Regional Variability of Lung Inflammation in Cystic Fibrosis

Abstract

Chest radiography in patients with cystic fibrosis (CF) frequently shows more severe changes in the upper lobes. We performed bronchoalveolar lavage (BAL) on 12 clinically stable, young adult patients with CF to determine whether inflammation varies significantly among geographically distinct areas of the lung. We found that absolute numbers of neutrophils 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) neutrophils/ml; p < 0.01). The mean value of unopposed neutrophil elastase activity in upper-lobe BAL fluid (227 +/- 91 nmol peptide hydrolyzed/ml/min) was also significantly greater than that in lower-lobe BAL fluid (84 +/- 43 nmol/peptide hydrolyzed/ml/ min; p < 0.01), and similar differences were found for myeloperoxidase activity and DNA content. Neutrophil influx and unopposed neutrophil elastase for a given region correlated inversely with lung function or percentage of ideal body weight, and upper-versus lower-lobe differences were more pronounced in subjects with better preservation of lung function. Our findings suggest that regional variation in inflammation must be considered when utilizing BAL to study lower respiratory tract inflammation in CF or to monitor responses to therapeutic interventions that can potentially diminish lung inflammation. Our findings may also have implications for the study of the natural history of lung inflammation and infection in neonates, infants, and young children with CF.

Using hyperpolarized 3He MRI to evaluate treatment efficacy in cystic fibrosis patients

“…1). Early lung disease in cystic fibrosis involves upper lobes predominantly (30,31). Thus, it is not surprising that in this patient, whose baseline disease was moderate, but who presented after a period of poor adherence to home medications, these lobes showed the most dramatic effect of therapy in HP 3 He MR imaging.…”

IL-8 Dictates Glycosaminoglycan Binding and Stability of IL-18 in Cystic Fibrosis

“…The neutrophil numbers in BALF of patients with CF is estimated at least two orders of magnitude higher than patients with chronic bronchitis during a period of exacerbation (44). This neutrophilic inflammation is partially explained by the stability of IL-8 within the CF lung.…”

Cheating by type 3 secretion system-negative Pseudomonas aeruginosa during pulmonary infection

“…In such a model of pathogenesis, we would expect the establishment of spatial heterogeneity within the lung, with regards to both inflammation and the distribution of T3SS-OFF versus T3SS-ON bacteria. Interestingly, nonhomogeneity of inflammation has long been observed in the setting of CF, as assessed both by radiologic imaging and by regional BAL of chronically infected patients (32,33). Recent studies examining explanted lungs of CF patients undergoing lung transplantation have shown that bacterial distribution within the lungs also is spatially heterogeneous (34), a pattern likewise seen for viral DNA (35).…”