Investigation of bronchiectasis in severe uncontrolled asthma.

INTRODUCTION: The presence of bronchiectasis in patients with asthma varies in different reports, while a clear aetiological relation has not been precisely established. OBJECTIVES: To investigate the presence of bronchiectasis in patients with severe uncontrolled asthma and examine whether they contribute to the severity of asthma. METHODS: Patients with severe asthma were prospectively recruited. HRCT of the chest was performed to identify and grade bronchiectasis using the 'Smith' radiology scale. Investigation of the underlying cause was carried out for patients with bronchiectasis in order to exclude aetiologies other than asthma. The Statistical Package for the Social Sciences (SPSS), version 21, was used. RESULTS: Forty patients were studied, 28 women, mean age (±SD) 57.9 years (±12.4). Mean ACT score was 14.2(±4.9). Main symptoms were: wheezing (95%), cough (92%), dysponea (92%) and sputum production (72%). Mean duration of asthma was 16.5(±11.5) years, exacerbations: 4.4(±2.7)/year. In 27 patients (67.5%) bronchiectasis was diagnosed. In nine patients (22.5%) pathogens were cultured in sputum (mainly Pseudomonas aeruginosa, Haemophilus influenzae). Patients with sputum production and pathogens in sputum cultures had a higher Smith score compared to those without expectoration and without pathogens, respectively (P = .005, P < .0001). No correlation was found between the extent of bronchiectasis and lung function. The radiological severity of bronchiectasis was correlated with the antibiotic courses/year (P = .002). CONCLUSION: Bronchiectasis is common in patients with severe asthma. Sputum production and pathogen isolation in sputum may indicate the presence of bronchiectasis which seems to contribute to the severity of asthma.

Oxidative DNA damage and somatic mutations: a link to the molecular pathogenesis of chronic inflammatory airway diseases.

BACKGROUND: Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects. METHODS: Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants. RESULTS: None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis (P = .0002), smokers without COPD (P = .0056), and healthy subjects (P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD (P = .04) and smokers without COPD (P = .008), but was not statistically different (P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD (P = .001), but was not statistically significant in smokers without COPD (P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD (P = .009). CONCLUSIONS: There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.