genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis.

OBJECTIVE

To assess whether () genotype affects disease severity and airway infection in patients with non-cystic fibrosis bronchiectasis.

PARTICIPANTS

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.

OUTCOME MEASURES

Presence of null polymorphisms were determined by gene sequencing and verified by endobronchial biopsy histochemical staining. Outcome measures were FEV% predicted, exacerbation frequency, and bacterial, fungal and viral components of the microbiota (measured by culture independent approaches).

RESULTS

Patients were grouped by loss-of-function genotype; categorised as non-secretors (n=27, ), heterozygous secretors (n=54, ) or homozygous secretors (n=31, ). FEV% was significantly lower in patients compared with patients (mean 61.6 (SD 20.0) vs 74.5 (18.0); p=0.023). Exacerbation frequency was significantly higher in (mean count 5.77) compared with (4.07; p=0.004) and (4.63; p=0.026) genotypes. The time until first exacerbation was significantly shorter in compared with (HR=0.571 (95% CI 0.343 to 0.950); p=0.031), with a similar trend for patients (HR=0.577 (0.311 to 1.07); p=0.081). had a significantly reduced frequency of -dominated airway infection (8.7%) compared with (31%; p=0.042) and (36%; p=0.035). In contrast, fungal, viral and non-dominant bacterial components of the microbiome were not significantly different between genotypes.

CONCLUSIONS

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 -dominated infection.

TRIAL REGISTRATION NUMBER

ACTRN12609000578202 (anzctr.org.au); Pre-results.