Abstract

Aims
 
The aim of this study is to develop a bronchoalveolar lavage (BAL) method that represents the alveoli, rather than larger airways, and addresses variable BAL return observed in COPD and alpha-1 antitrypsin deficiency (AATD).

Methods
 
Patients referred through the Irish Centre for Genetic Lung Disease were evaluated. This included healthy and emphysematous patients with severe AATD (ZZ), mild (MZ), and controls with normal levels of AAT (MM). 70 patients underwent time-matched phlebotomy and BAL. A 6th to 8th order bronchus was wedged with a paediatric bronchoscope and BAL performed with either 50, 100, or 150ml saline. BAL was performed in a smaller cohort with a traditional adult bronchoscope. BAL neutrophil count, macrophages, surfactant, secretory leukocyte protease inhibitor (SLPI), and epithelial lining fluid (ELF) were used to distinguish proximal from distal airways.

Results
 
BAL return positively correlated with FEV1 (P=<0.0001, R2=0.428). Return was significantly higher in healthy than COPD individuals (50.9% vs 30.4%, P=<0.0001), but ELF sampled was the same (0.91ml vs 0.98ml, P=0.617). ELF sampling was insufficient with 50ml BAL compared with 100 or 150ml (0.46ml vs 1.07ml vs 0.99ml, P=0.05). The paediatric bronchoscope yielded more cells (8.6x106 vs 4.9x106), sampled more ELF (1.15ml vs 0.56ml, P=0.02), fewer neutrophils (1.1% vs 4.3%, P=0.002), more macrophages (94.9% vs 86.9%, P=0.038), and less SLPI (1.3µM vs 2.1µM).

Conclusions

ELF correction is essential in COPD and BAL research due to variable return.  A paediatric bronchoscope maximises cell count and avoid excessive large airway sampling, as evidenced by greater ELF volume, fewer neutrophils, more macrophages, and less SLPI.