Patients with Chronic Obstructive Pulmonary Disease (C.O.P.D.) may develop hypercapnia as the severity of the disease progresses. The mechanisms that lead to chronic hypercapnia are not completely understood. Although carbon dioxide retention is dependent on the severity of airway obstruction, there is considerable variability in the relationship between CO2 retention and forced expiratory volume in one second (FEV1). Others factors such as ventilation-perfusion mismatch, abnormalities in ventilatory control, respiratory muscle weakness, the pattern of breathing, and pulmonary hyperinflation have been reported to contribute to carbon dioxide retention. This study was designed to evaluate the role of the respiratory muscles in the pathophysiology of chronic hypercapnia in clinically stable C.O.P.D. patients. In order to do this, we studied ventilatory drive, respiratory pattern, gas exchange, and respiratory muscle strength in 27 normocapnic and 23 hypercapnic C.O.P.D. patients. The results were compared with 17 controls, without cardiorespiratory disease. Lung volumes were determined by whole body plethysmography. Thoracic Gas Volume (TGV) was used as the best available measure of Functional Residual Capacity (FRC). Airway obstruction was evaluated by forced airway flows and specific airway conductance (SGaw). The ventilatory drive was assessed by determination of occlusion pressure (P0.1), minute ventilation (V'E) at rest and the response to hypercapnia using Read rebreathing technique. The determination of inspiratory time (Ti), total time of the respiratory cycle (Ttot), tidal volume (VT) and the ratio VD/VT evaluated respiratory pattern. Gas exchange was assessed by determination of carbon monoxide transfer factor (TI/VA) and arterial blood gas analyses. Respiratory muscle strength was evaluated both by volitional and non-volitional methods. We used the static mouth pressures and the sniff nasal inspiratory test with measurement of pressures at nose, gastric and esophageal levels as volitional tests. The non-volitional test used was magnetic stimulation of phrenic nerves. Hypercapnic patients were more obstructed and more hyperinflated than normocapnic patients, and developed lower respiratory muscles pressures, both with volitional and non-volitional tests. However both groups of patients had higher resting P0.1 values than controls, but similar responses of this variable with CO2 stimulation. As the pressures developed by inspiratory muscles are dependent on the degree of hyperinflation, we matched two subgroups of normocapnic and hypercapnic patients (n=15) with similar levels of hyperinflation, in order to compare both groups, excluding the influence of hyperinflation. Comparing those sub-groups of patients we found that they had a similar ventilatory drive and respiratory pattern but different diffusion capacity to CO, and different diaphragmatic pressures elicited by cervical magnetic stimulation of the phrenic roots, showing the hypercapnic patients lower values. Pearson's test was used to assess the relationship between static lung function, ventilatory drive and respiratory muscle function with resting PaCO2. A stepwise multiple regression analyses determined, as best predictors of resting CO2 level, the airways obstruction (FEV1) and the reserve of pressure potentially available for inspiration (P0.1/PImax). This study has shown that irrespective of CO2 level, baseline central drive was increased in C.O.P.D. patients, and that neural inspiratory drive was well preserved in hypercapnic patients. These patients had a decreased capacity of the diaphragm to generate pressures elicited by magnetic stimulation compared with normocapnic patients, suggesting that this could be the promoter factor leading to chronic hypercapnia.
|Number of pages||73|
|Journal||Revista Portuguesa de Pneumologia|
|Publication status||Published - 2001|