Long-acting β-2-agonists: Comparative pharmacology and clinical outcomes

American Journal of Respiratory Medicine

Volumn 1, Issue 1, 2002, Pages 55-74

  van der Woude, Hanneke J ^a   Aalbers, René ^a  

^a MARTINI HOSPITAL   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BECLOMETASONE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BUDESONIDE; CORTICOSTEROID; FENOTEROL; FLUTICASONE PROPIONATE; FORMOTEROL; FORMOTEROL FUMARATE; GLUCOSE; LONG ACTING DRUG; MONTELUKAST; PLACEBO; POTASSIUM; SALBUTAMOL; SALMETEROL; SALMETEROL XINAFOATE; TERBUTALINE; ANTIINFLAMMATORY AGENT; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; DRUG DERIVATIVE; ETHANOLAMINE DERIVATIVE;

ANTIINFLAMMATORY ACTIVITY; ASTHMA; BRONCHODILATATION; BRONCHUS HYPERREACTIVITY; CARDIOVASCULAR EFFECT; CHRONOTROPISM; DIASTOLIC BLOOD PRESSURE; DISEASE EXACERBATION; DRUG ACTIVITY; DRUG DELIVERY SYSTEM; DRUG MEGADOSE; DRUG POTENCY; DRUG TOLERANCE; DYSPNEA; GLUCOSE BLOOD LEVEL; GROWTH RETARDATION; HEART RATE; HEART SUPRAVENTRICULAR ARRHYTHMIA; HOSPITAL ADMISSION; HUMAN; HYPOTENSION; IN VITRO STUDY; IN VIVO STUDY; INOTROPISM; MONOTHERAPY; NONHUMAN; POTASSIUM BLOOD LEVEL; PRIORITY JOURNAL; QT INTERVAL; REVIEW; SIDE EFFECT; SUPRAVENTRICULAR PREMATURE BEAT; TREATMENT OUTCOME; TREMOR; DOSE RESPONSE; DRUG EFFECT; MAST CELL; NEBULIZER;

ADRENERGIC BETA-AGONISTS; ALBUTEROL; ANTI-INFLAMMATORY AGENTS; ASTHMA; BRONCHIAL HYPERREACTIVITY; DOSE-RESPONSE RELATIONSHIP, DRUG; ETHANOLAMINES; HUMANS; MAST CELLS; NEBULIZERS AND VAPORIZERS;

EID: 0041385624     PISSN: 11756365     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF03257163     Document Type: Review

References (269)

1. American Thoracic Society. Standards for the diagnosis and care of patients with COPD and asthma. Am Rev Respir Dis 1987; 136: 225-44
2. Global Initiative for Asthma. Global strategy for asthma management and prevention. Washington, DC: National Heart, Lung, and Blood Institute, 1995. Publication no. 95-3659
3. The British Guidelines on Asthma Management. 1995 Review and Position Statement. Thorax 1997; 52 Suppl. 1: S1-S21
4. Jeppsson AB, Löfdahl C-G, Waldeck B, et al. On the predictive value of in vitro experiments in the evaluation of the effect duration of bronchodilator drugs for local administration. Pulm Pharmacol 1989; 2: 81-5
5. Anderson GP, Lindén A, Rabe KF. Why are long acting β-adrenoreceptor agonists long acting? Eur Respir J 1994; 7: 569-78
6. Löfdahl C. Basic Pharmacology of new long-acting sympaticomimetics. Lung 1990; 168: 18-21
7. Anderson GP. Long acting inhaled beta-adrenoceptor agonists the comparative pharmacology of formoterol and salmeterol. Agent Actions Suppl 1993; 43: 253-69
8. Roux FJ, Grandordy B, Douglas JS, et al. Functional and binding characteristics of long-acting b2-agonists in lung and heart. Am J Respir Crit Care Med 1996; 153: 1489-95
9. Naline E, Zhang Y, Qian Y, et al. Relaxant effects and durations of action of formoterol and salmeterol in the isolated human bronchus. Eur Respir J 1994; 7: 914-20
10. 2 adrenoceptor agonist with higher efficacy of guinea-pig trachea and human bronchus in vitro. Br J Pharmacol 1994; 113: 687-92
11. Molimard M, Naline E, Zhang Y, et al. Long-and short acting β2 adrenoceptor agonists: interactions in human contracted bronchi. Eur Respir J 1998; 11 583-8
12. Lindén A, Bergendal A, Ullman A, et al. Salmeterol, formoterol and salbutamol in the isolated guinea pig trachea: differences in maximum relaxant effect and potency but not in functional antagonism. Thorax 1993; 48: 547-53
13. Benovic JL, Staniszewski C, Mayor Jr F, et al. Beta-adrenergic receptor kinase. Activity of partial agonists for stimulation of adenylate cyclase correlates with ability to promote receptor phosphorylation. J Biol Chem 1988; 263: 3893-7
14. January B, Seibold A, Whaley B, et al. β2-adrenergic receptor desensitization, internalization and phosphorylation in response to full and partial agonists. J Biol Chem 1997; 272: 23871-9
15. Decker N, Quennedey MC, Rouot B, et al. Effects of N-Aralkyl substitution of β-agonists on alpha and β-adrenoceptor subtypes: pharmacological studies and binding assays. J Pharm Pharmacol 1982; 34: 107-12
16. Johnson M. The preclinical pharmacology of salmeterol: bronchodilator effects. Eur Respir Rev 1991; 1: 253-6
17. Bergendal A, Lindén A, Lötvall J, et al. Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in ferret trachea. Br J Pharmacol 1995; 14: 1478-82
18. Nials AT, Coleman RA, Johnson M, et al. The duration of action of non-β2 adrenoceptor mediated responses to salmeterol. Br J Pharmacol 1997; 120 (5): 961-7
19. Ullman A, Svedmyr N. Salmeterol, a new long acting inhaled β2 agonist: comparison with salbutamol in adult asthmatic patients. Thorax 1988; 43: 674-8
20. Bronsky EA, Kemp JP, Orgel HA, et al. A 1-week dose ranging study of inhaled salmeterol in patients with asthma. Chest 1994; 105: 1032-7
21. Green SA, Spasoff AP, Coleman RA, et al. Sustained activation of a G-protein-coupled receptor via 'anchored' agonist binding: molecular localization of the salmeterol exocite within the β2-adrenergic receptor. J Biol Chem 1996; 271: 24029-35
22. Palmer JBD, Stuart AM, Shepherd GL, et al. Inhaled salmeterol in the treatment of patients with moderate to severe reversible obstructive airway disease: a 3-month comparison of the efficacy and safety of twice daily salmeterol (100 μg) with salmeterol (50μg). Respir Med 1992; 86: 409-17
23. Dahl R, Earnshaw JS, Palmer JBD. Salmeterol: a four week study of a long acting β2-adrenoceptor agonist for the treatment of reversible airways disease. Eur Respir J 1991; 4: 1178-84
