BACKGROUND: 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 shows distinct phenotypic profiles. METHODS: 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. RESULTS: 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 postchallenge increase in fractional nitric oxide. CONCLUSION: 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.

Allergy and Immunology Unit Istituti Clinici Scientifici Maugeri IRCCS Pavia Italy

Cardio Thoracic and Vascular Department University of Pisa Pisa Italy

Department of Allergy Fundacion Jimenez Dıaz and CIBER de Enfermedades Respiratorias Madrid Spain

Department of Allergy Hospital La Paz Institute for Health Research Madrid Spain

Department of Allergy Skin and Allergy Hospital Helsinki University Central Hospital Helsinki Finland

Department of Chest Medicine Centre Hospitalier Universitaire UCL Namur Université Catholique de Louvain Yvoir Belgium

Department of Medicine Section of Occupational Medicine Respiratory Diseases and Occupational and Environmental Toxicology University of Perugia Perugia Italy

Department of Occupational and Environmental Medicine Royal Brompton Hospital and Imperial College Royal Brompton and Harefield NHS Foundation Trust London UK

Department of Occupational Diseases and Environmental Health Nofer Institute of Occupational Medicine Lodz Poland

Department of Occupational Medicine 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Occupational Medicine Haukeland University Hospital Bergen Norway

Department of Public Health Experimental and Forensic Medicine University of Pavia Pavia Italy

Department of Pulmonary Medicine and Occupational Medicine Odense University Hospital Odense Denmark

Department of Respiratory Medicine North Manchester General Hospital Manchester UK

Division of Asthma and Allergy Department of Chest Diseases University Hospital of Strasbourg and Fédération de Médecine translationnelle Strasbourg University Strasbourg France

Institute for Occupational and Maritime Medicine University Medical Center Hamburg Eppendorf Hamburg Germany

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Ruhr University Bochum Germany

Occcupational Medicine Finnish Institute of Occupational Health Helsinki Finland

Occupational Lung Disease Unit Birmingham Heartlands Hospital Birmingham UK

Pôle de Santé Publique Strasbourg University Strasbourg France

Servei Pneumologia Hospital Vall d'Hebron Universitat Autonoma de Barcelona and CIBER de Enfermedades Respiratorias Barcelona Spain

Unit of Occupational Medicine and Public Health University of Padova Padova Italy

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