Meta-analysis: Effect of long-acting β-agonists on severe asthma exacerbations and asthma-related deaths

Annals of Internal Medicine

Volumn 144, Issue 12, 2006, Pages 904-912

  Salpeter, Shelley R ^a   Buckley, Nicholas S ^b   Ormiston, Thomas M ^a   Salpeter, Edwin E ^c  

^a SANTA CLARA VALLEY MEDICAL CENTER   (United States)

^b Space Sciences Building ^*  (United States)

^c Department of Obstetrics Gynecology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTEROID; FORMOTEROL; SALBUTAMOL; SALMETEROL; TRIAMCINOLONE; ANTIASTHMATIC AGENT; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BRONCHODILATING AGENT; DRUG DERIVATIVE; ETHANOLAMINE DERIVATIVE;

ARTIFICIAL VENTILATION; ASTHMA; CLINICAL TRIAL; COCHRANE LIBRARY; DISEASE EXACERBATION; DISEASE SEVERITY; EMBASE; FOOD AND DRUG ADMINISTRATION; HOSPITALIZATION; HUMAN; INTUBATION; MEDLINE; META ANALYSIS; PRIORITY JOURNAL; REVIEW; RISK; RISK ASSESSMENT; SYSTEMATIC REVIEW; ADULT; ARTICLE; CHILD; CONTROLLED CLINICAL TRIAL; DRUG ADMINISTRATION; FEMALE; MALE; MORTALITY; RANDOMIZED CONTROLLED TRIAL; RECURRENT DISEASE; RISK FACTOR; STATISTICS; TREATMENT OUTCOME;

ADRENERGIC BETA-AGONISTS; ADULT; ALBUTEROL; ANTI-ASTHMATIC AGENTS; ASTHMA; BRONCHODILATOR AGENTS; CHILD; DRUG ADMINISTRATION SCHEDULE; ETHANOLAMINES; FEMALE; HOSPITALIZATION; HUMANS; MALE; RANDOMIZED CONTROLLED TRIALS; RECURRENCE; RISK FACTORS; TREATMENT OUTCOME;

EID: 33745306721     PISSN: 00034819     EISSN: None     Source Type: Journal    
DOI: 10.7326/0003-4819-144-12-200606200-00126     Document Type: Review

References (105)

