Although anti-IL-5 significantly reduced blood and sputum eosinophils, there was no effect on the immediate or late-phase reaction to inhaled antigen. Furthermore, there were no changes in AHR post allergen challenge; however, changes in AHR following the antigen challenge did not occur with placebo either. These studies indicate that although eosinophils parallel the development of the late-phase reaction to inhaled antigen, they do not appear causative of this event and may not contribute to an enhancement of AHR.
Further insight into how eosinophils participate in asthma and AHR are noted in a study by Haldar and colleagues9 in which the effects of anti-IL-5 (mepolizumab) were evaluated in patients who were refractory to large doses of inhaled ICS as indicated by persistent sputum eosinophilia. In this study, treatment with mepolizumab reduced sputum eosinophil concentrations. Despite this reduction in sputum eosinophils, there was no change in pulmonary functions or AHR. However, the diminished number of eosinophils was associated with a 50% reduction in asthma exacerbations. These studies raise the possibility that sputum eosinophils do not necessarily reflect or contribute to the intensity of AHR, but rather other factors, other cells, and/or other mediators need to be considered as the dominant, causative mechanisms in this feature of airway dysfunction in asthma.
To further address how and under what conditions either structural aspects (persistent AHR) or inflammatory components (variable AHR) modulate AHR, Kariyawasam and colleagues 9° conducted a comprehensive study that used antigen bronchoprovocation to induce an allergic inflammatory response and bronchoscopy with biopsy to assess the effects of allergic inflammation on AHR. In this study, patients were seen on five separate occasions (Fig 7). Patients had screening evaluations that included obtaining bronchoscopy with bronchial biopsies after spirometry and a methacholine measurement of PC20. An allergen challenge was then performed and followed by bronchoscopy 24 h later, as well as assessment of the effect of allergen challenge on the methacholine PC20.