24. Fitzpatric MF, Mackay T, Driver H, et al. Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled β2 agonist. BMJ 1990; 301: 1365-8
25. Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroids with doubling the dose of inhaled steroids. Am Rev Respir Dis 1996; 153: 1481-8
26. Seberová E, Anderson A. Oxis® (formoterol given by Turbuhaler®) showed as rapid an onset of action as salbutamol given by a pMDI. Respir Med 2000; 94: 607-11
27. Wallin A, Sandström T, Rosenhall L, et al. Time course and duration of bronchodilation with formoterol dry powder inpatients with stable asthma. Thorax 1993; 48: 611-4
28. Derom EY, Pauwels RA. Time course of bronchodilating effect of inhaled formoterol, a potent and long-acting sympaticomimetic. Thorax 1992; 47: 30-3
29. Ringdal N, Derom E, Wåhlin-Boll E, et al. Onset and duration of action of single doses of formoterol inhaled via Turbuhaler. Respir Med 1998; 92: 1017-21
30. Wegener T, Hedenström H, Melander B. Rapid onset of inhaled formoterol in asthmatic patients. Chest 1992; 102: 535-8
31. Löfdahl CG, Chung KF. Long acting β2 adrenoceptor agonists: a new perspective in the treatment of asthma. Eur Respir J 1991; 4: 218-26
32. 2 adrenoceptor agonist. Acute studies of selectivity and duration of effect after inhaled and oral administration. Allergy 1989; 44: 264-71
33. Van den Berg BT, Smeets JJ, Van Boxtel CJ, et al. Evaluation of different doses of formoterol from a newly developed powder inhalation device in asthmatic patients. Fundam Clin Pharmacol 1995; 9: 593-603
34. Schreurs AJ, Sinninghe Damsté HE, De Graaff CS, et al. A dose-response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients. Eur Respir J 1996; 9: 1678-83
35. Graff-Lonnevig V. Twelve hours' bronchodilating effect of inhaled formoterol in children with asthma: a double blind, cross-over study versus salbutamol. Clin Exp Allergy 1990; 20: 429-32
36. Maesen FPV, Smeets JJ, Gubbelmans HL, et al. Bronchodilator effect of inhaled formoterol vs salbutamol over 12 hours. Chest 1990; 97: 590-4
37. Palmqvist M, Persson G, Lazer L, et al. Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency. Eur Respir J 1997; 10: 2484-9
38. Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered dose inhaler pMDI. Eur Respir J 1994; 7: 1839-44
39. Borgstörm L, Derom E, Ståuhl E, et al. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med 1996; 153: 1636-40
40. Wolfe J, Kreitzer S, Chervinsky P, et al. Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma. Ann Allergy Asthma Immunol 2000; 84: 334-40
41. Lötvall J, Mellén A, Arvidsson P, et al. Similar bronchodilation with formoterol delivered by Aeroliser or Turbuhaler. Can Respir J 1999; 6: 412-6
42. Ullman A, Löfdahl C-G, Melander B, et al. Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose-response study. Allergy 1996; 51: 745-8
43. Ramsdale EH, Otis J, Klein P, et al. The effect of long-acting β2 adrenoceptor agonist, formoterol, on methacholine airway responsiveness in asthmatic subjects. Am Rev Respir Dis 1991; 143: 998-1001
44. Derom EY, Pauwels RA, Van der Straeten MEF. The effect of inhaled salmeterol on methacholine responsiveness in subjects with asthma up to 12 hours. J Allergy Clin Immunol 1992; 89: 811-5
45. Rabe KF, Jörres R, Nowak D, et al. Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993; 147: 1436-41
46. Palmqvist M, Ibsen T, Mellén A, et al. Comparison of the relative efficacy of formoterol and salmeterol in asthmatic patients. Am J Respir Crit Care Med 1999; 160: 244-9
47. Van der Woude HJ, Winter T, Aalbers R. Decreased bronchodilating potency of salbutamol in relieving methacholin induced severe bronchoconstriction during treatment with long-acting β2-agonists. Thorax. In press
48. Barnes PJ. β-adrenergic receptors and their regulation. Am J Respir Crit Care Med 1995; 152: 838-60
49. Bhagat R, Kalra S, Swystun VA, et al. Rapid onset of tolerance to the bronchoprotective effect of salmeterol. Chest 1996; 108: 1235-9
50. Drotar DE, Davis EE, Cockroft DW. Tolerance to the bronchoprotective effect of salmeterol 12 hours after starting twice daily treatment. Ann Allergy Asthma Immunol 1998; 80: 31-4
51. Cheung D, Timmers MC, Zwinderman AH, et al. Long term effects of a long-acting β2 adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma. N Engl J Med 1992; 327: 1198-203
52. Kemp JP, DeGraff AC, Pearlman DS, et al. A 1-year study of salmeterol powder on pulmonary function and hyperresponsivenss to methacholine. J Allergy Clin Immunol 1999; 104: 1189-97
53. Rosenthal RR, Busse WW, Kemp JP, et al. Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness. Chest 1999; 116: 595-602
54. FitzGerald JM, Chapman KR, Delle Cioppa G, et al. Sustained bronchoprotection, bronchodilation and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 study Group. J Allergy Clin Immunol 1999; 103 (3 Pt 1): 427-35
55. 2 agonist salmeterol in mild to moderate asthmatic patients. Thorax 1993; 48: 1121-4
56. Fuglsang G, Vikre-Jørgensen J, Angertoft L, et al. Effect of salmeterol treatment on nitric oxide level in exhaled air and dose-response to terbutaline in children with mild asthma. Pediatr Pulmonol 1998; 25: 314-21
57. Grove A, Lipworth B. Bronchodilator subsensitivity to salbutamol after twice daily salmeterol in asthmatic patients. Lancet 1995; 346: 201-6
58. Tan KS, Grove A. McLean A, et al. Systemic corticosteroid rapidly reverses bronchodilator subsensitivity induced by formoterol in asthmatic patients. Am J Respir Crit Care Med 1997; 156: 28-35
