Smoking Affects Response to Inhaled Corticosteroids or Leukotriene Receptor Antagonists in Asthma
One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. In a multicenter,...
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| Published in | American journal of respiratory and critical care medicine Vol. 175; no. 8; pp. 783 - 790 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
Am Thoracic Soc
15.04.2007
American Lung Association American Thoracic Society |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1073-449X 1535-4970 |
| DOI | 10.1164/rccm.200511-1746OC |
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| Summary: | One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.
To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.
In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.
Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.
In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Originally Published in Press as DOI: 10.1164/rccm.200511-1746OC on January 4, 2007 Supported by National Institutes of Health 5 U10 HL051810, 5 U10 HL051823, 5 U10 HL051831, 5 U10 HL051834, 5 U10 HL051843, 5 U10 HL051845, and 5 U10 HL056443. 3M, Inc., provided beclomethasone HFA inhalers and matching placebos, but had no input into the design, conduct, or interpretation of this study. Correspondence and requests for reprints should be addressed to Stephen C. Lazarus, M.D., University of California, San Francisco, 505 Parnassus Avenue, M-1083, San Francisco, CA 94143–0111. E-mail: lazma@ucsf.edu Conflict of Interest Statement: S.C.L. received $9,000 in 2003 and $3,000 in 2004 from Merck and $2,000 in 2004 from Critical Therapeutics for serving on advisory boards, $2,500 in 2004 from GlaxoSmithKline and $5,500 in 2005 from Merck for participating as a speaker in scientific programs, and $36,000 in 2003 from Abaris Pharma as a research grant for participating in a clinical trial. V.M.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.J.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.A.B. received payments in 2003 and 2004 from GlaxoSmithKline for service on a steering committee for a multicenter study, chairing and speaking at conferences, and directs a research project funded by the company at University of California, San Francisco, as well as receiving payments for honoraria and consulting from Altana, Sanofi-Aventis, Boehringer-Ingelheim, Novartis, and Sumitomo. R.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.J.C. has a pending consultancy with Schering-Plough, is an advisory board member of Sanofi-Aventis, and received $8,000 in lecture fees from Merck, $6,000 in lecture fees from Genentech, $5,000 in lecture fees from GlaxoSmithKline, and $5,000 in lecture fees from Schering-Plough; he has pending sponsored grants from Schering-Plough and Merck, and $50,000 in grants from GlaxoSmithKline, and received $100,000 grants from the American College of Allergy, Asthma, and Immunology (ACAAI), and $5,000 from Methaparm. He has received $125,000 in research grants from AstraZeneca, $325,000 in research grants from Boehringer-Ingelheim, $75,000 in research grants from Novartis, $50,000 in grants from Genentech, $85,000 in research grants from Dyax, $50,000 in research grants from Lev, $25,000 in research grants from Protein Design Labs, $25,000 in research grants from Centacore, and $200,000 in research grants from Sanofi-Aventis. A.D. has served on advisory boards for AstraZeneca in October 2002 and for Aerocrine, Inc., in May 2002; Brigham and Women's Hospital received a research grant of $55,000 for a clinical trial conducted in January 2005 with A.D. as the site investigator. E.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.E.F. was an employee of Sanofi-Aventis at the time of this study, a pharmaceutical company involved in developing an inhaled corticosteroid (ciclesonide). This inhaled corticosteroid may be viewed as a potential competitor to the study drug, beclomethasone HFA; however, ciclesonide remains an experimental drug (not approved by the Food and Drug Administration). He currently is an employee of Genentech, Inc. J.G.