The effects of the administration of 100% oxygen on minute ventilation (VE) and arterial blood gases were studied in patients with chronic obstructive pulmonary disease during acute respiratory failure. The administration of O2 resulted in an early decrease in VE, which averaged 18% +/- 2 SE of the control VE, and was due to a decrease in both tidal volume (VT) and respiratory frequency (f). This was followed by a slow increase in VE, such that after 15 min of breathing O2, VE rose to 93 +/- 6% of the control room air value, with both VT and f similar to control values. Despite the small difference between VE while breathing room air and that at the fifteenth minute of O2 inhalation, PaCO2 increased by 23 +/- 5 mmHg, and no significant correlation was found between the changes in VE and PaCO2. By the fifteenth minute of O2 inhalation the PaO2 averaged 225 +/- 23 mmHg, and it was concluded that despite the removal of the hypoxic stimulus of O2 inhalation, the activity of the respiratory muscles remained great enough to maintain VE at nearly the same degree as that while breathing room air. Consequently, the changes in PaCO2 after the administration of O2 were mainly due to increased inhomogeneity of VA/Q distribution within the lungs.

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.

To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance.