise caution in children with asthma when prescribing acetaminophen (paracetamol) for postoperative pain as there is emerging evidence of acetaminophen (paracetamol) being a causative agent of asthma[107]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Perioperative respiratory adverse events cause more than three-quarters of all perioperative critical incidents in pediatric anesthesia and approximately half of anesthesia-related cardiac arrests. We can define seven main clinical types of perioperative respiratory adverse events: upper airway obstruction, laryngospasm, bronchospasm, severe persistent cough, apnea, stridor, and oxygen desaturation. Depending on the definitions used for preoperative respiratory adverse events and the cohort of children examined, the incidence varies between 8 and 21 %. This review discusses the recognition and treatment of perioperative respiratory adverse events. Furthermore, it provides guidance on how to identify children who are at increased risk for developing perioperative respiratory adverse events and how to tailor the perioperative anesthetic management for the individual child in order to minimize the risk of perioperative respiratory adverse events.
    No preview · Article · Jun 2015
  • Source
    • "The temporal dynamics of the case also show that cumulative learning around the causal association between paracetamol and asthma emerges and grows through evidence of different types, which demand to be accounted for to provide guidance for action even before a definitive proof is available. The standard clinching way to assess causality Table 1The consistency of interdisciplinary evidence makes the causal association between asthma and acetaminophen plausible enough to change prescription practice (in paediatrics):McBride (2011)1. Strength of the association5758592. "
    [Show abstract] [Hide abstract]
    ABSTRACT: It is increasingly acknowledged both among epidemiologists and regulators that the assessment of pharmaceutical harm requires specific methodological approaches that cannot simply duplicate those developed for testing efficacy. However, this intuition lacks sound epistemic bases and delivers ad hoc advice. This paper explains why the same methods of scientific inference do not fare equally well for efficacy and safety assessment by tracing them back to their epistemic foundations. To illustrate this, Cartwright’s distinction into clinching and vouching methods is adopted and a series of reasons is provided for preferring the latter to the former: (1) the need to take into account all available knowledge and integrate it with incoming data; (2) the awareness that a latent unknown risk may always change the safety profile of a given drug (precautionary principle); (3) cumulative learning over time; (4) requirement of probabilistic causal assessment to allow decision under uncertainty; (5) impartiality; and (6) limited and local information provided by randomised controlled trials. Subsequently, the clinchers/vouchers distinction is applied to a case study concerning the debated causal association between paracetamol and asthma. This study illustrates the tension between implicit epistemologies adopted in evaluating evidence and causality; furthermore, it also shows that discounting causal evidence may be a result of unacknowledged low priors or lack of valid alternative options. We conclude with a presentation of the changing landscape in pharmacology and the trend towards an increased use of Bayesian tools for assessment of harms.
    Full-text · Article · Dec 2014 · Drug Safety
Show more