The main findings of the study are the following. No functional parameter either at rest or during exercise was significantly different and able to distinguish in a population of subjects with mild persistent asthma who would have had EIBa and who not. In contrast with asthmatics without EIBa, however, in those with EIBa, IC did not increase during exercise, and some of them (in our series 50%) developed DH during exercise with earlier FEV1 fall after stopping it. This subgroup of asthmatics with EIBa with DH during exercise (subgroup 2) showed a significant reduction of FEF25-75% at rest and higher airway responsiveness to methacholine, suggesting a more extensive structural and functional involvement of small airways.
We did not found any respiratory functional parameters at rest useful to predict the occurrence of exercise-induced bronchoconstriction in relatively young asthmatics with similar history and severity of disease (mild persistent asthma). Also during exercise, albeit patients developing EIBa had slightly lower mean peak values of workload and oxygen uptake, there were no significant differences in average between the two groups.
Asthmatics with EIBa, however, showed a distinct functional behavior during exercise characterized by the absence of EELV reduction (Fig. 1) with a subgroup developing DH, as witnessed by the progressive IC decrease, that was associated with significantly reduced forced expiratory flows at lower lung volumes at baseline and higher airway responsiveness.
In the presence of normal FEV1 and FVC, reduced FEF25-75% strongly suggests an increased up-stream resistance in these asthmatics’ small airways that, favoring a larger ventilation heterogeneity, may in part explain the higher airway hyperresponsiveness we observed concurrently (14).
The baseline reduced expiratory flow reserve at lower lung volumes, corresponding to the tidal volume range, may promote tidal expiratory flow limitation (EFL) when the ventilatory requirements increase during exertion. This possibility was elegantly demonstrated by Kosmas and coworkers some years ago, using the negative expiratory pressure technique, in a large percentage of subjects suffering from asthma of different severity, from intermittent or mild to severe, but without EIBa, during symptom-limited incremental bicycle exercise test (15). Also in this study, asthmatics who developed EFL during exercise had a lower baseline FEF25-75% and FEF75% than those without EFL during exercise.
An increment of airway resistance throughout the exercise observed in some asthmatics (15,16), especially with EIBa (9, 17,18), can markedly increase this possibility.
In these circumstances breathing at higher operative lung volumes allows to escape tidal EFL or have minimal EFL and continue exercising but at the expense of progressive DH (19).
Therefore, these indices such as FEF25-75% and PD20FEV1, easily obtained at rest, could explain why some asthmatics with EIBa may have symptoms also during effort linked to the development of DH that might limit their exercise tolerance and maximal performance because of its associated mechanical constraints.
In the future would be interesting by using FOT to measure parameters of respiratory system resistance (Rrs5-Rrs20 difference) and reactance (Xrs5 or AX), exploring small and peripheral airway mechanical properties to confirm this hypothesis in asthmatics suffering from EIBa, who begin to have symptoms also during effort (20).
Higher airway hyperresponsiveness (i.e., higher sensitivity as PD20FEV1) can ensue from a deeper epithelial damage associated with either greater airway inflammation or abnormal neurogenic control or both, and this condition may certainly induce a worse functional impairment of small airways. Concurrently, larger ventilation heterogeneity sustained by a marked small airway involvement might also explain a higher airway hyperresponsiveness (13). We cannot discriminate between these two different mechanisms that, however, could coexist in this subgroup of asthmatics with EIBa.
This study is limited by the relatively small number of subjects and possibly the choice of the exercise challenge that is less than optimal for induction of EIBa, but needful to measure the operational lung volumes dynamic changes. However, we were able to elicit EIBa in more than 65% of the subjects recruited for suspicious symptoms. Finally, we do not think that the absence of a matched control group could invalidate the meaning of our findings.