1. Kips JC, Pauwels RA. Long-acting inhaled beta(2)-agonist therapy in asthma. Am J Respir Crit Care Med. 2001;164:923-32.
2. Haahtela T, Jarvinen M, Kava T, Kiviranta K, Koskinen S, Lehtonen K, et al. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med. 1991;325:388-92.
3. van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF. Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group. Am Rev Respir Dis. 1992;146:547-54.
4. 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.
5. Verberne AA, Frost C, Roorda RJ, van der Laag H, Kerrebijn KF. One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group. Am J Respir Crit Care Med. 1997;156:688-95.
6. National Heart, Lung, and Blood Institute. Guidelines for Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; 1997.
7. National Heart, Lung, and Blood Institute. Guidelines for the Diagnosis and Management of Asthma. Update on Selected Topics 2002. Bethesda, MD: National Institutes of Health; 2002.
8. Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ. 2000;320:1368-73.
9. O'Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001;164:1392-7.
10. Kelman GR, Palmer KN, Cross MR. Cardiovascular effects of AH.3365 (salbutamol). Nature. 1969;221:1251.
11. Dodds WN, Soler NG, Thompson H. Letter: Deaths in asthma. Br Med J. 1975;4:345.
12. Crompton GK. Letter: Death in asthma. Br Med J. 1975;4:458.
13. Fahy JV, Boushey HA. Controversies involving inhaled beta-agonists and inhaled corticosteroids in the treatment of asthma. Clin Chest Med. 1995;16:715-33.
14. Taylor DR, Sears MR, Cockcroft DW. The beta-agonist controversy. Med Clin North Am. 1996;80:719-48.
15. Salpeter SR, Ormiston TM, Salpeter EE. Meta-analysis: respiratory tolerance to regular beta2-agonist use in patients with asthma. Ann Intern Med. 2004;140:802-13.
16. Lipworth BJ. Risks versus benefits of inhaled beta 2-agonists in the management of asthma. Drug Saf. 1992;7:54-70.
17. Suissa S, Blais L, Ernst P. Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J. 1994;7:1602-9.
18. Kraan J, Koeter GH, vd Mark TW, Sluiter HJ, de Vries K. Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline. J Allergy Clin Immunol. 1985;76:628-36.
19. Sears MR, Taylor DR, Print CG, Lake DC, Li QQ, Flannery EM, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet. 1990;336:1391-6.
20. Wahedna I, Wong CS, Wisniewski AF, Pavord ID, Tattersfield AE. Asthma control during and after cessation of regular beta 2-agonist treatment. Am Rev Respir Dis. 1993;148:707-12.
21. Johnson M. The beta-adrenoceptor. Am J Respir Crit Care Med. 1998;158:S146-53.
22. U.S. Food and Drug Administration. Study of asthma-drug halted. FDA Talk Paper. 2003:T03-06.
23. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.
24. U.S. Food and Drug Administration Advisory Committee. Serevent, Advair, Foradil withdrawals to be considered by Advisory Committee. 2005. Accessed at www.fdaadvisorycommittee.com/FDC/AdvisoryCommittee/Committees/ Pulmonary-Allergy%20Drugs/071305_betasafety/071305_BroncoP.htm on 8 August 2005.
25. U.S. Food and Drug Administration. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Pulmonary and Allergy Drugs Advisory Committee. Transcript of 13 July 2005 meeting. Accessed at www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4148T1.pdf on 5 September 2005.
26. U.S. Food and Drug Administration. FDA Public Health Advisory. Serevent, Advair, Foradil. 2005. Accessed at www.fda.gov/cder/drug/advisory/ LABA.htm on 11 December 2005.
27. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.
28. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273:408-12.
29. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719-48.
30. Berlin JA, Laird NM, Sacks HS, Chalmers TC. A comparison of statistical methods for combining event rates from clinical trials. Stat Med. 1989;8:141-51.
31. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326:219.
32. Bensch G, Lapidus RJ, Levine BE, Lumry W, Yegen U, Kiselev P, et al. A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. Ann Allergy Asthma Immunol. 2001;86:19-27.
