Airway hyperresponsiveness in a large group of subjects with α₁-antitrypsin deficiency: A cross-sectional controlled study

Background. It has been suggested that subjects with α₁-antitrypsin (AAT) deficiency, lacking a major antiprotease defence against airway inflammation, might be more susceptible of development of airway hyperresponsiveness (AHR). Moreover, lower AAT blood levels might also be able to influence the severity of AHR. Objectives. This study was aimed to investigate the prevalence of AHR in a large group of subjects with AAT deficiency included in the Italian Registry and to evaluate the relationship between AAT blood levels and the severity of AHR in this population. Design. Cross-sectional controlled study. Setting. Regional Reference Centre for AAT deficiency in Brescia, Italy. Methods. A total of 114 subjects with AAT deficiency underwent pulmonary function tests. Eighty-six were eligible to perform a bronchial provocation test with methacholine (MCh) (baseline FEV₁ > 60% predicted) to assess the provocative dose producing a 20% fall of FEV₁ (PD₂₀FEV₁). Similar measurements were performed in a control group of 27 age-matched normal subjects. Results. The prevalence of AHR (PD₂₀FEV₁ < 2000 μg MCh) was not different between AAT deficiency subjects and controls (16.3% and 11.1%, respectively; P = 0.66), and also amongst two subgroups of AAT deficiency subjects divided according to different protease inhibitor (Pi) phenotypes (PiMZ-MS, PiSZ-ZZ). Hyperresponsive subjects with AAT deficiency, however, showed a positive correlation between AAT blood levels and PD₂₀FEV₁ values (r = 0.71, P < 0.01). Conclusions. These findings indicate that AAT deficiency subjects did not exhibit a greater prevalence of airway hyperresponsiveness as compared with control subjects, but suggest that, in the subset of AAT deficiency subjects hyperresponsive to MCh, lower levels of AAT are associated with a higher severity of AHR.