<i>FUT2</i> genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis.

Abstract

To assess whether <i>FUT2</i> (<i>secretor</i>) genotype affects disease severity and airway infection in patients with non-cystic fibrosis bronchiectasis. Induced sputum samples were obtained from 112 adult patients with high-resolution CT scan-proven bronchiectasis and at least two exacerbations in the previous year, as part of an unrelated randomised control trial. Presence of null <i>FUT2</i> polymorphisms were determined by gene sequencing and verified by endobronchial biopsy histochemical staining. Outcome measures were FEV₁% predicted, exacerbation frequency, and bacterial, fungal and viral components of the microbiota (measured by culture independent approaches). Patients were grouped by <i>FUT2</i> loss-of-function genotype; categorised as non-secretors (n=27, <i>sese</i>), heterozygous secretors (n=54, <i>Sese</i>) or homozygous secretors (n=31, <i>SeSe</i>). FEV₁% was significantly lower in <i>SeSe</i> patients compared with <i>sese</i> patients (mean 61.6 (SD 20.0) vs 74.5 (18.0); p=0.023). Exacerbation frequency was significantly higher in <i>SeSe</i> (mean count 5.77) compared with <i>sese</i> (4.07; p=0.004) and <i>Sese</i> (4.63; p=0.026) genotypes. The time until first exacerbation was significantly shorter in <i>SeSe</i> compared with <i>Sese</i> (HR=0.571 (95% CI 0.343 to 0.950); p=0.031), with a similar trend for <i>sese</i> patients (HR=0.577 (0.311 to 1.07); p=0.081). <i>sese</i> had a significantly reduced frequency of <i>Pseudomonas aeruginosa</i>-dominated airway infection (8.7%) compared with <i>Sese</i> (31%; p=0.042) and <i>SeSe</i> (36%; p=0.035). In contrast, fungal, viral and non-dominant bacterial components of the microbiome were not significantly different between <i>FUT2</i> genotypes. <i>FUT2</i> genotype in patients with non-cystic fibrosis bronchiectasis was significantly associated with disease outcomes, with homozygous secretors exhibiting lower lung function, higher exacerbation number and a higher frequency of <i>P. aeruginosa</i>-dominated infection. ACTRN12609000578202 (anzctr.org.au); Pre-results.