Controlled short-term trial of fluticasone propionate in ventilator-dependent patients with COPD

Background: There is no agreement about the efficacy of systemic corticoste roids in patients with COPD, but corticosteroids often are employed during exacerbations of the disease. The use of systemic or inhaled corticosteroid s in patients in stable condition is even more controversial, even though t he more severely affected patients seem to respond better. Unfortunately, i n this subset of patients, the use of forced expiratory maneuvers frequentl y fails to detect significant functional response. Study objectives: We evaluated the short-term effects of an inhaled cortico steroid, fluticasone propionate (FP), on FEV1 and on the mechanical propert ies of patients in stable condition with severe COPD and chronic hypercapni c respiratory failure who were receiving long-term ventilatory support. Thi s allowed us to measure respiratory mechanics (RM) passively, thereby avoid ing any problems linked with voluntary maneuvers. Design: Randomized, placebo-controlled, crossover study. Setting: A respiratory ICU. Patients: Twelve hypercapnic CORD patients (mean [+/- SD] Paco(2), 60 +/- 1 1 mm Hg mean FEV1, 13 +/- 5% predicted; and mean FEV1/FVC, 31 +/- 7%) were enrolled. Interventions: A daily dose of 2,000 mug FP or placebo was administered via metered-dose inhaler during mechanical ventilation for 5 consecutive days, A washout of 72 h was allowed between regimens. Measurements: End-expiratory and end-inspiratory airway occlusions were per formed to assess static intrinsic positive end-expiratory pressure (PEEPi,s t), static compliance of the respiratory system (Cst,rs), maximal respirato ry resistance (Rmax,rs), and minimal respiratory resistance (Rmin,rs). The bronchodilator response also was assessed by FEV1 level. Results: No significant changes mere found in RM after administration of th e placebo. By day 6, FP had induced the following significant decreases: PE EPi,st, 4.3 +/- 2.4 to 3.1 +/- 1.7 cm H2O (p < 0.01); Rmax,rs, 19.0 +/- 6.5 to 14.6 +/- 6 cm H2O/Ls (p < 0.001); and Rmin,rs, 14.8 +/- 4.2 to 10.5 +/- 3.4 cm H2O/L/s (p < 0.001), The Cst,rs and the effective additional resist ance of the respiratory system did not change significantly, the latter sug gesting that the major effect of FP was on the airway caliber (Rmin,rs). FE V1 changes significantly (p < 0.01) underestimated the bronchodilator respo nse, as compared with changes in Rmin,rs. Conclusions: We conclude that in patients in stable condition with severe C OPD and chronic hypercapnic respiratory failure, a brief trial of FP may in duce a bronchodilator response, mainly related to a reduction in airway res istances, that is not detected by the usual pulmonary function tests.