The respiratory neuromuscular response to hypoxia, hypercapnia, and obstruction to airflow in asthma.

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.