59. Lipworth BJ, Aziz I. Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration. Chest 2000; 117: 156-62
60. Langley SJ, Masterson CM, Batty EP, et al. Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo. Eur Respir J 1998; 11: 1081-5
61. Wilding P, Clarc M, Coon JTL, et al. Effect of long term treatment with salmeterol on asthma control: a double blind, randomised crossover study. BMJ 1997; 314: 1441-7
62. Nelson HS, Berkowitz RB, Tinkelman DA, et al. Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma. Am J Respir Crit Care Med 1999; 159: 1556-61
63. Aziz I, Hall IP. McFarlane LC, et al. β2 adrenoreceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. J Allergy Clin Immunol 1998; 101: 337-41
64. Tattersfield AE. Tolerance to beta-agonists. Bull Eur Physiopathol Respir 1985; 21 (5): 1s-5s
65. Grove A, Lipworth BJ. Tolerance with β2 adrenoreceptor agonists: time for reappraisal. Br J Clin Pharmacol 1995; 39: 109-18
66. Hancox RJ, Aldridge RE, Cowan JO, et al. Tolerance to β-agonists during acute bronchoconstriction. Eur Respir J 1999; 14: 283-7
67. Elsasser S, Donna S, Demirozu CM, et al. Metaproterenol responsiveness after methacholine- and histamine-induced bronchoconstriction. Chest 1996; 110: 617-9
68. Davies AO, Lefkowitz RJ. Regulation of β-adrenergic receptor by steroid hormones. Ann Rev Physiol 1984; 46: 119-30
69. Collins S, Caron MG, Lefkowitz RJ. β-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem 1988; 263: 9067-70
70. Mak JCW, Nishikawa M, Barnes PJ. Glucocorticoids increase β2 adrenergic receptor transcription in human lung. Am J Physiol 1995; 268: L41-6
71. Davies AO, Lefkowitz RJ. Agonist promoted high affinity state of the β-adrenergic receptor in human neutrophils: modulation by corticoids. J Clin Endocrinol Metab 1980; 53: 703-38
72. Rodrigo G, Rodrigo C. Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 1998; 157: 698-703
73. Taylor DR, Hancox RJ. Interactions between corticosteroids and β2-agonists. Thorax 2000; 55: 595-602
74. Kalra S, Swytun VA, Bhagat R, et al. Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol. Chest 1996; 109: 953-6
75. Yates DH, Kharitonov SA, Barnes PJ. An inhaled corticosteroid does not prevent tolerance to the bronchoprotective effect of a long-acting inhaled β-agonist. Am J Respir Crit Care Med 1996; 154: 1603-7
76. Booth H, Bish R, Walter J, et al. Salmeterol tachyphylaxis in steroid treated asthmatics. Thorax 1996; 51: 1100-4
77. Simons FER, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effects of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 1997; 99: 655-9
78. Tan KS, McFarlane LC, Lipworth BJ. Concomitant administration of low dose prednisolone protects against in vivo β2 adrenoceptor subsensitivity induced by regular formoterol. Chest 1998; 113: 34-41
79. Giannini D, Bacci E, Dente FL, et al. Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of salmeterol. Chest 1999; 155: 629-34
80. Kraft M, Wenzel SE, Bettinger CM, et al. The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma. Chest 1997; 111: 1249-54
81. Holgate ST. The cellular and mediator basis of asthma in relation to natural history. Lancet 1997; 350: 8-9
82. Chung KF, Barnes PJ. Cytokines in asthma. Thorax 1999; 54: 825-57
83. Butchers PR, Vardey CJ, Johnson M. Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung. Br J Pharmacol 1991; 104: 672-6
84. Nials AT, Ball DI, Butchers PR, et al. Formoterol on airway smooth muscle and human lung mast cells: a comparison with salbutamol and salmeterol. Eur J Pharmacol 1994; 251: 127-35
85. Duffy ME, Hainan B, Ho S, et al. Regulation of epithelial light junctions permeability by cyclic AMP. Nature 1981; 29: 451-3
86. Advenier C, Qian Y, Koune JD, et al. Formoterol and salbutamol inhibit bradykinin-and histamine-induced airway vasular leakage in guinea-pig. Br J Pharmacol 1992; 105: 792-8
87. Baluk P, McDonald DM. The β2 adrenergic receptor agonist formoterol reduces microvascular leakage by inhibiting endothelial gap formation. Am J Physiol 1994; 226: L461-8
88. Bowden JJ, Sulakvelidze I, McDonald DM. Inhibition of neutrophil and eosinophil adhesion to venules of rat trachea by β2-adrenergic agonist formoterol. J Appl Physiol 1994; 77: 397-405
89. Bolton PB, Lefevre P, McDonald DM. Salmeterol reduces early-and late phase plasma leakage and leukocyte adhesion in rat airways. Am J Respir Crit Care Med 1997; 155: 1428-35
90. Tokyama K, Lötvall JO, Löfdahl CG, et al, Inhaled formoterol inhibits histamine-induced airflow obstruction and airway microvascular leakage. Eur J Pharmacol 1991; 193: 35-9
91. Whelan CJ, Johnson M. Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea-pig lung and skin. Br J Pharmacol 1992; 105: 831-8
92. Whelan CJ, Johnson M, Vardey CJ. Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guineas-pig skin and lung. Br J Pharmacol 1993; 110: 613-8
93. Ottonello L, Morone P, Dapino P, et al. Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils. Clin Exp Immunol 1996; 106: 97-102
94. Sanjar S, McCabe PJ, Humbles AH. Inhibition by salmeterol of antigen-induced eosinophil accumulation in guineas pig lung. Eur Respir J 1991; 4 Suppl. 13-14: 200s
95. Anderson GP. Pharmacology of formoterol: an innovative bronchodilator. Agents Actions 1991; 34: 97-115
96. Eda R, Sugiyama H, Hopp RJ, et al. Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation. Int Arch Allergy Immunol 1993; 102: 391-8
97. Bolton PB, Lefevre P, McDonald DM. Salmeterol reduces early-and late phase plasma leakage and leukocyte adhesion in rat airways. Am J Respir Crit Care Med 1997; 155: 1428-35