33. Bensch G, Berger WE, Blokhin BM, Socolovsky AL, Thomson MH, Till MD, et al. One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma. Ann Allergy Asthma Immunol. 2002;89:180-90.
34. Busse W, Levine B, Andriano K, Lavecchia C, Yegen U. Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. Clin Ther. 2004;26:1587-98.
35. D'Urzo AD, Chapman KR, Cartier A, Hargreave FE, Fitzgerald M, Tesarowski D. Effectiveness and safety of salmeterol in nonspecialist practice settings. Chest. 2001;119:714-9.
36. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, et al. Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA. 2001;285:2583-93.
37. Levy R, Pinnas JL, Milgrom H, Smith J, Yegen U. Safety and efficacy in children with persistent asthma treated with formoterol 10 mcg BID delivered via Certihaler: a novel multidose dry-powder inhaler. Pediatric Asthma, Allergy, and Immunology. 2005;18:25-35.
38. Lockey RF, DuBuske LM, Friedman B, Petrocella V, Cox F, Rickard K. Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Chest. 1999;115:666-73.
39. Price D, Dutchman D, Mawson A, Bodalia B, Duggan S, Todd P, et al. Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose. Thorax. 2002;57:791-8.
40. Rosenthal RR, Busse WW, Kemp JP, Baker JW, Kalberg C, Emmett A, et al. Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness. Chest. 1999;116:595-602.
41. Steffensen I, Faurschou P, Riska H, Rostrup J, Wegener T. 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.
42. Taylor DR, Town GI, Herbison GP, Boothman-Burrell D, Flannery EM, Hancox B, et al. Asthma control during long-term treatment with regular inhaled salbutamol and salmeterol. Thorax. 1998;53:744-52.
43. U.S. Food and Drug Administration. Center for Drug Evaluation and Review. Foradil (Formoterol Fumarate inhalation) aerolizer. Part 4. 2001. Accessed at www.fda.gov/cder/foi/nda/2001/20831_Foradil_medr_P4.pdf on 3 September 2005.
44. U.S. Food and Drug Administration. Center for Drug Evaluation and Review. Foradil (Formoterol Fumarate inhalation) aerolizer. Part 5. 2001. Accessed at www.fda.gov/cder/foi/nda/2001/20831_Foradil_medr_P5.pdf on 3 September 2005.
45. U.S. Food and Drug Administration. NDA 020831 Formoterol fumarate clinical review. 2005. Accessed at www.fda.gov/ohrms/dockets/ac/05/briefing/ 2005-4148B1_03_03-FDA-Clinical-Review.pdf on 3 September 2005.
46. U.S. Food and Drug Administration. Center for Drug Evaluation and Review. Serevent (Salmeterol Xinafoate inhalation) diskus. Part 2. 2001. Accessed at www.fda.gov/cder/foi/nda/98/20692S1,2_Serevent_medr_P2.pdf on 3 September 2005.
47. U.S. Food and Drug Administration. Serevent Pivotal Safety and Efficacy: SLD-390. 2001. Accessed at www.fda.gov/cder/foi/nda/98/20692S1, 2_Serevent_medr_P1.pdf on 9 December 2005.
48. Von Berg A, Papageorgiou Saxoni F, Wille S, Carrillo T, Kattamis C, Helms PJ. Efficacy and tolerability of formoterol Turbuhaler in children. Int J Clin Pract. 2003;57:852-6.
49. Weinstein SF, Pearlman DS, Bronsky EA, Byrne A, Arledge T, Liddle R, et al. Efficacy of salmeterol xinafoate powder in children with chronic persistent asthma. Ann Allergy Asthma Immunol. 1998;81:51-8.
50. Arledge TE, Liddle R, Stahl E, Rossing TH. Salmeterol does not cause tolerance during long-term asthma therapy. J Allergy Clin Immunol. 1996;98:1116-9.
51. Bijl-Hofland ID, Cloosterman SG, Folgering HT, van den Elshout FJ, van Weel C, van Schayck CP. Inhaled corticosteroids, combined with long-acting beta(2)-agonists, improve the perception of bronchoconstriction in asthma. Am J Respir Crit Care Med. 2001;164:764-9.
52. Boyd G. Salmeterol xinafoate in asthmatic patients under consideration for maintenance oral corticosteroid therapy. UK Study Group. Eur Respir J. 1995;8:1494-8.
53. Busse WW, Casale TB, Murray JJ, Petrocella V, Cox F, Rickard K. Efficacy, safety, and impact on quality of life of salmeterol in patients with moderate persistent asthma. Am J Manag Care. 1998;4:1579-87.
54. Chervinsky P. Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator. J Allergy Clin Immunol. 1977;59:22-30.
55. Cloosterman SG, Bijl-Hofland ID, van Herwaarden CL, Akkermans RP, van Den Elshout FJ, Folgering HT, et al. A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic asthmatic patients. Chest. 2001;119:1306-15.
