Association between α₁-antitrypsin and bronchiectasis in patients with humoral immunodeficiency receiving...

In patients with humoral immunodeficiency, the progression of bronchiectasis has been known to occur despite adequate gammaglobulin therapy and in the absence of recurrent infections. This observation suggests that factors other than gammaglobulin replacement might play a part in the prevention of lung damage in this population. α₁-Antitrypsin deficiency can be associated with bronchiectasis, a chronic inflammatory lung disease. The protective levels of α₁-antitrypsin and phenotype in preventing bronchiectasis have not been thoroughly studied in the immunodeficient population. We hypothesized that patients with humoral immunodeficiencies on gammaglobulin infusions and bronchiectasis have lower median levels, but not necessary "classically" deficient levels, of α₁-antitrypsin compared with those without bronchiectasis.

To compare levels of α₁-antitrypsin in subjects with immunodeficiency with and without bronchiectasis.

One hundred ninety-two subjects with humoral immunodeficiencies requiring gammaglobulin therapy had their α₁-antitrypsin levels and phenotype screened. High-resolution computed tomograms of the chest of participants were obtained and compared with α₁-antitrypsin levels and phenotype.

Participants without bronchiectasis were found to have higher median levels of α₁-antitrypsin than those with bronchiectasis (P = .003). Furthermore, subjects with improving or resolved bronchiectasis since initiating gammaglobulin therapy had higher median levels of α₁-antitrypsin than those with worsening bronchiectasis (P = .004). The prevalence of the α₁-antitrypsin PiZZ mutation was higher than in the general public (P < .0001).

Median α₁-antitrypsin levels and phenotype in subjects were associated with humoral immunodeficiency and their bronchiectasis status. Prospective studies might be necessary to determine possible benefits of augmentation therapy. This study supports the idea that what is considered a "normal or protective" α₁-antitrypsin range might need to be refined for patients with humoral immunodeficiency on gammaglobulin therapy.