98. Erjefält I, Persson CG. Long duration and high potency of anti-oxidative effects of formoterol in guinea-pig tracheobronchial airways. Am Rev Respir Dis 1991; 144: 778-91
99. Aalbers R, De Monchy JGR, Kauffman HF, et al. Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction. Eur Respir J 1993; 6: 840-7
100. Woolley KL, Ådelroth E, Woolley MJ, et al. Effects of allergen challenge on eosinophils, eosinophil cationic protein and granulocyte-macrophage colony-stimulating factor in mild asthma. Am J Respir Crit Care Med 1995; 151: 1915-24
101. Pin I, Freitag AP, O'Byrne PM, et al. Changes in the cellular profile of induced-sputum after allergen-induced asthmatic responses. Am Rev Respir Dis 1992; 145: 1265-9
102. Weersink EJ, Postma DS, Aalbers R, et al. Early and late asthmatic reaction after allergen challenge. Respir Med 1994; 88: 103-14
103. De Monchy JGR, Kauffman HF, Venge P, et al. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am Rev Respir Dis 1985; 131: 373-6
104. Twentyman OP, Finnery JP, Harris A, et al. Protection against allergen-induced asthma by salmeterol. Lancet 1990; 236: 1338-42
105. Wong BJ, Dolovich J, Ramsdale EH, et al. Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Respir Dis 1992; 146: 1156-60
106. Weersink EJ, Aalbers R, Koëter GH, et al. Partial inhibition of the early and late asthmatic response by a single dose of salmeterol. Am J Respir Crit Care Med 1994; 150: 1262-7
107. Pizzichini MM, Kidney JC, Wong BJ, et al. Effect of salmeterol compared with beclomethasone on allergen-induced asthmatic and inflammatory responses. Eur Respir J 1996; 9: 449-55
108. Taylor DA, Jenssen MW, Aikman SL, et al. Comparison of salmeterol and albuterol-induced bronchoprotection against and histamine in mild asthma. Am J Respir Crit Care Med 1997; 156: 1731-7
109. Solèr M, Joos L, Bolliger CT, et al. Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine-and AMP induced bronchoconstriction. Eur Respir J 1994; 7: 1973-7
110. Nightingale JA, Rogers DF, Barnes PJ. Differential effect of formoterol on adenosine monophosphate and histamine reactivity in asthma. Am J Respir Crit Care Med 1999; 159: 1786-90
111. Rabe KF, Giembycz MA, Dent G, et al. Salmeterol is a competitive antagonist at β-adrenoceptors mediating inhibition of respiratory burst in guinea-pig eosinophils. Eur J Pharmacol 1993; 231: 305-8
112. Giannini D, Carletti A, Dente FL, et al. Tolerance to the bronchoprotective effect of salmeterol on allergen challenge. Chest 1996; 110: 1452-7
113. Aziz I, Tan TS, Hall IP, et al. Subsensitivity to bronchoprotection against adenosine monophosphate challenge following regular once-daily formoterol. Eur Respir J 1998; 12: 580-4
114. Aziz I, Wilson AM, Lipworth BJ. Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers is asthmatic adults. Chest 2000; 118: 1049-52
115. Palmqvist M, Balder B, Löwhagen O, et al. Late asthmatic reaction decreased after pretreatment with salbutamol and formoterol, a new long-acting β2 agonist. J Allergy Clin Immunol 1992; 89: 844-9
116. Dente FL, Bancalari L, Bacci E, et al. Effect of a single dose of salmeterol on the increase on the airway eosinophils induced by allergen challenge in asthmatic subjects. Thorax 1999; 54: 622-4
117. Pedersen B, Dahl R, Larsen BB, 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. Allergy 1993; 48: 377-82
118. Anderson GP. Interactions between corticosteroids and . Am J Respir Crit Care Med 2000; 161 (3 pt 2): S188-96
119. Calhoun WJ, Hinton KL, Kratzenberg J. The effect of salmeterol on markers of airway inflammation following segmental allergen challenge. Am J Respir Crit Care Med 2001; 163: 881-6
120. Roberts JA, Bradding P, Britten KM, et al. The long-acting β2 agonist salmeterol xinafoate: effects on airway inflammation in asthma. Eur Respir J 1999; 14: 275-82
121. Gardiner PV, Ward C, Booth H, et al. Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics. Am J Respir Crit Care Med 1994; 150: 1006-11
122. Li X, Ward C, Thien F, et al. An anti-inflammatory effect of salmeterol, a long-acting β2 agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma. Am J Respir Crit Care Med 1999; 160: 1493-9
123. Boulet LP, Chakir J, Milot J, et al. Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma. Clin Exp Allergy 2001; 31: 430-47
124. Aziz I, Wilson AM, Lipworth BJ. Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults. Chest 2000; 118: 1049-52
125. Wallin A, Sandström T, Söderberg M, et al. The effects of regular inhaled formoterol, budesonide and placebo on mucosal inflammation and clinical indices in mild asthma. Am J Respir Crit Care Med 1999; 159: 79-86
126. Kips JC, O'Connor BJ, Inman MD, et al. A long-term study of anti-inflammatory effect of low-dose budesonide plus formoterol versus high dose budesonide in asthma. Am J Respir Crit Care Med 2000; 161: 996-1001
127. Goldstein MF, Veza BA, Dunsky EH, et al. Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV1 responses, and methacholine inhalation challenges in the evaluation of suspected asthma. Chest 2001; 119: 1001-10
128. Maesen BL, Westermann CJ, Duurkens VA, et al. Effects of formoterol in apparently poorly reversible chronic obstructive pulmonary disease. Eur Respir J 1999; 13: 1103-8
129. Molimard M, Bourceareau J, LeGris V, et al. Comparison between Formoterol 12 μg bid and on demand albuterol in moderate persistent asthma. Respir Med 2001; 95 (1): 64-70
