Optimising bronchoalveolar lavage: lessons from alpha-1 antitrypsin deficiency

Area of Science:

• Pulmonary Medicine
• Biochemistry
• Genetics

Background:

• Bronchoalveolar lavage (BAL) is crucial for assessing novel therapies in alpha-1 antitrypsin deficiency (AATD).
• High interindividual variability in BAL results complicates early-phase study endpoints.
• A standardized BAL protocol is needed to minimize dilution effects and ensure reliable biochemical endpoint comparison.

Purpose of the Study:

• To evaluate different bronchoalveolar lavage (BAL) fluid correction methods for alpha-1 antitrypsin (AAT) and anti-neutrophil elastase inhibitory capacity (ANEC) in alpha-1 antitrypsin deficiency (AATD).
• To identify a BAL protocol that minimizes interindividual variability for reliable biochemical endpoint assessment in AATD research.

Main Methods:

• Compared albumin, total protein, and epithelial lining fluid (ELF) volume (via urea) as BAL fluid correction methods.
• Utilized data from severe AATD (ZZ), moderate AATD (MZ), and non-AATD (MM) individuals, including healthy, smoker, and COPD phenotypes.
• Assessed the impact of a paediatric bronchoscope on alveolar sampling quality.

Main Results:

• Paediatric bronchoscope improved alveolar sampling compared to adult scopes.
• Total protein correction significantly minimized interindividual variability in BAL alpha-1 antitrypsin (AAT) and anti-neutrophil elastase inhibitory capacity (ANEC).
• Total protein correction demonstrated strong correlations with plasma AAT levels (r²=0.83) and high inter-lobar concordance (r²=0.76).

Conclusions:

• Total protein correction of BAL fluid provides a reliable method for assessing lung biochemical endpoints in alpha-1 antitrypsin deficiency (AATD).
• This approach capitalizes on consistent AAT levels across genotypes and the strong correlation between plasma and lung AAT.
• The optimized BAL protocol aligns lung measurements closely with systemic AAT levels, facilitating accurate therapeutic efficacy assessment.