An antiinflammatory effect of salmeterol, a long-acting beta(2) agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma.

The addition of long-acting beta(2) agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 -500 microgram/d) to 12 wk of supplementary treatment with salmeterol (50 microgram twice daily) or fluticasone (100 microgram twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased "allergic" airway inflammation, but conversely with a complementary antieosinophil effect.

[1]  P. Howarth,et al.  The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma. , 1999, American journal of respiratory and critical care medicine.

[2]  M. Sears,et al.  Potential masking effects of salmeterol on airway inflammation in asthma. , 1998, American journal of respiratory and critical care medicine.

[3]  G. Town,et al.  Asthma control during long term treatment with regular inhaled salbutamol and salmeterol , 1998, Thorax.

[4]  S. Oddera,et al.  Salmeterol Enhances the Inhibitory Activity of Dexamethasone on Allergen-Induced Blood Mononuclear Cell Activation , 1998, Respiration.

[5]  D. Postma,et al.  Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. , 1997, The New England journal of medicine.

[6]  Lesley Rushton,et al.  Effect of long term treatment with salmeterol on asthma control: a double blind, randomised crossover study , 1997, BMJ.

[7]  S. Wenzel,et al.  The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma. , 1997, Chest.

[8]  L. Boulet,et al.  INFLUENCE OF SALMETEROL ON CHRONIC AND ALLERGEN-INDUCED AIRWAY INFLAMMATION IN MILD ALLERGIC ASTHMA: A PILOT STUDY , 1997 .

[9]  D. McDonald,et al.  Salmeterol reduces early- and late-phase plasma leakage and leukocyte adhesion in rat airways. , 1997, American journal of respiratory and critical care medicine.

[10]  J. Walters,et al.  Salmeterol tachyphylaxis in steroid treated asthmatic subjects. , 1996, Thorax.

[11]  J. Garrett,et al.  Risk of severe life threatening asthma and beta agonist type: an example of confounding by severity. , 1996, Thorax.

[12]  D. Cockcroft,et al.  Functional antagonism: tolerance produced by inhaled beta 2 agonists. , 1996, Thorax.

[13]  R. Wilson,et al.  Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro , 1996, British journal of pharmacology.

[14]  E. Walters,et al.  Intrasubject variability in airway inflammation in biopsies in mild to moderate stable asthma. , 1996, American journal of respiratory and critical care medicine.

[15]  E. Walters,et al.  Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. , 1995, American journal of respiratory and critical care medicine.

[16]  C. Giuntini,et al.  Present state of the controversy about regular inhaled beta-agonists in asthma. , 1995, The European respiratory journal.

[17]  T. Halstensen,et al.  Erroneous immunohistochemical application of monoclonal antibody EG2 to detect cellular activation , 1994, The Lancet.

[18]  D. Postma,et al.  Partial inhibition of the early and late asthmatic response by a single dose of salmeterol. , 1994, American journal of respiratory and critical care medicine.

[19]  C. Bolliger,et al.  Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction. , 1994, The European respiratory journal.

[20]  D. Hendrick,et al.  Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics. , 1994, American journal of respiratory and critical care medicine.

[21]  P. Ind,et al.  Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid , 1994, The Lancet.

[22]  R. Dahl,et al.  The effect of salmeterol on the early‐ and late‐phase reaction to bronchial allergen and postchallenge variation in bronchial reactivity, blood eosinophils, serum eosinophil cationic protein, and serum eosinophil protein X , 1993, Allergy.

[23]  D. Hendrick,et al.  Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response. , 1993, Thorax.

[24]  R. Townley,et al.  Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation. , 1993, International archives of allergy and immunology.

[25]  D. Postma,et al.  Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol. , 1992, The Journal of allergy and clinical immunology.

[26]  A. Zwinderman,et al.  Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. , 1992, The New England journal of medicine.

[27]  S. Durham,et al.  Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. , 1992, The American review of respiratory disease.

[28]  M. Johnson,et al.  Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea‐pig lung and skin , 1992, British journal of pharmacology.

[29]  Pierre Ernst,et al.  The Use of β-Agonists and the Risk of Death and near Death from Asthma , 1992 .

[30]  N. Choudry,et al.  A comparative study in atopic subjects with asthma of the effects of salmeterol and salbutamol on allergen-induced bronchoconstriction, increase in airway reactivity, and increase in urinary leukotriene E4 excretion. , 1992, The Journal of allergy and clinical immunology.

[31]  C. Print,et al.  Regular inhaled beta-agonist treatment in bronchial asthma , 1990, The Lancet.

[32]  S. Holgate,et al.  Protection against allergen-induced asthma by salmeterol , 1990, The Lancet.

[33]  R. Djukanović,et al.  Mucosal inflammation in asthma. , 1990, The American review of respiratory disease.

[34]  S. Holgate,et al.  The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the associated change in nonspecific bronchial responsiveness. , 1989, The American review of respiratory disease.

[35]  N. Pearce,et al.  PRESCRIBED FENOTEROL AND DEATH FROM ASTHMA IN NEW ZEALAND, 1981-83; CASE-CONTROL STUDY , 1989, The Lancet.

[36]  I. Olsson,et al.  Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein , 1984, Nature.