In smokers with chronic airflow limitation (CAL), airway hyperresponsiveness (AHR) to stimuli like methacholine, which act directly on airway smooth muscle, are not specific for the pathogenesis which is responsible for AHR to methacholine in subjects with normal spirometry, nor predictive for a beneficial effect of glucocorticosteroid (GCS) treatment. In contrast, AHR to stimuli like hyperventilation, which act indirectly through mediator release, may be specific for the pathogenesis of asthma and predictive for a beneficial effect of GCS. The validation of this possibility requires the demonstration that patients with CAL and AHR to hyper-ventilation demonstrate improvement after treatment with GCS (and have an increase in eosinophils and metachromatic cells in the sputum or bronchoalveolar lavage (BAL), like that seen in asthmatics uncomplicated by CAL).