Bloch-Salisbury · Journal of applied physiology (Bethesda, Md. : 1985) 1996 · controlled crossover physiological trial · n=4

Air hunger induced by acute increase in PCO2 adapts to chronic elevation of PCO2 in ventilated humans.

Cited 29 times in the scientific literature.

Level 3 - non-randomized controlled study

Small non-randomized controlled crossover physiological study in humans

PubMed 8872667 · doi:10.1152/jappl.1996.81.2.949 · record verified 2026-08-26

What was done

Four ventilator-dependent individuals participated in a 2-week physiological study comparing mechanical ventilation with room air (placebo) versus CO2-enriched air (chronic CO2 exposure lasting several days). Ventilation and arterial PO2 were held constant between conditions. Researchers periodically assessed the sensation of air hunger by having subjects rate respiratory discomfort during brief, acute increases in end-tidal PCO2 (PETCO2).

What was found

Average resting PETCO2 was 25 Torr during control periods and 15 Torr higher during chronic CO2 exposure. The PETCO2 level required to elicit a given air hunger rating also increased by approximately 15 Torr during the chronic CO2 condition, indicating full adaptation of the sensation. Arterial pH did not fully return to control values during chronic CO2 exposure.

Why it matters

This finding demonstrates that the sensory threshold for dyspnea/air hunger resets in response to sustained hypercapnia, explaining why patients with chronic hypercapnia do not experience continuous severe respiratory distress.

Limits

The sample size is extremely small (n = 4) and limited to ventilator-dependent subjects who had an unusually low baseline PETCO2 (25 Torr). Randomization was not specified in the abstract, and direct neural mechanisms were not measured.

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