Ventilatory-perfusion relationships and respiratory drive in chronic obstructive pulmanory disease : with special reference to hypoxaemia, sleep quality and treatment with inhaled corticisteroid

By measuring retention in blood and excretion in exhaled air of six infused inert gases using multiple inert gas technique (MIGET), it is possible to obtain detailed assessment of the ventilation-perfusion (VA/Q) relationships in patients with chronic obstructive pulmonary disease.

Stable, non-bronchitic COPD patients show a substantial perfusion of hyper-ventilated lung regions. For individuals with exclusively nocturnal hypoxaemia, when the nocturnal arterial oxygen saturation (Sa02) is below 90%, an increase in dispersion of ventilation (log SW) is present together with significantly prolonged superficial sleep compared with normal. Substantial perfusion of relatively poorly ventilated lung areas (0.1A/Q<0.3) may reflect severity of nocturnal hypoxaemia. Reduced nocturnal Sa02 associates with frequent sleep stage changes when compared with healthy individuals. A significant deterioration in lung function and a prolongation of proper sleep time precede the appearance of a low resting, daytime Pa02 level of less than 7.3 kPa or 7.3-7.9 kPa in presence of severe heart failure (denoted daytime hypoxaemia), with no development of progressive nocturnal hypoxaemia. Long-term oxygen treatment (LTOT) given for six months to stable COPD patients with daytime hypoxaemia is not accompanied by an increase in shunt, or by any significant changes in the VA/Q ratios. LTOT tends to reduce minute ventilation.

Sensitivity of the central respiratory center to hypercapnea may be assessed by carbon dioxide (C02) rebreathing tests. The ventilatory response to hypercapnea (HCVR) is influenced by chest wall mechanics and level of airway resistance. Hypercapnic respiratory drive response assessed as inspiratory mouth occlusion pressure for 100 msec. (PiO.1) reflects output of the central respiratory centre and strength of the respiratory muscles. In COPD patients with daytime hypoxaemia or with exclusively nocturnal hypoxaemia, the baseline respiratory drive (before C02 rebreathing) is significantly increased compared with normal. Although HCVR is reduced, respiratory drive response remains at a normal level in such COPD patients.

Inhalations of corticosteroids for two months in stable, emphysematous COPD patients are not associated with changes in lung volumes or in ventilation-perfusion matching, but may significantly improve diffusing capacity, probably by diminishing inflammatory processes in the small airways.

High resolution computed tomography (HRCT) scanning of the lungs is an excellent method for localising and describing the extent of emphysema (which is inversely correlated with lung volumes and diffusing capacity), but is not related to either ventilation-perfusion inequality or blood gas levels.

Conclusions: The MIGET test, using peripheral venous samples, is a reliable method for prospective studies of VA/Q relationships in COPD. In stable, non-bronchitic, emphysematous COPD patients: • A significant increase in minute ventilation to sparsely perfused lung regions (high VA/Q) is present; • Substantial nocturnal hypoxaemia may persist for at least one year before daytime hypoxaemia develops; • Sleep fragmentation and high C02 sensitivity are important defence mechanisms against sleep- related hypoxaemia; • Important daytime hypoxaemia regulators are level of shunt and increase in minute ventilation to high VA/Q areas; • HCVR is an important regulator of the PaC02 level.

List of scientific papers

I. Sandek K, Andersson T, Bratel T, Lagerstrand L (1995). "Ventilation-perfusion inequality in nocturnal hypoxaemia due to chronic obstructive lung disease (COLD). " Clin Physiol 15(5): 499-513
https://pubmed.ncbi.nlm.nih.gov/8846670

II. Sandek K, Andersson T, Bratel T, Hellstrom G, Lagerstrand L (1999). "Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia. " Respir Med 93(2): 79-87
https://pubmed.ncbi.nlm.nih.gov/10464857

III. Sandek K, Bratel T, Hellstrom G, Lagerstrand L (2001). "Ventilation-perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long-term oxygen treatment (LTOT). " Clin Physiol 21(5): 584-93
https://pubmed.ncbi.nlm.nih.gov/11576160

IV. Sandek K, Bratel T, Lagerstrand L (2001). "Effects on diffusing capacity and ventilation--perfusion relationships of budesonide inhalations for 2 months in chronic obstructive pulmonary disease (COPD). " Respir Med 95(8): 676-84
https://pubmed.ncbi.nlm.nih.gov/11530957

V. Sandek K, Bratel T, Lagerstrand L, Rosell H (2002). "Relationship between lung function, ventilatio-perfusion inequality and extent of emphysema as assessed by high resolution computed tomography (HRCT)." Respiratory Medicine (Accepted)