What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures study

Reynolds, C. J.; Sisodia, R.; Barber, C.; Minelli, C.; De Matteis, S.; Moffatt, M.; Cherrie, J.; Newman Taylor, A.; Cullinan, P.

Rationale: Asbestos is posited to cause otherwise 'idiopathic' pulmonary fibrosis (IPF); establishing this has important diagnostic and therapeutic implications. Objectives: To determine the association between occupational asbestos exposure and IPF; to investigate interaction with MUC5B rs35705950 genotype. Methods: Multi-centre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 United Kingdom hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was measured using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs3570950 was investigated using a genetic dominant model. Measurements and Main Results: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls, had cumulative exposure estimates [≥] 25 fibre/ml.years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1(95%CI 0.8-1.4; p=0.6) and there was no gene-environment interaction (p=0.2). Ever smoking was associated with IPF, OR 1.4 (95%CI 1-1.9; p=0.04). When stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs3570950. Conclusions: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. However, exposure to asbestos and smoking interact to increase IPF risk in carriers of the minor allele of MUC5B rs3570950. Clinical trial registered with www.clinicaltrials.gov (NCT03211507).