56. Creticos PS, Freidhoff LR, Bernstein DI, Chu T, Khattignavong AP, Pasatiempo AM, et al. Comparison of an inhaled corticosteroid (triamcinolone acetonide) to a long-acting bronchodilator (salmeterol), the combination, and placebo in mild-moderate adult asthmatic patients. Int Arch Allergy Immunol. 1999;118:345-6.
57. Deykin A, Lazarus SC, Fahy JV, Wechsler ME, Boushey HA, Chinchilli VM, et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol. 2005;115:720-7.
58. Ekstrom T, Ringdal N, Tukiainen P, Runnerstrom E, Soliman S. A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo-controlled study. Ann Allergy Asthma Immunol. 1998;81:225-30.
59. Ekstrom T, Ringdal N, Sobradillo V, Runnerstrom E, Soliman S. Low-dose formoterol Turbuhaler (Oxis) b.i.d., a 3-month placebo-controlled comparison with terbutaline (q.i.d.). Respir Med. 1998;92:1040-5.
60. FitzGerald JM, Chapman KR, Della Cioppa G, Stubbing D, Fairbarn MS, Till MD, et al. Sustained bronchoprotection, bronchodilatation, 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;103:427-35.
61. Kavuru M, Melamed J, Gross G, Laforce C, House K, Prillaman B, 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.
62. Kemp JP, DeGraff AC Jr, Pearlman DS, Wang Y, Arledge TE, Welch MB, et al. A 1-year study of salmeterol powder on pulmonary function and hyperresponsiveness to methacholine. J Allergy Clin Immunol. 1999;104:1189-97.
63. LaForce C, Prenner BM, Andriano K, Lavecchia C, Yegen U. Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma. J Asthma. 2005;42:101-6.
64. Li X, Ward C, Thien F, Bish R, Bamford T, Bao X, et al. An antiinflammatory effect of salmeterol, a long-acting beta(2) agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma. Am J Respir Crit Care Med. 1999;160:1493-9.
65. Meijer GG, Postma DS, Mulder PG, van Aalderen WM. Long-term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids. Am J Respir Crit Care Med. 1995;152:1887-92.
66. Nathan RA, Seltzer JM, Kemp JP, Chervinsky P, Alexander WJ, Liddle R, et al. Safety of salmeterol in the maintenance treatment of asthma. Ann Allergy Asthma Immunol. 1995;75:243-8.
67. Nathan RA, Pinnas JL, Schwartz HJ, Grossman J, Yancey SW, Emmett AH, 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.
68. Orsida BE, Ward C, Li X, Bish R, Wilson JW, Thien F, et al. Effect of a long-acting beta2-agonist over three months on airway wall vascular remodeling in asthma. Am J Respir Crit Care Med. 2001;164:117-21.
69. Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol. 1995;75:423-8.
70. Shapiro G, Lumry W, Wolfe J, Given J, White MV, Woodring A, et al. Combined salmeterol 50 microg and fluticasone propionate 250 microg in the diskus device for the treatment of asthma. Am J Respir Crit Care Med. 2000;161:527-34.
71. van der Molen T, Postma DS, Turner MO, Jong BM, Malo JL, Chapman K, et al. Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators. Thorax. 1997;52:535-9.
72. van Schayck CP, Cloosterman SG, Bijl-Hofland ID, van den Hoogen H, Folgering HT, van Weel C. Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2-agonists. Respir Med. 2002;96:155-62.
73. van Schayck CP, Bijl-Hofland ID, Cloosterman SG, Folgering HT, van der Elshout FJ, Van Weel C. Potential masking effect on dyspnoea perception by short- and long-acting beta2-agonists in asthma. Eur Respir J. 2002;19:240-5.
74. von Berg A, de Blic J, la Rosa M, Kaad PH, Moorat A. A comparison of regular salmeterol vs 'as required' salbutamol therapy in asthmatic children. Respir Med. 1998;92:292-9.
75. Wilding P, Clark M, Thompson Coon J, Lewis S, Rushton L, Bennett J, et al. Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study. BMJ. 1997;314:1441-6.
76. Zimmerman B, D'Urzo A, Berube D. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Pediatr Pulmonol. 2004;37:122-7.
77. D'Alonzo GE, Nathan RA, Henochowicz S, Morris RJ, Ratner P, Rennard SI. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994;271:1412-6.
78. Tashkin DP. Is a long-acting inhaled bronchodilator the first agent to use in stable chronic obstructive pulmonary disease? Curr Opin Pulm Med. 2005;11:121-8.