130. Bensch G, Lapidus RJ, Levine RJ, et al. A randomized, 12 week, double-blind, placebo controlled study comparing formoterol dry powder inhaler with salbutamol metered dose inhaler. Ann Allergy Asthma Immunol 2001; 86 (1): 19-27
131. Van der Molen T, Postma DS, Turner MO, et al. Effects of the long acting β agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. Thorax 1997; 52: 535-9
132. Ekström T, Ringdal N, Sobradillo V, et al. Low-dose formoterol Turbuhaler (Oxis) BID, a 3 month placebo-controlled comparison with terbutaline q.i.d. Respir Med 1998; 92 (8): 1040-5
133. Wallin A, Melander B, Rosenhall L, et al. Formoterol, a new long-acting β2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma. Thorax 1990; 45: 259-61
134. Midgren B, Melander B, Persson G. Formoterol, a new long acting β2 agonist, inhaled twice daily, in stable asthmatic subjects. Chest 1992; 101: 1019-22
135. Steffensen I, Faurschou P, Riska H, et al. Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol. Allergy 1995; 50: 657-63
136. Kesten S, Chapman KR, Broder I, et al. A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. Am Rev Respir Dis 1991; 144: 622-5
137. Arvidson P, Larsson S, Löfdahl C-G, et al. Inhaled formoterol during one year in asthma: a comparison with salbutamol. Eur Respir J 1991; 4: 1168-73
138. Kemp JP, Cook DA, Incaudo GA, et al. Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group. J Allergy Clin Immunol 1998; 191 (2 Pt 1): 188-95
139. Lockey RF, DuBuske LM, Friedman B, et al. Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Chest 1999; 115: 666-73
140. Pearlman DS, Chervinski P, LaForce C, et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med 1992; 327: 1420-5
141. D'Alonzo GE, Nathan RA, Henochowicz S, et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA 1994; 271: 1412-6
142. Jones KP. Salmeterol xinafoate in the treatment of mild to moderate asthma in primary care. Thorax 1994; 49: 971-5
143. Juniper EF, Johnston PR, Borkhoff CM, et al. Quality of life in asthma clinical trials: comparison of salmeterol and salbutamol. Am J Respir Crit Care Med 1995; 151: 66-70
144. Leblanc P, Knight A, Kreisman H, et al. A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma. Am J Respir Crit Care Med 1996; 154: 324-8
145. Taylor DR, Town GI, Herbison GP, et al. Asthma control during long term treatment with regular inhaled salbutamol and salmeterol. Thorax 1998; 53: 744-52
146. Wenzel SE, Lumry W, Manning M, et al. Efficacy, safety and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma. Ann Allergy Asthma Immunol 1998; 80 (6): 463-70
147. Britton MG, Earnshaw JS, Palmer JBD. A twelve month comparison of salmeterol with salbutamol in asthmatic patients. Ear Respir J 1992; 5: 1062-7
148. Boulet LP, Laviolette M, Boucher S, et al. A twelve-week comparison of salmeterol and salbutamol in the treatment of mild to moderate asthma: a Canadian multicenter study. J Allergy Clin Immunol 1997; 99: 13-21
149. Lundback B, Rawlinson DW, Palmer JBD. Twelve month comparison of salmeterol and salbutamol as dry powder in asthmatic patients. Thorax 1993; 48: 148-53
150. Hermansson BA, Jenkins RJ. A 4-week comparison of salmeterol and terbutaline in adult asthma. Allergy 1995; 50: 551-8
151. Greening AP, Ind PW, Nothfield M, et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allan & Hanburys Limited UK Study Group. Lancet 1994; 344: 219-24
152. Kelsen SG, Church NL, Gillman SA, et al. Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled steroids: a randomized clinical trial. J Asthma 1999; 36: 703-15
153. Murray JJ, Church NL, Anderson WH, et al. Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases. Allergy Asthma Proc 1999; 20: 173-80
154. Condemi JJ, Goldstein S, Kalberg C, et al. The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma. Salmeterol Study Group. Ann Allergy Asthma Immunol 1999; 82: 383-9
155. Vermetten FAAM, Boermans AJM, Luiten WDVF, et al. Comparison of salmeterol with beclomethasone in adult patients with mild persistent asthma who are already on low-dose inhaled steroids. J Asthma 1999; 6: 97-106
156. Van Noord JA, Schreurs AJM, Mol SJM, et al. Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma. Thorax 1999; 54: 207-12
157. Weersing EJ, Douma RR, Postma DS, et al. Fluticasone propionate, salmeterol xinafoate, and their combination in the treatment of nocturnal asthma. Am J Respir Crit Care Med 1997; 155: 1241-6
158. Baraniuk J, Murray JJ, Nathan RA, et al. Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma. Chest 1999; 116: 625-32
159. Pauwels R, Löfdahl C-G, Postma DS, et al. For the Formoterol and corticosteroids establishing therapy (FACET) international study group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997; 337: 1405-11
160. Bouros D, Bachlitzanakis N, Kottakis J, et al. Formoterol and beclomethasone versus higher dose beclomethasone as maintenance therapy in adult asthma. Eur Respir J 1999; 14: 627-32
161. Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000; 320: 1368-71
162. Ind PW, Dal Negro R, Colman N, et al. Inhaled fluticasone propionate and salmeterol in moderate adult asthma. I. Lung function and symptoms [abstract]. Am J Respir Crit Care Med 1998; 157: A416
163. Ind PW, Dal Negro R, Colman N, et al. Inhaled fluticasone propionate and salmeterol in moderate adult asthma. II Exacerbations [abstract]. Am J Resp Crit Care Med 1998; 157: A415
164. Kalberg CJ, Nelson H, Yancey S, et al. A comparison of added salmeterol versus increased-dose fluticasone in patients symptomatic on low-dose fluticasone. J Allergy Clin Immunol 1998; 102: S6
