Abstract

Background: 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.

Methods: 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 (FEV₁) and exhaled nitric oxide (FE_NO) measured, the latter in asthmatic children only.

Results: 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) μm, 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 FEV₁<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 FEV₁ (r  =  −0.57 (95% CI −0.79 to −0.23), p = 0.002) and post-bronchodilator FEV₁ (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.

Conclusion: 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.