1. Twenty patients with severe chronic airflow obstruction (CAFO), four of whom were hypercapnic, had greatly reduced ventilatory responses to rebreathing CO2 under hyperoxic conditions, compared with the responses in normal subjects.
2. Mouth occlusion pressure (P0.1) responses to CO2 were also reduced in the patients compared with those of normal subjects but the reduction was less severe than in the ventilatory response.
3. in ten patients with CAFO minimum pleural pressure during tidal breathing [Ppl min. (dynamic)] at a Pco2 of 8.0 kPa was only slightly less negative than in the normal subjects (−16.2 cm water vs −23.4 cm water).
4. During rebreathing end-expiratory volume (EEV) fell progressively in the normal subjects (mean fall = 800 ml); in the patients there was a progressive rise in EEV (mean rise = 390 ml).
5. When Ppl min. (dynamic) was compared with minimum static pleural pressures at the same lung volume the patients were generating a much higher proportion of their available static pressure (47.0%) than the normal subjects (26.4%) at a Pco2 of 8.0 kPa, suggesting that despite the slightly less negative Ppl min. (dynamic), inspiratory muscle activation was greater in the patients than in normal subjects. Similar conclusions were reached from an analysis of the inspiratory work of breathing.
6. We conclude that hyperinflation, by impairing the capacity of the inspiratory muscles to lower pleural pressure, reduces the ventilatory response to CO2 and adds to the effects of abnormalities in pulmonary mechanics so that measurements of absolute pleural pressure or work of breathing underestimate inspiratory muscle activation in patients with severe CAFO.
7. Hyperinflation and severe airflow obstruction also reduce the change in P0.1 for a given degree of inspiratory muscle activation.
8. Our results suggest that, despite the impaired pressure and ventilatory response to rebreathing CO2 in the patients, their central respiratory drive was greater than that of the normal subjects.