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.

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    • "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. "
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    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.
    Environmental Health Perspectives 10/2015; DOI:10.1289/ehp.1509851 · 7.98 Impact Factor
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    • "compared with children who received paracetamol [49]. Paracetamol use during pregnancy has been implicated in asthma development and the increasing incidence of asthma in adults and children in epidemiologic, observational and pathophysiologic studies (reviewed in [50–52] and more recently in a prospective birth cohort study [53]). Given the widespread use of paracetamol in children, there has been a call for causation to be proved or disproved in adequately powered placebo-controlled trials [54], and clearly more research is required in this field. "
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    ABSTRACT: Fever is a common symptom of childhood infections that in itself does not require treatment. The UK's National Institute for Health and Care Excellence (NICE) advises home-based antipyretic treatment for low-risk feverish children only if the child appears distressed. The recommended antipyretics are ibuprofen or paracetamol (acetaminophen). They are equally recommended for the distressed, feverish child; therefore, healthcare professionals, parents and caregivers need to decide which of these agents to administer if the child is distressed. This narrative literature review examines recent data on ibuprofen and paracetamol in feverish children to determine any clinically relevant differences between these agents. The data suggest that these agents have similar safety profiles in this setting and in the absence of underlying health issues, ibuprofen seems to be more effective than paracetamol at reducing NICE's treatment criterion, 'distress' (as assessed by discomfort levels, symptom relief, and general behavior).
    Drugs in R & D 06/2014; 14(2). DOI:10.1007/s40268-014-0052-x · 1.71 Impact Factor
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    • "The argumentative basis for a causal role of early childhood use of paracetamol in asthma development has recently been summarized [69] (cited in italics below), allowing a point-by-point inspection of its soundness. "
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    ABSTRACT: Aim: The rising prevalence of bronchial asthma has led to world-wide efforts to understand and stem this development. Cross-sectional studies appear to show that early childhood use of antibiotics may be an important contributory factor, with paracetamol as an additional suspected cause. However, mounting evidence, which is reviewed here, points to various confounding factors as the major reasons for these reported associations. Methods: PubMed and EMBASE were systematically searched for studies on associations between antibiotics and/or paracetamol with asthma and/or wheezing, published up to November 2012. A total of 64 pertinent studies were identified, 35 focusing on antibiotics, 19 on paracetamol, and ten addressing both antibiotics and paracetamol, bringing the number of relevant datasets to 74. Results: Numerous studies were cross-sectional and made no adjustment for the indication of antibiotics or paracetamol; consequently, they were unable to dismiss possible confounding by indication. Where such adjustments could be performed (mostly in longitudinal studies), they substantially weakened or entirely eliminated the association with asthma or asthma surrogates present in the unadjusted data. Conclusion: The weight of evidence of the collected studies in our review strongly suggests that the association of antibiotics with childhood asthma reflects various forms of bias, the most prominent of which is confounding by indication. Recent studies and meta-analyses support the same conclusion for paracetamol. Truly indicated antibiotics should not be withheld from infants or young children for fears they might develop asthma. Likewise, there is no sound reason to replace paracetamol as the preferred pain relief and fever medication in this age group.
    European Journal of Clinical Pharmacology 01/2013; 69(6). DOI:10.1007/s00228-012-1463-7 · 2.97 Impact Factor
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