Occupational Asthma Reference

Vandenplas O, Godet J, Hurdubaea L, Rifflart C, Suojalehto H, Wiszniewska M, Munoz X, Sastre J, Klusackova P, Moore V, Merget R, Talini D, Svanes C, Mason P, dell'Omo M, Cullinan P, Moscato G, Quirce S, Hoyle J, Sherson D, Kauppi P, Preisser A, Meyer N, de Blay F, European network for the PHenotyping of OCcupational ASthma (E-PHOCAS) investigators., Are high- and low-molecular-weight sensitizing agents associated with different clinical phenotypes of occupational asthma?, Allergy, 2018;74:261-272,https://doi.org/10.1111/all.13542

Keywords: OA, SIC, challenge, phenotype, induced sputum, FEV1, Europe

Known Authors

Paul Cullinan, Royal Brompton Hospital, London, UK Paul Cullinan

Olivier Vandenplas, Universite Mont-Goginne, Yvoir Olivier Vandenplas

Vicky Moore, Oasys Vicky Moore

Joaquin Sastre, Fundacion Jimenez Diaz, Madrid Joaquin Sastre

Jennifer Hoyle, North Manchester General Hospital Jennifer Hoyle

Rolf Merget, Bochum Rolf Merget

Giana Moscato, Fondazione Salvatore Maugeri, Pavia Giana Moscato

Xavier Munoz, Barcelona Xavier Munoz

Santiago Quirce, Madrid Santiago Quirce

Hille Suojalehto, Finnish Institute of Occupational Health Hille Suojalehto

Alexandra Preisser, Hamburg Alexandra Preisser

Cecile Svanes, University of Bergen, Norway Cecile Svanes

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High-molecular-weight (HMW) proteins and low-molecular-weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents show distinct phenotypic profiles.

Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n=544) and LMW (n=635) agents.

Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work-related rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]), atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52 [1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07-2.91]) whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater post-challenge increase in fractional nitric oxide.

This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents, There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.

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This is the first result of a collaboration between centres offering specific inhalation testing in the diagnosis of occupational asthma, and contains data of 544 positive tests with high molecular weight agents and 635 tests with low molecular weight agents. As expected high molecular weight agents were associated with more immediate reactions, more eosinophilia, more rhinitis, and more atopy. Late asthmatic reactions were more often seen following exposure to low molecular weight agents, with a third showing late reactions alone showing the need to monitor patients for at least 8 hours after exposure and have facilities for managing late reactions if needed. Induced sputum and FeNO were measured in some, sputum eosinophilia was not different pre challenge in those with and low or high molecular weight agents, an increase in FeNO was more common following high molecular weight challenge.

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