Potential masking effects of salmeterol on airway inflammation in asthma.
We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.
Mcivor
R A
RA
Firestone Regional Chest and Allergy Unit, St. Joseph's Hospital-McMaster University, Hamilton, Ontario, Canada.
Pizzichini
E
E
Turner
M O
MO
Hussack
P
P
Hargreave
F E
FE
Sears
M R
MR
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000503:physiopathology*; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use; D018592:Cross-Over Studies; D018450:Disease Progression; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D010919:Placebos; D012260:Ribonucleases; D000068299:Salmeterol Xinafoate; D013147:Spirometry; D013183:Sputum / Q000166:cytology
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D001798:Blood Proteins; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D018836:Inflammation Mediators; D010919:Placebos; D016210:Methacholine Chloride; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D012260:Ribonucleases; D001507:Beclomethasone; D000420:Albuterol