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Bronchial CD8 Cell Infiltrate and Lung Function Decline in Asthma

Departments of Pulmonology and Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands; and Department of Pathology, Sao Paulo University Medical School, Sao Paulo, Brazil

Correspondence and requests for reprints should be addressed to Prof. P. J. Sterk, M.D., Ph.D., Department of Pulmonology, C3-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: p.j.sterk{at}lumc.nl

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 eosinophil 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.

Key Words: asthma • CD8 cells • inflammation • lung function decline • prognosis

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