165. Pauwels RA. Additive effect of inhaled formoterol and budesonide in reducing asthma exacerbations. Allergy 1998; 53: 20-3
166. Manolitsas DN, Wang J, Devalia JL, et al. Regular albuterol, nedocromil sodium, and bronchial inflammation in asthma. Am J Respir Crit Care Med 1995; 151: 1925-30
167. Pizzichini E, Pizzichini MMM, Efthimiades A, et al. Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood. J Allergy Clin Immunol 1997; 99: 539-44
168. Low dose of inhaled budesonide and formoterol in mild persistent asthma. O'Byrne PM, Barnes PJ, Rodrigues-Roisin R. Am J Respir Crit Care Med 2001; 164: 1392-7
169. McIvor RA, Pizzichini E, Turner MO, et al. Potential masking effects of salmeterol on airway inflammation in asthma. Am J Respir Crit Care Med 1998; 158: 924-50
170. Arvidsson P, Larsson S, Löfdahl C-G, et al. Inhaled formoterol during one year in asthma: a comparison with salbutamol. Eur Respir J 1991; 4: 1168-73
171. Nielsen LP, Pedersen B, Faurschou P, et al. Salmeterol reduces the need for inhaled corticosteroids in steroid-dependent asthmatics. Respir Med 1999; 93: 863-8
172. Wilding P, Clark M, Coon JT, et al. Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study. BMJ 1997; 314: 1441-6
173. Tattersfield AE, Postma DS, Barnes PJ, et al. Exacerbations of asthma, a descriptive study of 425 severe exacerbations. The FACET international group. Am J Respir Crit Care Med; 1999; 160: 594-9
174. Gibson PG, Norzila MZ, Fakes K, et al. Pattern of airway inflammation and its determinants in children with acute severe asthma. Pediatr Pulmonol 1999; 28: 261-70
175. Tintinger GR, Anderson R, Theron AJ, et al. Comparison of the effects of selective and non-selective beta-adrenoceptor agonists on the pro-inflammatory activities of human neutrophils in vitro. Inflammation 2000; 24: 239-49
176. Pearlman DS, Stricker W, Weinstein S, et al. Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma. Ann Allergy Asthma Immunol 1999; 82: 257-65
177. Taylor DR, Sears MR, Herbison GP, et al. Regular inhaled β-agonist in asthma: effects on exacerbations and lung function. Thorax 1993; 48: 134-8
178. Drazen JM, Israel E, Boushey HA, et al. Comparison of
179. Dennis SM, Sharp SJ, Vickers MR, et al. Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task force and the MRC General Practice Research Framework. Lancet 2000; 355: 1675-9
180. Gauvreau GM, Jordana M, Watson RM, et al. Effect of regular inhaled albuterol on allergen-induced late responses and sputum eosinophils in asthmatic subjects. Am J Respir Crit Care 1997; 156: 1738-45
181. Verberne AAPH, Frost C, Roorda RJ, et al. The Dutch Pediatric Asthma Study Group. One year treatment with salmeterol compared with beclomethasone in children with asthma. Am J Respir Crit Care Med 1997; 156: 688-95
182. Simons FE. A comparison of beclomethasone, salmeterol and placebo in children with asthma. Canadian Beclomethasone Dipropionate Salmeterol Xinafoate Study Group. N Engl J Med 1997; 337: 1659-65
183. Nathan RA, Pinnas JL, Schwartz HJ, et al. A six-month placebo-controlled comparison of the safety and efficacy of salmeterol or beclomethasone for persistent asthma. Ann Allergy Asthma Immunol 1999; 82: 521-9
184. Turner MO, Johnston PR, Pizzichini E, et al. Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, placebo controlled trial. Can Respir J 1998; 5: 261-8
185. Shapiro G, Lumry W, Wolfe J, et al. Combined salmeterol 50μg and fluticasone propionate 250μg in the Discus Device for the treatment of asthma. Am J Respir Crit Care Med 2000; 161: 527-34
186. Kavuru M, Melamed J, Gross G, et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: A randomized, double blind, placebo controlled trial. J Allergy Clin Immunol 2000; 105: 1108-16
187. Konermann M, Lück G, Rawert B, et al. Effect of the long-acting β2 agonist inhalant Formoterol on the quality of sleep of patients with bronchial asthma. Pneumonologie 2000; 54: 104-9
188. Clauzel AM, Molimard M, Le Gros V, et al. Use of formoterol dry powder administered for three-months via a single dose inhaler in 1380 asthmatic patients. J Investig Allergol Clin Immunol 1998; 8: 265-70
189. Maesen FP, Smeets JJ, Gubbermans HL, et al. Formoterol in the treatment of nocturnal asthma. Chest 1990; 98: 866-70
190. Martin RJ, Kraft M, Beaucher WN, et al. Comparative study of extended release albuterol sulfate and long-acting inhaled salmeterol xinafoate in the treatment of nocturnal asthma. Ann Allergy Asthma Immunol 1999; 83: 121-6
191. Faurschou P, Engel A, Haanaes O. Salmeterol in two different doses in the treatment of nocturnal bronchial asthma poorly controlled by other therapies. Allergy 1994; 49: 827-32
192. Weersink EJ, Van Zomeren EH, Koëter GH, et al. Treatment of nocturnal airway obstruction improves daytime cognitive performance. Am J Respir Crit Care Med 1994; 156: 1144-55
193. Boner AL, Spezia E, Piovesan P, et al. Inhaled formoterol in the prevention of exercise induced bronchoconstriction in asthmatic children. Am J Respir Crit Care Med 1994; 149: 935-9
194. Evidence of the rapid protective effect of formoterol dry-powder inhalation against exercise-induced bronchospasm in athletes with asthma. Ferrari M, Balestreri F, Baratieri S, et al. Respiration 2000; 67 (5): 510-3
195. Anderson SD, Rodwell LT, Du Toit J, et al. Duration of protection by inhaled salmeterol in exercise-induced asthma. Chest 1991; 100: 1254-60
196. Grönneröd TA, Von Berg A, Schwabe G, et al. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 h in children and adolescents. Respir Med 2000; 94: 661-7
