MedWire News: The pattern of inflammation in the airway lumen of children with cystic fibrosis (CF) differs from that in the bronchial mucosa, study data show.
"In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterized by the recruitment and accumulation of lymphocytes," report Nicolas Regamey (University Hospital of Bern, Switzerland) and colleagues in Thorax.
The researchers explain that most studies on inflammation and airway remodeling in CF have been performed on bronchoalveolar lavage (BAL) fluid. By contrast, the airway wall - the site of the destructive changes - has thus far been underinvestigated.
To see whether the pattern of inflammation in the airway lumen of children with CF reflects that in the airway wall, Regamey and team obtained BAL fluid and endobronchial biopsies from 46 children with CF and 16 disease-free controls.
They found that BAL fluid from children with CF contained significantly more inflammatory cells of every type compared with controls (overall median 1382 vs 102 cells x 103/ml), but neutrophils were the predominant cell type in the children with CF. By contrast, most of the inflammatory cells in control BAL fluid were macrophages.
Although the number of inflammatory cells was also significantly higher in subepithelial bronchial tissue from children with CF than in that from controls (median 1773 vs 1045 cells/mm2), the predominant cells in both CF and control samples were T-lymphocytes, followed by macrophages, with few neutrophils, eosinophils, or mast cells present in either.
The higher numbers of lymphocytes in the bronchial mucosa of children with CF compared with controls clearly indicates that the presence of these cells is not just a feature of end-stage disease but part of the ongoing inflammatory process of CF, the researchers remark.
They add: "The pathophysiological function of these infiltrating lymphocytes is unclear, but it could be speculated that T-lymphocytes… may be involved in disease progression - for instance, through the induction of matrix metalloproteinase expression, known to be present in BAL fluid of subjects with CF and believed to be involved in airway tissue destruction."
When the researchers looked at samples collected during chest exacerbations, they found that BAL fluid from children with CF had more inflammatory cells of all types compared with those with stable disease. However, in biopsies only the numbers of lymphocytes and macrophages, but not of neutrophils, were higher.
In addition, children with a positive culture of Pseudomonas aeruginosa had significantly higher numbers of T lymphocytes in subepithelial bronchial tissue than did children negative for this pathogen (median 1174 vs 714 cells/mm2), but no changes were seen in BAL fluid.
Statistical analysis showed that cell counts in both BAL fluid and biopsy specimens correlated with age, but were unrelated to each other.
"These data demonstrate that BAL fluid and endobronchial biopsy provide different but complementary information, and both need to be sampled in order to be able to understand fully the pathophysiological processes in CF," Regamey and co-authors conclude.
They add: "Considering that progressive airway wall changes ultimately lead to bronchiectasis, we suggest that further research should focus on understanding the pathogenetic mechanisms at this tissue site.".
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
Free abstract
