REGIONAL VARIABILITY OF LUNG INFLAMMATION IN CYSTIC-FIBROSIS

Chest radiography in patients with cystic fibrosis (CF) frequently sho ws more severe changes in the upper lobes. We performed bronchoalveola r lavage (BAL) on 12 clinically stable, young adult patients with CF t o determine whether inflammation varies significantly among geographic ally distinct areas of the lung. We found that absolute numbers of neu trophils were generally greater in BAL fluid from the upper lobe (25.7 +/- 7.9 x 10(5) neutrophils/ml [mean +/- SEM]) of the right lung than that obtained from the right lower lobe (6.8 +/- 2.8 x 10(5) neutroph ils/ml; p < 0.01). The mean value of unopposed neutrophil elastase act ivity in upper-lobe BAL fluid (227 +/- 91 nmol peptide hydrolyzed/ml/m in) was also significantly greater than that in lower-lobe BAL fluid ( 84 +/- 43 nmol/peptide hydrolyzed/ml/min; p < 0.01), and similar diffe rences were found for myeloperoxidase activity and DNA content. Neutro phil influx and unopposed neutrophil elastase for a given region corre lated inversely with lung function or percentage of ideal body weight, and upper-versus lower-lobe differences were more pronounced in subje cts with better preservation of lung function. Our findings suggest th at regional variation in inflammation must be considered when utilizin g BAL to study lower respiratory tract inflammation in CF or to monito r responses to therapeutic interventions that can potentially diminish lung inflammation. Our findings may also have implications for the st udy of the natural history of lung inflammation and infection in neona tes, infants, and young children with CF.