197. Bronsky EA, Pearlman DS, Pobiner BF, et al. Prevention of exercise induced bronchospasm in pediatric asthma patients. A comparison of two salmeterol delivery devices. Pediatrics 1999; 104: 501-6
198. De Benedictis FM, Tuteri G, Pazzelli P, et al. Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses. Eur Respir J 1996; 9: 2099-103
199. Schaanning J, Vilsvik J, Henriksen AH, et al. Efficacy and duration of salmeterol powder inhalation in protecting against exercise-induced bronchoconstriction. Ann Allergy Asthma Immunol 1996; 76: 57-60
200. Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994; 88: 363-8
201. Nelson JA, Strauss L, Skowronski M, et al. Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 1998; 339: 141-6
202. Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double blind trial. Exercise study group. Ann Intern Med 2000; 132: 97-104
203. In't Veen JCCM, Beekman AJ, Bel EH, et al. Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes. Am J Respir Crit Care Med 2000; 161: 1902-6
204. Booms P, Cheung D, Timmers MC, et al. Protective effect of inhaled budesonide against unlimited airway narrowing to methacholine in atopic patients with asthma. J Allergy Clin Immunol 1997; 99: 330-7
205. Kraft M, Martin RJ, Wilson S, et al. Lymphocyte and eosinophil influx into alveolar airway tissue in nocturnal asthma. Am J Respir Crit Care Med 1999; 159: 228-34
206. Politiek M, Boorsma M, Aalbers R. Comparison of formoterol, salbutamol and salmeterol in methacholine-induced severe bronchoconstriction. Eur Respir J 1999; 13 (5): 988-92
207. Eickelberg O, Roth M, Lorx R, et al. Ligand-independent binding activation of the glucocorticoid receptor by β2 adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 1999; 274: 1005-10
208. Oddera S, Silvestri M, Testi R, et al. Salmeterol enhances the inhibitory activity of dexamethasone on allergen-induced blood mononuclear cell activation. Respiration 1998; 65: 199-204
209. Dowling RB, Johnson M, Cole PJ, et al. Effect of salmeterol on haemophilus influenza infection of respiratory mucosa in vitro. Eur Respir J 1998; 11: 86-90
210. Dowling RB, Rayner CF, Rutman A, et al. Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa. Am J Respir Crit Care Med 1997; 155: 327-36
211. Korn SH, Jerre A, Brattsand R. Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells. Eur Respir J 2001; 17: 1070-7
212. Orsida BE, Ward C, Li X, et al. Effect of a long-acting β2-agonist over three months on airway remodeling in asthma. Am J Respir Crit Care Med 2001; 164: 117-21
213. Van Noord JA, Smeets JJ, Raaijmakers JAM, et al. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. Eur Respir J 1996; 9: 1684-8
214. Beach JR, Young CL, Stenton SC, et al. A comparison of the speeds of action of salmeterol and salbutamol in reversing methacholine-induced bronchoconstriction. Pulm Pharmacol 1992; 5: 133-5
215. Beach JR, Bromly CL, Avery AJ, et al. Speeds of action of single doses of formoterol and salbutamol compared with placebo in reversing methacholine-induced bronchoconstriction. Pulm Pharmacol 1996; 9: 245-9
216. Campbell LM, Anderson TJ, Parashchak MR, et al. A comparison of the efficacy of long-acting β2 agonists: eformoterol via Turbuhaler and salmeterol via pressurized metered dose inhaler or Accuhaler™, in mild to moderate asthmatics, Force Research Group. Respir Med 1999; 93: 236-44
217. Vervloet D, Ekström T, Pela R, et al. A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease. Respir Med 1998; 92: 836-42
218. Rutten-van Mölken MPMH, Doorslaer EKA, Till MD. Cost effectiveness analysis of formoterol versus salmeterol in patients with asthma. Pharmacoeconomics 1998; 14: 671-84
219. Tattersfield AE, Löfdahl C-G, Postma DS, et al. Comparison of formoterol and terbutaline for as needed treatment of asthma: a randomised trial. Lancet 2001; 357: 257-61
220. Bennett JA, Harrison TW, Tattersfield AE. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects. Eur Respir J 1999; 13: 445-8
221. Tötterman KJ, Huhti L, Sutinen E, et al. Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3 days in stable asthmatic patients. Eur Respir J 1998; 12: 573-9
222. Guhan AR, Cooper S, Oborne J, et al. Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects. Thorax 2000; 55: 650-6
223. Lipworth BJ, Struthers AD, McDevitt DG. Tachyphylaxis to systemic but not airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics. Am Rev Respir Dis 1989; 140: 586-92
224. Larsson PT, Martinsson A, Olsson G, et al. Altered adrenoceptor responsiveness during adrenaline infusion but not during mental stress: differences between receptor subtypes and tissues. Br J Clin Pharmacol 1989; 28: 663-74
225. Aziz I, McFarlane LC, Lipworth BJ. Concomitant inhaled corticosteroids resensitises cardiac β2 -adrenoceptors in the presence of long-acting β2 agonist therapy. Eur J Clin Pharmacol 1998; 54: 377-81
226. Maconochie JG, Minton NA, Chilton JE, et al. Does tachyphylaxis occur to the non-pulmonary effects of salmeterol? Br J Clin Pharmacol 1994; 37: 199-204
227. Burgess C, Ayson M, Rajasingham S, et al. The extrapulmonary effects of increasing doses of formoterol in patients with asthma. Eur J Clin Pharmacol 1998; 54: 141-7
228. Bennett JA, Smyth ET, Pavord ID, et al. Systemic effects of salbutamol and salmeterol in patients with asthma. Thorax 1994; 49: 771-4
229. Bennett JA, Tattersfield AE. Time course and relative dose potency of systemic effects from salmeterol and salbutamol in healthy subjects. Thorax 1997; 52: 458-64
230. Bremner P, Woodman K, Burgess C, et al. A comparison of the cardiovascular and metabolic effects of formoterol, salbutamol and fenoterol. Eur Respir J 1993; 6: 204-10