79. Ramsey SD. Suboptimal medical therapy in COPD: exploring the causes and consequences. Chest. 2000;117:33S-7S.
80. Salpeter SR, Buckley NS, Salpeter EE. Meta-analysis: anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD. J Gen Intern Med. 2006; [Forthcoming].
81. van Schayck CP, Graafsma SJ, Visch MB, Dompeling E, van Weel C, van Herwaarden CL. Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol. J Allergy Clin Immunol. 1990;86:793-800.
82. Mcivor RA, Pizzichini E, Turner MO, Hussack P, Hargreave FE, Sears MR. Potential masking effects of salmeterol on airway inflammation in asthma. Am J Respir Crit Care Med. 1998;158:924-30.
83. Hancox RJ, Aldridge RE, Cowan JO, Flannery EM, Herbison GP, McLachlan CR, et al. Tolerance to beta-agonists during acute bronchoconstriction. Eur Respir J. 1999;14:283-7.
84. Hancox RJ, Cowan JO, Flannery EM, Herbison GP, McLachlan CR, Wong CS, et al. Randomised trial of an inhaled beta2 agonist, inhaled corticosteroid and their combination in the treatment of asthma. Thorax. 1999;54:482-7.
85. Kerrebijn KF, van Essen-Zandvliet EE, Neijens HJ. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987;79:653-9.
86. Aldrey OE, Anez H, Deibis L, Tassinari P, Isturiz G, Bianco NE. A double-blind, cross-over study using salbutamol, beclomethasone, and a combination of both in bronchial asthma. J Asthma. 1995;32:21-8.
87. Kalra S, Swystun VA, Bhagat R, Cockcroft DW. Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol. Chest. 1996;109:953-6.
88. Taylor DR, Hancox RJ. Interactions between corticosteroids and beta agonists. Thorax. 2000;55:595-602.
89. Patterns of medication use in the United States 2004. A report from the Slone Survey. Boston: Slone Epidemiology Center at Boston University; 2004. Accessed at www.bu.edu/slone/SloneSurvey/AnnualRpt/SloneSurveyReport2004.pdf on 23 April 2006.
90. The World Factbook. United States. Washington, DC: Central Intelligence Agency; 2005.
91. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Program Description. Bethesda, MD: National Institutes of Health; 2005.
92. Hussey PS, Anderson GF, Osborn R, Feek C, McLaughlin V, Millar J, et al. How does the quality of care compare in five countries? Health Aff (Millwood). 2004;23:89-99.
93. Beasley R, Pearce N, Crane J, Burgess C. Withdrawal of fenoterol and the end of the New Zealand asthma mortality epidemic. Int Arch Allergy Immunol. 1995;107:325-7.
94. Adams NP, Bestall JB, Malouf R, Lasserson TJ, Jones PW. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst Rev. 2005:CD002738.
95. Ernst P, Spitzer WO, Suissa S, Cockcroft D, Habbick B, Horwitz RI, et al. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA. 1992;268:3462-4.
96. Anis AH, Lynd LD, Wang XH, King G, Spinelli JJ, Fitzgerald M, et al. Double trouble: impact of inappropriate use of asthma medication on the use of health care resources. CMAJ. 2001;164:625-31.
97. Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med. 1992;326:501-6.
98. Eisner MD, Lieu TA, Chi F, Capra AM, Mendoza GR, Selby JV, et al. Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma. Eur Respir J. 2001;17:233-40.
99. Lanes SF, Garcia Rodriguez LA, Huerta C. Respiratory medications and risk of asthma death. Thorax. 2002;57:683-6.
100. Clarke PS, Jarrett RG, Hall GJ. The protective effect of ipratropium bromide aerosol against bronchospasm induced by hyperventilation and the inhalation of allergen, methacholine and histamine. Ann Allergy. 1982;48:180-3.
101. Newcomb R, Tashkin DP, Hui KK, Conolly ME, Lee E, Dauphinee B. Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist. Am Rev Respir Dis. 1985;132:12-5.
102. O'Connor BJ, Towse LJ, Barnes PJ. Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1996;154:876-80.
103. Terzano C, Petroianni A, Ricci A, D'Antoni L, Allegra L. Early protective effects of tiotropium bromide in patients with airways hyperresponsiveness. Eur Rev Med Pharmacol Sci. 2004;8:259-64.
104. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005;60:740-6.
105. Westby M, Benson M, Gibson P. Anticholinergic agents for chronic asthma in adults. Cochrane Database Syst Rev. 2004:CD003269.