NHLBI funded research shows alpha-1-antitrypsin deficient (AATD) individuals with normal lung function have lower respiratory tract mild inflammation. More research is needed to assess if early anti-inflammatory therapies may prevent progression of lung disease in AATD.
Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function
Respiratory Research volume 24, Article number: 40 (2023)
Alpha-1-antitrypsin deficient (AATD) individuals are prone to develop early age of onset chronic obstructive pulmonary disease (COPD) more severe than non-genetic COPD. Here, we investigated the characteristics of lower respiratory tract of AATD individuals prior to the onset of clinically significant COPD.
Bronchoalveolar lavage was performed on 22 AATD with normal lung function and 14 healthy individuals. Cell counts and concentrations of proteases, alpha-1-antitrypsin and proinflammatory mediators were determined in the bronchoalveolar lavage fluid from study subjects. In order to determine the airway inflammation, we also analyzed immune cell components of the large airways from bronchial biopsies using immunohistochemistry in both study subjects. Finally, we made comparisons between airway inflammation and lung function rate of decline using four repeated lung function tests over one year in AATD individuals.
AATD individuals with normal lung function had 3 folds higher neutrophil counts, 2 folds increase in the proteases levels, and 2–4 folds higher levels of IL-8, IL-6, IL-1β, and leukotriene B4 in their epithelial lining fluid compared to controls. Neutrophil elastase levels showed a positive correlation with the levels of IL-8 and neutrophils in AATD epithelial lining fluid. AATD individuals also showed a negative correlation of baseline FEV1 with neutrophil count, neutrophil elastase, and cytokine levels in epithelial lining fluid (p < 0.05). In addition, we observed twofold increase in the number of lymphocytes, macrophages, neutrophils, and mast cells of AATD epithelial lining fluid as compared to controls.
Mild inflammation is present in the lower respiratory tract and airways of AATD individuals despite having normal lung function. A declining trend was also noticed in the lung function of AATD individuals which was correlated with pro-inflammatory phenotype of their lower respiratory tract. This results suggest the presence of proinflammatory phenotype in AATD lungs. Therefore, early anti-inflammatory therapies may be a potential strategy to prevent progression of lung disease in AATD individuals.