Bronchial CD8 cell infiltrate and lung function decline in asthma

Rationale: Patients with asthma have an accelerated decline in lung function, which can lead to irreversible airway obstruction. It is generally assumed that this is related to specific aspects of airway inflammation and/or remodeling. Objective: We investigated the prognostic significance of bronchial eosinophil and CD8(+) cell counts and subepithelial reticular layer thickness for the subsequent decline in lung function in patients with asthma after 7.5 years of follow-up. Methods: In a prospective study, pre- and post-bronchodilator lung function (FEV1) was measured at baseline, and after 2 years and 7.5 years in 32 patients with asthma. Annual decline in lung function after 7.5 years of follow-up was related to type and severity of airway inflammation and remodeling in bronchial biopsies, which were taken at baseline and at Year 2. Results: Annual decline in post-bronchodilator FEV1 (mean [SD], 46.6 (53.4] ml/year) was significantly larger than the decline in prebronchodilator FEV1 (mean [SD], 27.5 [62.5] ml/year), indicating loss in reversibility. Although annual fall in post-bronchodilator FEV1 was not related to thickness of the reticular layer or to eosinaphil counts in bronchial biopsies, there was a significant correlation with CD8(+) T cells (r = -0.39, p = 0.032). Analyzing the biopsies taken at Year 2, the significant association between annual fall in post-bronchodilator FEV1 and CD8 cells could independently be confirmed (r = -0.39, p = 0.036). Conclusion: The outcome of asthma, as determined by the annual decline in FEV1, can be predicted by the bronchial CD8(+) cell infiltrate. This suggests that the inflammatory phenotype in asthma has prognostic relevance, which may require phenotype-specific therapeutic strategies.