231. Decker N, Quennedey MC, Rouot B, et al. Effects of N-aralkyl substitution of β agonists on α and β adrenoceptors subtypes: pharmacological studies and binding assays. J Pharm Pharmacol 1982; 34: 107-12
232. Maesen FP, Costongs R, Smeets JJ, et al. The effect of maximal doses of formoterol and salbutamol from a metered dose inhaler on pulse rates, ECG, and serum potassium concentrations. Chest 1991; 99: 1367-73
233. Leitch AG, Clancy LJ, Costello JF, et al. Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal man. BMJ 1976; 1: 365-7
234. Bremner P, Burgess C, Crane J, et al. Cardiovascular effects of fenoterol under conditions of hypoxemia. Thorax 1992; 47: 814-7
235. Bremner P, Burgess C, McHaffie D, et al. The effect of hypercapnia and hypoxaemia on the cardiovascular responses to isoprotenerol. Clin Pharmacol Ther 1994; 56: 302-8
236. Kiely DG, Cargill RI, Lipworth BJ. Effects of hypercapnia on hemadynamic, inotropic, lusitropic and electric indices in humans. Chest 1996; 109: 1215-21
237. Kiely DG, Cargill RI, Grove A, et al. Abnormal myocardial repolarisation in response to hypoxemia and fenoterol. Thorax 1995; 50: 1062-6
238. Jenne JW. Physiologic actions of beta-adrenergic agonists. In: Leff AR, editor. Pulmonary and critical care pharmacology and therapeutics. New York: McGraw-Hill, 1996: 473-87
239. Viegas CA, Ferrer A, Montserrat JM, et al. Ventilation-perfusion response after fenoterol in hypoxemic patients with stable COPD. Chest 1996; 110: 71-7
240. Wong CS, Pavord ID, Williams J, et al. Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990; 336: 1396-9
241. Cazzola M, Imperatore F, Salzillo A, et al. Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia. Chest 1998; 114: 411-5
242. Crane J, Pearce NE, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83. Case-control study. Lancet 1989; I: 917-22
243. Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand. 1977-81. Thorax 1990; 45: 170-5
244. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study. Thorax 1991; 46: 105-11
245. Mullen M, Mullen B, Caray M. The association between beta agonist use and death from asthma. A meta-analytic intergration of case-control studies. JAMA 1993; 270: 1842-5
246. Spitzer WO, Suissa S, Ernst P, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med 1992; 326: 560-1
247. Suissa S, Ernst P, Boivin J, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994; 149: 604-10
248. Abramson MJ, Bailey MJ, Couper FJ, et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001; 163: 12-8
249. Turner MO, Noertjojo K, Vedal S, et al. Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med 1998; 157: 1804-9
250. Molfino NA, Nannini LJ, Martelli AN, et al. Respiratory arrest in near-fatal asthma. N Engl J Med 1991; 324: 285-8
251. Beasley R, Pearce N, Crane J, et al. Beta-agonists: what is the evidence that their use increases the risk of asthma morbidity and mortality? J Allergy Clin Immunol 1999; 1004 (2 Pt 2): S18-30
252. Castle W, Fuller R, Hall J, et al. Serevent nation-wide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993; 306: 1034-7
253. Boulet LP, Turcotte H, Cartier A, et al. Influence of beclomethasone and salmeterol on the perception of methacholineinduced bronchoconstriction. Chest 1998; 114: 373-9
254. Bel EH, Zwinderman AH, Timmers MC, et al. The protective effect of a β2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease. Thorax 1991; 46: 9-14
255. 2 agonists. Eur Respir J. In press
256. Horn CR, Clark TJ, Cochrane GM. Compliance with inhaled therapy and morbidity from asthma. Respir Med 1990; 84: 67-70
257. Castellsague J, Garcia-Rodriguez LA, Pérez-Gutthann S, et al. Characteristics of users of inhaled long-acting β2 agonists in a southern European population. Respir Med 1999; 93: 709-14
258. Van der Woude HJ, Aalbers R. Compliance with inhaled glucocorticoids and concomitant use of long-acting β2 agonists. Respir Med. In press
259. Agtertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88: 373-81
260. Overbeek SE, Kerstjens HAM, Bogaard JM, et al. Is delayed introduction of inhaled corticosteroids harmful in patients with obstructive airways disease (asthma and COPD?). Chest 1996; 110: 35-41
261. Van Essen-Zandvliet EEM, Hughes MD, Waalkens HJ, et al. Remission of childhood asthma after long-term treatment with an inhaled corticosteroid (budesonide): can it be achieved? Eur Respir J 1994; 7: 63-8
262. Meijer GG, Postma DS, Mulder PGH, et al. Long term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids. Am J Respir Crit Care Med 1995; 152: 1887-9
263. Russell G, Willians DA, Weller P, et al. Salmeterol Xinofoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol 1995; 75: 423-8
264. Langton Hewer S, Hobbs J, et al. Pilgrim's progress: the effect of salmeterol in older children with chronic severe asthma. Respir Med 1995; 89: 435-40
265. Akpinarli A, Tuncer A, Saraclar Y, et al. Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial. Arch Dis Child 1999; 81: 45-8
266. Byrnes C, Shrewsbury S, Barnes PJ, et al. Salmeterol in paediatric asthma. Thorax 2000; 55: 780-4
267. Verberne AAPH, Frost C, Duiverman EJ, et al. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998; 158: 213-9
268. Bisgaard H. Long-acting β2 agonists in management of childhood asthma: a critical review of the literature. Pediatr Pulmonol 2000; 29: 221-34
269. Heuck C, Heickendorff L, Wolthers OD. A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide. Arch Dis Child 2000; 83: 224-9