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

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 nonasthmatic 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 (FENO) 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) mum, 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 FENO 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.