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S45 MUC5B Genotype does not influence cough severity in IPF
  1. P Saunders1,
  2. CJ Stock1,
  3. PL Molyneaux1,
  4. M Kokosi1,
  5. S Kingston1,
  6. MG Belvisi2,
  7. AU Wells1,
  8. EA Renzoni1,
  9. TM Maher1
  1. 1Royal Brompton and Harefield NHS Foundation Trust, London, UK
  2. 2Imperial College London, London, UK

Abstract

Introduction Cough is a disabling symptom in IPF which causes significant reduction in quality of life. The mechanisms underlying cough in fibrotic lung disease are not well understood. Polymorphisms in the rs35105950 promoter region of the MUC5B gene have been shown to relate to risk of developing IPF and, in those with disease, have been shown to increase mucin expression in the small airways. A previous small study linked carriage of the minor T allele at rs35105950 with heightened cough in IPF. We sought to test this observation in a larger cohort of prospectively recruited individuals with IPF.

Method MUC5B genotyping was performed on 117 prospectively recruited individuals with IPF. All subjects completed the Leicester Cough Questionnaire and full lung function at the time of their blood draw. Survival time from enrolment was censored at 1st May 2015. Statistical analyses were performed using SAS software.

Results The mean age of subjects at enrolment was 68 ± 8.4 with 79% being male. Subjects had, on average, moderately severe disease with mean FVC 73.9 ± 19.7% predicted and DLco 41.7 ± 18.1% predicted. At baseline, the median (IQR) LCQ score was 16.0 (11.6–18.6) points. 43 subjects (36.8%) were homozygous at rs35105950 for the G allele, 62 (53.0%) were heterozygous and 12 (11.1%) were homozygous for the T allele. Despite a trend towards worse disease at baseline, homozygosity of the T allele was correlated with a significant survival advantage (422 days compared to GG, p = 0.0063). There was, however, no difference on univariate analysis in LCQ cough severity between groups based on MUC5B genotype (GG 14.6 ± 4.5, GT 15.3 ± 3.9 and TT 15.1 ± 3.5, p = 0.70). This finding did not change when correction was applied for baseline disease severity.

Conclusions The severity of self-reported cough is worse in IPF than in other respiratory diseases. In contrast to one previous small study of 68 subjects, there is no relationship between patient reported cough and MUC5B genotype in our cohort. It therefore seems unlikely that the mechanism behind cough in fibrosing lung disease is related to mucin production. Further studies are required to determine the mechanisms underlying the heightened cough response observed in IPF.

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