Severe Occupational Asthma : Insights From a Multicenter European Cohort

BACKGROUND: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. OBJECTIVE: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. METHODS: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction. RESULTS: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97). CONCLUSIONS: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease. (C) 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & ImmunologyPeer reviewe

Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study.

Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n = 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. Most subjects with QAC-induced OA were working in the health care sector (n = 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001). This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents

Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms.

Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. In this retrospective multicenter study, OEB was defined by: 1) a fall in FEV <15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness (NSBH) both before after the SIC; and 2) a post-challenge increase in sputum eosinophils ≥3%. The subjects who fulfilled these criteria were compared to 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline NSBH. An isolated increase in post-challenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in FeNO in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, while the specificity was high (90% to 97%). This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms in order to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB

Phenotyping occupational asthma caused by acrylates in a multicentre cohort study.

BACKGROUND While acrylates are well-known skin sensitisers, they are not classified as respiratory sensitisers although several cases of acrylate-induced occupational asthma (OA) have been reported. OBJECTIVES The aim of this study was to evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents. METHODS Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analysed in an international, multicentre, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n= 55) or other LMW agents (n=418) including isocyanates (n=125). RESULTS Acrylate-containing glues were the most prevalent products and industrial manufacturing, dental work and beauty care were typical occupations causing OA. Work related rhinitis was more common in acrylate than isocyanate-induced asthma (p<0.001). The increase in post-challenge fractional exhaled nitric oxide (FeNO) was significantly greater in acrylate-induced OA (26.0, 8.2-38.0 ppb) than in OA induced by other LMW agents (3.0, -1.0-10.0 ppb, p<0.001) or isocyanates (5.0, 2.0-16.0 ppb, p=0.010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a post-challenge increase in FeNO (≥17.5 ppb). CONCLUSIONS Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis and exposure-related increases in FeNO, suggesting that acrylates may induce asthma through different immunological mechanisms than other LMW agents. Our findings reinforce the need for a re-evaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential