Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms.

Abstract

The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.