Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis.

INTRODUCTION: Idiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study. METHODS: In this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared. RESULTS: We found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type. DISCUSSION: Our results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists.

Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

BACKGROUND: Bronchiectasis is the outcome of a number of different airway insults. Very few studies have characterised the aetiology and utility of a dedicated screening proforma in adult patients attending a general bronchiectasis clinic. METHODS: A prospective observational study of 189 bronchiectasis patients attending two centres in the North East of England over a two-year period was performed. RESULTS: The aetiology of bronchiectasis was identified in 107/189(57%) patients. Idiopathic bronchiectasis (IB) represented the largest subgroup (43%). Post-infection bronchiectasis (PIB) constituted the largest proportion (24%) of known causes. Mean age (SD) at diagnosis was 54(20) years with a mean age at symptom onset of 37(24) years, accounting for a diagnostic delay of 17 years. Age of symptom onset was significantly younger in patients with PIB compared to IB (p < 0.0001) and in Pseudomonas sputum positive patients (p = 0.007). Screening for APBA and total immunoglobulin deficiency identified 9 (5%) patients who then had tailored treatment. Routine screening for other aetiologies was deemed unnecessary. CONCLUSION: IB and PIB accounted for two thirds of cases of bronchiectasis in a general population. We recommend routine screening for ABPA and total immunoglobulin deficiency but not for other rarer aetiologies.

Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis.

UNLABELLED: We describe our institutional efficacy experience of azithromycin 250 mg thrice weekly in adult non-cystic fibrosis bronchiectasis. METHODS: Eligibility criteria for prophylactic azithromycin included 3 exacerbations requiring rescue antibiotics over the previous 6 months. The clinical records of 56 bronchiectasis patients on azithromycin were retrospectively reviewed. Exacerbation frequency, sputum microbiology, self-reported change in sputum volume, and spirometry results were recorded. RESULTS: Mean length of treatment was 9.1 months (7.5) and 50 patients had treatment > or = 3 months. Spirometry, pre- and post-azithromycin in 29 patients, who had 3 or more months of treatment, showed a mean increase in FEV(1) of 83 ml (0.14) (P=0.005) from 1.560 to 1.643l. There was a decrease in the exacerbation frequency from 0.81/month (SD) (0.32) pre-azithromycin to 0.41/month (0.45) (P<0.001) post-azithromycin. Clinically significant suppression of previous sputum microbial isolates was also observed. CONCLUSION: Azithromycin improves exacerbation frequency, spirometry, and sputum microbiology in bronchiectasis.