Normal nonspecific bronchial reactivity excludes occupational asthma?

Abstract

We read with interest the recent study by Pralong et al1Pralong J.A. Lemière C. Rochat T. L'Archevêque J. Labrecque M. Cartier A. Predictive value of nonspecific bronchial responsiveness in occupational asthma.J Allergy Clin Immunol. 2016; 137: 412-416Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar examining the predictive value of methacholine challenge for exposed and unexposed workers in the diagnosis of occupational asthma. The authors conclude that normal methacholine challenge excludes occupational asthma in those currently exposed to a causative agent because of its high sensitivity and negative predictive value, 98.1% and 97.7% respectively; when patients who are currently unexposed are taken into account, overall sensitivity and negative predictive value are reduced (67% and 82%, respectively). These results depend critically on the criteria for a confirmed diagnosis of occupational asthma, the definition of nonspecific bronchial reactivity (NSBR), and any preselection of patients for specific inhalation challenge testing. Canadian Thoracic Society guidelines for occupational asthma2Tarlo S.M. Boulet L.P. Cartier A. Cockcroft D. Cote J. Hargreave F.E. et al.Canadian Thoracic Society guidelines for occupational asthma.Can Respir J. 1998; 5: 289-300Crossref PubMed Scopus (74) Google Scholar have stated that for practical purposes the absence of NSBR excludes the diagnosis of occupational asthma in a symptomatic exposed worker; this is likely to have significantly biased referrals for specific inhalation challenges toward those with significant NSBR. We find many workers with occupational asthma to have normal NSBR while exposed, and after specific inhalation challenge, perhaps because we perform challenges to a much wider range of agents that appear to fulfill the criteria for occupational asthma with sensitization (latent interval, positive specific inhalation challenge to nonirritating levels of exposure, and improvement away from exposure). This incorporates agents such as diesel exhaust and aluminum foundry fumes, which some believe are acting primarily as irritants, but in whom the physiological responses to workplace exposures, including the presence of late asthmatic reactions, appears inseparable from those exposed to generally accepted sensitizing agents.3Burge P.S. Moore V.C. Robertson A.S. Sensitization and irritant-induced occupational asthma with latency are clinically indistinguishable.Occup Med. 2012; 62: 129-133Crossref Scopus (35) Google Scholar In the current study, the molecular weight of the agent causing occupational asthma, either low or high, was not a predictor of NSBR. We would argue that this is unexpected: in a series of 38 patients from our occupational lung disease unit in Birmingham, United Kingdom,4Anees W. Huggins V. Pavord I.D. Robertson A.S. Burge P.S. Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants.Thorax. 2002; 57: 231-236Crossref PubMed Scopus (96) Google Scholar occupational asthma due to low molecular weight agents was predominantly associated with noneosinophilic inflammation, with only 14 of 38 (37%) cases demonstrating sputum eosinophilia (>2.2%) while exposed at work; moreover, noneosinophilic phenotypes showed significantly less NSBR than did eosinophilic phenotypes. This observation is supported by the meta-analysis of the value of NSBR in occupational asthma,5Beach J. Russell K. Blitz S. Hooton N. Spooner C. Lemiere C. et al.A systematic review of the diagnosis of occupational asthma.Chest. 2007; 131: 569-578Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar which showed that pooled estimates of sensitivity are lower for low molecular weight agents than for high molecular weight agents. We believe that NSBR should not be used to exclude patients with work-related asthma symptoms from referral to specialized units and further investigation. Many of these patients have poor health outcomes if left exposed at work. Predictive value of nonspecific bronchial responsiveness in occupational asthmaJournal of Allergy and Clinical ImmunologyVol. 137Issue 2PreviewThe diagnosis of occupational asthma (OA) can be challenging and needs a stepwise approach. However, the predictive value of the methacholine challenge has never been addressed specifically in this context. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 138Issue 4PreviewWe have read with interest the response of Walters et al1 regarding our article.2 We respectfully disagree with the comments made by Walters et al. Full-Text PDF