Occupational exposures , smoking and airway 3 inflammation in refractory asthma

10 Background: The influence of occupation and ex/passive smoking on inflammatory phenotype is not well 11 understood. The aim of this study was to examine the relationship between occupation, past smoking and current 12 passive smoking and airway inflammation in a population of adults with refractory asthma. 13 Methods: Sixty-six participants with refractory asthma were characterised. Occupational exposure to asthma 14 causing or worsening agents were identified with an asthma-specific job exposure matrix. Exposure to passive 15 cigarette smoke was determined by questionnaire and exhaled carbon monoxide assessment. The carbon content 16 of macrophages was assessed in a sub-group of participants. 17 Results: Nineteen participants had smoked previously with low smoking pack years (median 1.7 years). Ex-smokers 18 more commonly lived with a current smoker (26% vs. 9%, p = 0.11) and were more likely to allow smoking inside 19 their home (26% vs. 4%, p = 0.02) compared to never smokers. Twenty participants had occupations with an identified 20 exposure risk to an asthmagen; thirteen had exposures to irritants such as motor vehicle exhaust and environmental 21 tobacco smoke. Sputum neutrophils were elevated in participants with asthma who had occupational exposures, 22 particularly those who were diagnosed with asthma at a more than 30 years of age. 23 Conclusions: Sputum neutrophils are elevated in refractory asthma with exposure to occupational asthmagens. In 24 addition to older age, exposure to both environmental and occupational particulate matter may contribute to the 25 presence of neutrophilic asthma. This may help explain asthma heterogeneity and geographical variations in airway 26 inflammatory phenotypes in asthma.