Lung inflammation occurs in patients with alpha-1 antitrypsin deficiency (AATD) prior to significant lung damage, but can be ameliorated by the early initiation of anti-inflammatory therapies, according to a study published in Respiratory Research.
Many causes of lung disease have been conclusively established, such as cigarette smoking, dust exposure, and infections. Chronic inflammation is a common feature of lung damage. Studies including individuals with AATD and chronic obstructive pulmonary disease (COPD) found proinflammatory mediators in their sputum and bronchoalveolar lavage fluid (BALF).
“Therefore, it is reasonable to believe that the intensity of inflammation correlates with the proteolytic environment and inflammatory mediators’ burden in AATD lungs,” the authors of the study wrote.
The authors hypothesized that early anti-inflammatory therapies may limit lung damage in patients with AATD. They recruited patients with AATD at the NIH Clinical Center, Bethesda, Maryland. All participants were free of respiratory tract infection at the start of the study. The research team carried out lung function tests every 3 months for 1 year. BALF samples and bronchial biopsies were likewise collected 4 times a year.
Read more about AATD etiology
The research team recruited 22 individuals with AATD, with 8 of them being ex-smokers. None were on AAT replacement therapy. A total of 14 healthy nonsmoking individuals were recruited as controls.
The researchers found that patients with AATD had signs of inflammation prior to the onset of symptomatic lung damage. They also determined that proteases had a positive correlation with interleukin-8 and neutrophils in the epithelial lining fluid of patients with AATD.
In addition, there was a negative correlation between baseline lung function performance and neutrophil counts, neutrophil elastase, and cytokine levels in the epithelial lining fluid of participants.
“We demonstrate that normal environmental exposures might not only lead to a consistent airway inflammation, but also lead to continued infiltration of inflammatory cells within the AATD airways prior to the clinical evidence of lung disease,” the authors of the study concluded.
Kokturk N, Khodayari N, Lascano J, Riley EL, Brantly ML. Lung inflammation in alpha-1-antitrypsin deficient individuals with normal lung function. Respir Res. 2023;24(1):40. doi:10.1186/s12931-023-02343-3