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

Our plain-English summary of What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study, by C.J. Reynolds, R. Sisodia, C. Barber, et al (Occupational and Environmental Medicine, 2023).

The study

• Authors: C.J. Reynolds, R. Sisodia, C. Barber, M. Moffatt, C. Minelli, S. De Matteis, J.W. Cherrie, A. Newman Taylor, P. Cullinan
• Journal: Occupational and Environmental Medicine
• Published: 2023;80(2):97-103
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF, MUC5B rs35705950, is unknown.

Methods: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview 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 rs35705950 was investigated using a genetic dominant model.

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⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, 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 rs35705950.

Conclusion: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of MUC5B rs35705950.

Trial Registration Number: NCT03211507.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This UK case-control study included 494 men newly diagnosed with idiopathic pulmonary fibrosis (IPF) at 21 hospitals between 2017 and 2019, and 466 men of similar age attending outpatient clinics there. Interviewers who did not know who had IPF took lifetime job histories. Jobs were rated for asbestos risk with a job exposure matrix based on pleural mesothelioma deaths by occupation. Men who described asbestos work in enough detail (122 cases, 107 controls) also received numerical exposure estimates. Having ever held a high or medium asbestos-risk job was common (66% of cases, 63% of controls) and was not associated with IPF (odds ratio 1.1, 95% CI 0.8 to 1.4). About 8% of each group had estimated exposure above 25 fibre per ml years. Ever smoking was associated with IPF and interacted with asbestos-risk work (odds ratio 1.9, 95% CI 1 to 3.6). In an analysis not planned in advance, this interaction appeared in carriers of the MUC5B rs35705950 variant (odds ratio 5.4, 95% CI 1.8 to 15.6) but was not significant in non-carriers. The authors concluded that occupational asbestos exposure alone was not associated with IPF.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multicentre, incident case-control study using hospital outpatient controls; analyses were pre-registered (NCT03211507), except the three-way gene-asbestos-smoking interaction analysis
• Who was studied: 960 men in England, Scotland and Wales. Cases were 494 men first diagnosed with IPF at 21 hospitals between 1 February 2017 and 1 October 2019. Controls were 466 men attending randomly selected outpatient clinics at the same hospitals in the same period, frequency-matched on age. Men who had worked outside the UK for 1 year or more were excluded. Median age was 76 for cases and 74 for controls. 902 participants were genotyped for MUC5B rs35705950.
• Exposure: Occupational asbestos exposure, assessed in two ways. First, a job exposure matrix sorted jobs into risk categories (high-risk construction, high-risk non-construction, medium risk industrial, low risk industrial, office), based on occupational proportional mortality ratios for pleural mesothelioma. 'Ever exposed' meant ever having had a high or medium risk job. Second, a source-receptor model estimated cumulative exposure in fibre ml-1 years for the 229 participants (122 cases, 107 controls) whose asbestos-exposed job tasks were recalled in sufficient detail. Smoking and MUC5B rs35705950 genotype were also studied. The article does not name asbestos fiber types.
• Main results:
  • Ever having had a high or medium asbestos exposure risk job was common in both groups: 327 of 494 cases (66%) and 293 of 466 controls (63%) per Table 2. The results text gives 326 and 292.
  • Ever having had a high or medium asbestos exposure risk job was not associated with IPF: adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6), adjusted for age, centre and smoking.
  • Asbestos-exposed job tasks were recalled in enough detail for a numerical estimate in 229 participants (122 cases, 25%; 107 controls, 22%). Of these, 40 cases (33%) and 35 controls (32%) had cumulative estimates above 25 fibre ml-1 years. This is about 8% of each whole group.
  • Ever smoking was associated with IPF in all participants: OR 1.4 (95% CI 1 to 1.9; p=0.04).
  • Ever smoking interacted with ever having had a high or medium asbestos exposure risk job: interaction OR 1.9 (95% CI 1 to 3.6; p=0.04).
  • Carrying one copy of the MUC5B rs35705950 minor allele (GT) was associated with IPF: adjusted OR 4.7 (95% CI 3.5 to 6.3; p<0.001). For two copies (TT) the adjusted OR was 12.0 (95% CI 4.6 to 31.6, p<0.001).
  • There was no evidence of interaction between MUC5B rs35705950 genotype and ever having a high or medium asbestos exposure risk job: adjusted OR 1.3 (95% CI 0.8 to 2.3; p=0.3).
  • In an analysis not specified in advance, the smoking-asbestos job interaction was statistically significant in carriers of the MUC5B rs35705950 minor allele (GT or TT): adjusted OR for interaction 5.4 (95% CI 1.8 to 15.6; p=0.002). It was not significant in GG (wild-type) participants: OR 1.3 (0.5 to 2.9, p=0.6).
  • Sensitivity analyses looked at era (jobs ending before 1980), jobs lasting 5 years or more, a cumulative 'dose' weighting, and men living within 10 km of the recruiting hospital. The authors reported that these did not change the asbestos-IPF findings.
• The authors' conclusion: The authors concluded that a history of occupational asbestos exposure alone was not associated with increased IPF risk in UK men, and that asbestos exposure and smoking interact to increase IPF risk in carriers of the MUC5B rs35705950 minor allele.
• Limitations the authors state:
  • The authors could not examine gene-environment interactions for genetic variants other than MUC5B rs35705950 that are associated with IPF.
  • Comprehensive participation-rate data were lacking because most centres did not complete screening logs. Figures from three centres suggested about 90% participation for cases and 85% for controls.
  • The source-receptor (fibre ml-1 years) estimates depended on participants recalling work with asbestos. The authors called this a possibly insensitive measure but did not think it introduced important bias.
  • The three-way gene-asbestos-smoking interaction analysis was not pre-registered. The authors ran it after finding a significant asbestos-smoking interaction.

Topics

Medical terms in this study, explained in our Lexicon: Idiopathic, Pulmonary Fibrosis, Case-Control Study, Asbestos Exposure, Cumulative Exposure.

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