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.I. served as a consultant for Asthmatx in 2005 and received between $10,000 and $20,000. A multicenter clinical research project at his institution is currently pending. He receives advisory board fees of less than $10,000 from Merck, received speaker's fees from Merck between 2003 and 2005, and participated in a multicenter clinical research project with Merck in 2005. He received between $10,000 and $20,000 in speaker's fees from Genentech in 2005, serves on a Genentech advisory board, and his institution is conducting a multicenter clinical trial with Genentech. In the past 3 years, E.I. participated in multicenter clinical trials with AstraZeneca, Boehringer-Ingelheim, Centocor, GlaxoSmithKline, and Merck. He received a medical school grant from Merck for support and research for less than $50,000. J.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.K. received $6,000 in 2003 and $5,000 in 2004 for speaking at conferences sponsored by Merck, $2,000 in 2004 from GlaxoSmithKline for speaking, $8,000 in 2003, $6,000 in 2004, and $3,000 in 2005 for speaking sponsored by Genentech/Novartis, $3,000 in 2005 for speaking sponsored by Sepracor, $3,000 from AstraZeneca for consulting in 2004 and 2005, $3,000 from GlaxoSmithKline for consulting, and research grants from GlaxoSmithKline, Genentech, and Boehringer-Ingelheim. R.F.L. received speaker honoraria from GlaxoSmithKline, Merck & Co., Aventis, and AstraZeneca in the last 3 years; in 2002, this totaled $22,000 and, in 2003, $12,000; all the other yearly amounts for each company were under $10,000. He also received consultant fees from AstraZeneca, Aventis, GlaxoSmithKline, and Novartis/Genentech; in 2004, he received $11,000 from AstraZeneca while all the other amounts for all years totaled under $10,000. F.T.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.J.M. received advisory board fees of less than $10,000 per year and lecture fees of greater than $10,000 per year from lvax for 2003–2005, and received lecture fees of less than $10,000 per year from Merck for 2003–2005. G.R.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.P.P. does not own any stock in pharmaceutical or other related companies except for shares in various mutual funds, but his wife is a member of an investment club that owns less than 50 shares each of various stocks. From 2003 to 2005, S.P.P. performed the following consultative or other work, including basic research studying asthma pathogenesis under the National Institutes of Health, NHLBI, Bethesda, MD: clinical trials studying new and existing therapies for asthma treatment under the National Institutes of Health, National Heart, Lung, and Blood Institute, and its Asthma Clinical Research Network, Bethesda, MD, and the American Lung Association; pharmaceutical company clinical trials, as a member of a Wake Forest University Clinical Trials Group supported by Abaris, AstraZeneca, Altana, Boehringer-Ingelheim, Centocor, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Wyeth; consulting (usually review of scientific grant proposals, review of data concerning drugs used for the treatment of asthma, or scientific writing/editing) under the National Institutes of Health, Adelphi (Respiratory Digest, Associate Editor), American Thoracic Society (AJRCCM, Associate Editor), AstraZeneca Pharmaceuticals, Asthma Leadership Council, Discovery, Genentech, Novartis, Omnicare, RAND Corporation, Respiratory Medicine (Associate Editor), Respiratory Research (Associate Editor), and Sanofi-Aventis; and participating in physician education programs (including speakers' bureaus) sponsored by American College of Chest Physicians, American Lung Association, American Academy of Allergy, Asthma & Immunology, AstraZeneca Pharmaceuticals, Merck Pharmaceuticals, Genentech, Novartis, and Respiratory and Allergic Disease Foundation. C.A.S. received $5,000 annually for speaking at conferences sponsored by GlaxoSmithKline and AstraZeneca from 2002 to 2005, $5,000 annually (2003–2005) from GlaxoSmithKline and AstraZeneca for serving on advisory boards, and $50,000 in grant support from GlaxoSmithKline for 2002–2004. S.J.S. served as a consultant and a member of an advisory board for GlaxoSmithKline, AstraZeneca, and Aventis for the last 3 years and received approximately $6,000 per year from each company, from Merck for 2 years at $5,000 per year, and also received research funds for clinical trial performances from AstraZeneca for $90,000 for 2002–2004 and Ross Pharmaceuticals for $1,200,000 for 2003–2005. M.E.W. received less than $5,000 a year for 2003–2005 from Merck, Novartis, and GlaxoSmithKline for consultancies, advisory boards, and lecture fees. J.V.F. currently serves as a consultant to Abgenix, and served as a consultant to Sanofi-Aventis and AstraZeneca in 2004. |
| ISSN: | 1073-449X 1535-4970 |
| DOI: | 10.1164/rccm.200511-1746OC |