© 2005 American Thoracic Society
Fluticasone Reduces CRP in COPDFrom the Authors:There is a marked scarcity of data regarding the systemic bioactivity of inhaled fluticasone in chronic obstructive pulmonary disease (COPD). Although interesting, Lee and Lipworth's data (1) on 2 mg per day of fluticasone in COPD are unlikely to be germane to our study, as we achieved all of the reductions in C-reactive protein (CRP) in our cohort with only 1 mg per day of fluticasone (2). Previous data from Brutsche and coworkers (3) indicate that systemic availability of fluticasone with 1 mg per day is small, particularly in patients with reduced forced expiratory volume in one second or in those with compromised diffusion capacities. For example, in patients with carbon monoxide transfer coefficients of less than 80% of predicted (which would be the case for most patients with COPD), systemic availability of fluticasone was less than 10%. Whether such small amounts of systemically absorbed fluticasone can significantly reduce CRP is open to question. We believe this to be unlikely, since the magnitude of CRP reduction observed with fluticasone (1 mg/d) was similar to that achieved by 30 mg per day of prednisone in our study (2). Nevertheless, future studies are needed to clearly delineate the exact mechanism(s) through which inhaled fluticasone and other corticosteroids exert their action on CRP and other relevant systemic proteins and cytokines in COPD. Our study was concerned with the possible systemic antiinflammatory effects of corticosteroids. We share Dr. Virchow's caution in not overinterpreting the clinical implications of our data. We agree that CRP and other markers of systemic inflammation are imperfect surrogates for future morbidity and mortality in COPD, and we cannot assume that the reductions in these levels will necessarily lead to improved clinical outcomes. However, the comparison of inhaled corticosteroids to rofecoxib is neither fair nor justified. In spite of rofecoxib's beneficial effects on CRP, there were many high-quality studies (even before the APPROVe study [4]) that had indicated their potential harm (5). Moreover, there was a sound physiologic basis for their ability to increase cardiovascular risks (6). In contrast, inhaled corticosteroids have been linked with improved cardiovascular outcomes (7) and sound experimental evidence for their potential efficacy in reducing cardiovascular events (8–10). Thus, our study data must be interpreted in the context of the entire body of evidence. The results from the TORCH trial and a meta-analysis of mortality experience in the previous placebo-controlled studies will provide definitive data on whether inhaled corticosteroids do or do not reduce mortality in COPD (11).
a University of British Columbia Vancouver, British Columbia, Canada FOOTNOTES Conflict of Interest Statement: D.D.S. received honoraria for speaking engagements from AstraZeneca in 2003 for $4,000 and in 2004 for $3,000 and from GlaxoSmithKline (GSK) in 2003 for $4,000 and in 2004 for $8,000 and has also received unrestricted research funding as either the principal investigator or co-principal investigator from GSK in 2002 for $100,000, in 2003 for $80,000, and in 2004 for $1.5 million, and has also received $3,500 from GSK for consultancy work; P.M. received $4,000 per annum from Merck Frosst Canada Inc. for Advisory Board function from 2001–2003 and $2,000 from GSK for 2003 and a medical school grant to attend the 2003 ATS meeting and has received as co-principal investigator a medical school grant from GSK, $140,000, and from Merck, $2.45 million until 2003, and a medical school grant is being negotiated and a consultation is still in progress with GSK, and was invited to speak at an AstraZeneca sponsored scientific meeting in April 2004 with all travel expenses paid by the hosting company; P.L. received $1,000 in 2004 for an invited lecture at St. Paul's Hospital Vancouver sponsored by Merck Frosst Canada and also received 30% of $60,000 for an unrestricted research grant from Abbott Laboratories in 2001–2002; E.Y. was on the GSK Medical Advisory Board from 2002 to 2003 but is no longer a member of this board (last meeting was in November 2003) and did not receive monetary payment. REFERENCES
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