Controlled short-term trial of fluticasone propionate in ventilator-dependent patients with COPD.
BACKGROUND
There is no agreement about the efficacy of systemic corticosteroids in patients with COPD, but corticosteroids often are employed during exacerbations of the disease. The use of systemic or inhaled corticosteroids in patients in stable condition is even more controversial, even though the more severely affected patients seem to respond better. Unfortunately, in this subset of patients, the use of forced expiratory maneuvers frequently fails to detect significant functional response.


OBJECTIVE
We evaluated the short-term effects of an inhaled corticosteroid, fluticasone propionate (FP), on FEV(1) and on the mechanical properties of patients in stable condition with severe COPD and chronic hypercapnic respiratory failure who were receiving long-term ventilatory support. This allowed us to measure respiratory mechanics (RM) passively, thereby avoiding any problems linked with voluntary maneuvers.


METHODS
Randomized, placebo-controlled, crossover study.


METHODS
A respiratory ICU.


METHODS
Twelve hypercapnic COPD patients (mean [+/- SD] PaCO(2), 60+/-11 mm Hg; mean FEV(1), 13+/-5% predicted; and mean FEV(1)/FVC, 31 +/- 7%) were enrolled.


METHODS
A daily dose of 2,000 microg 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.


METHODS
End-expiratory and end-inspiratory airway occlusions were performed to assess static intrinsic positive end-expiratory pressure (PEEPi,st), static compliance of the respiratory system (Cst,rs), maximal respiratory resistance (Rmax, rs), and minimal respiratory resistance (Rmin,rs). The bronchodilator response also was assessed by FEV(1) level.


RESULTS
No significant changes were found in RM after administration of the placebo. By day 6, FP had induced the following significant decreases: PEEPi,st, 4.3+/-2.4 to 3.1+/-1.7 cm H(2)O (p<0.01); Rmax,rs, 19.0+/-6.5 to 14.6+/-6 cm H(2)O/L/s (p<0.001); and Rmin,rs, 14.8+/-4.2 to 10.5+/-3.4 cm H(2)O/L/s (p<0.001). The Cst,rs and the effective additional resistance of the respiratory system did not change significantly, the latter suggesting that the major effect of FP was on the airway caliber (Rmin,rs). FEV(1) changes significantly (p<0.01) underestimated the bronchodilator response, as compared with changes in Rmin,rs.


CONCLUSIONS
We conclude that in patients in stable condition with severe COPD and chronic hypercapnic respiratory failure, a brief trial of FP may induce a bronchodilator response, mainly related to a reduction in airway resistances, that is not detected by the usual pulmonary function tests.
Nava
S
S
Respiratory Intensive Care Unit, Fondazione S. Mougeri, Istituto Scientifico di Pavia, FRCCS, Pavia, Italy. snava@fsm.it
Compagnoni
M L
ML
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001784:Blood Gas Analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids; D006801:Humans; D008170:Lung Compliance / Q000187:drug effects; D008173:Lung Diseases, Obstructive / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011175:Positive-Pressure Respiration; D016896:Treatment Outcome
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D000068298:Fluticasone