The presence of emphysema does not affect the systemic bioactivity of inhaled fluticasone in severe chronic obstructive pulmonary disease.
OBJECTIVE
To assess the systemic bioactivity of fluticasone proprionate (FP) 2000 micro g daily on sensitive adrenal and bone markers in severe chronic obstructive pulmonary disease (COPD) patients with or without significant emphysema.


METHODS
Ten patients without emphysema (COPD group: age 55 years, FEV(1) 51% predicted and DL(CO) 83% predicted) and 10 patients with emphysema (COPDE group: age 59 years, FEV(1) 43% predicted and DL(CO) 49% predicted) received FP 2000 micro g daily via a spacer for 2 weeks. There was a 1-week washout period prior to FP treatment where patients were given salmeterol and oxitropium, after stopping their usual inhaled corticosteroids for the duration of the study. Measurements including overnight 10 h urinary cortisol excretion corrected for creatinine (OUCC) and serum osteocalcin concentrations were performed at baseline following washout and after 2 weeks of FP.


RESULTS
Values for OUCC and serum osteocalcin concentrations pre- and post-FP were not significantly different between the COPD and COPDE groups. There was significant suppression of OUCC (nmol mmol(-1)) by FP treatment within the COPD group (P = 0.03): 7.86 vs 4.64 (95% CI on the difference 0.47, 5.98), and within the COPDE group (P = 0.006): 7.13 vs 4.27 (95% CI on the difference: 1.03, 4.69). Likewise, there was significant suppression of osteocalcin concentration (nmol l(-1)) by FP treatment within the COPD group (P = 0.04): 7.24 vs 6.34 (95% CI on the difference: 0.01, 1.78), and within the COPDE group (P = 0.03): 6.92 vs 5.72 (95% CI on the difference: 0.12, 2.29).


CONCLUSIONS
Severe COPD patients who are receiving high dose FP are susceptible to the development of systemic adverse effects, irrespective of the presence of emphysema.
Lee
Daniel K C
DK
Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom.
Lipworth
Brian J
BJ
D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000097:blood / Q000150:complications* / Q000503:physiopathology
D000730:Androstadienes; D001993:Bronchodilator Agents; D015675:Osteocalcin; D000068298:Fluticasone; D006854:Hydrocortisone