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. 2004;2004(3):CD003269.
doi: 10.1002/14651858.CD003269.pub2.

Anticholinergic agents for chronic asthma in adults

M Westby  1 , M Benson, P Gibson
Affiliations

Anticholinergic agents for chronic asthma in adults

M Westby et al. Cochrane Database Syst Rev. 2004.

Abstract

Background: Anticholinergic agents such as ipratropium bromide are sometimes used in the treatment of chronic asthma. They effect bronchodilation and have also been used in combination with beta2-agonists in the management of chronic asthma.

Objectives: To examine the effectiveness of anticholinergic agents versus placebo and in comparison with beta2-agonists or as adjunctive therapy to beta2-agonists.

Search strategy: The Cochrane Airways Group asthma and wheeze database was searched with a pre-defined search strategy. Searches were current as of August 2003. Reference lists of articles were also examined.

Selection criteria: Randomised trials or quasi-randomised trials were considered for inclusion. Studies assessing an anticholinergic agent versus placebo or in combination/comparison with beta2-agonists were included. In practice, all beta2-agonists were short acting. Short-term (less than 24 hours duration) and longer-term studies were separated; the latter are reported in this review and the former in the review, "Anticholinergic agents for chronic asthma in adults short term".

Data collection and analysis: Two reviewers independently assessed abstracts for retrieval of full text articles. Papers were then assessed for suitability for inclusion in the review. Data from included studies were extracted by two reviewers and entered into the software package (RevMan 4.2). We contacted authors for missing data and some responded. Adverse effect data were analysed if reported in the included studies.

Main results: The studies analysed were in two groups: those comparing anticholinergics with placebo and those comparing the combination of anticholinergics with short acting beta2-agonists versus short acting beta2-agonists alone. The former group had 13 studies involving 205 participants included in this review, and the latter 9 studies involving 440 patients. Generally methodological quality was poorly reported, and there were some reservations with respect to the quality of the studies. Despite the limited number of studies that could be combined, anticholinergic agents in comparison with placebo resulted in more favourable symptom scores particularly in respect of daytime dyspnoea (WMD -0.09 (95%CI -0.14, -0.04, 3 studies, 59 patients). Daily peak flow measurements also showed a statistically significant improvement for the anticholinergic (e.g. morning PEF: WMD =14.38 litres/min (95%CI 7.69, 21.08; 3 studies, 59 patients). However the clinical significance is small and in terms of peak flow measurements equates to approximately a 7% increase over placebo. The more clinically relevant comparison of a combination of anticholinergic plus short acting beta2-agonist versus short acting beta2-agonist alone gave no evidence in respect of symptom scores or peak flow rates of any significant differences between the two regimes. Again there are reservations with respect to the quality of the information from which these conclusions are drawn.

Reviewers' conclusions: Overall this review provides no justification for routinely introducing anticholinergics as part of add-on treatment for patients whose asthma is not well controlled on standard therapies. This does not exclude the possibility that there may be a sub-group of patients who derive some benefit and a trial of treatment in individual patients may still be justified. The role of long term anticholinergics such as tiotropium bromide has yet to be established in patients with asthma and any future trials might draw on the messages derived from this review.

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Conflict of interest statement

None known.

Figures

1
1
Fig 1 Study flow.
1.1
1.1. Analysis
Comparison 1 Longer term AC+BA vs BA, Outcome 1 Withdrawals due to treatment failure/side effects.
1.2
1.2. Analysis
Comparison 1 Longer term AC+BA vs BA, Outcome 2 No of patients with side effects.
2.1
2.1. Analysis
Comparison 2 Longer Term AC vs placebo, Outcome 1 Symptom score paired mean difference (Scale ‐1 to +1).
2.2
2.2. Analysis
Comparison 2 Longer Term AC vs placebo, Outcome 2 PEF paired analysis (scale ‐100 to +100 l/min).
2.3
2.3. Analysis
Comparison 2 Longer Term AC vs placebo, Outcome 3 Patient preference.
2.4
2.4. Analysis
Comparison 2 Longer Term AC vs placebo, Outcome 4 Number of patients dropping out.
2.5
2.5. Analysis
Comparison 2 Longer Term AC vs placebo, Outcome 5 Adverse effects ‐ number of patients.
3.1
3.1. Analysis
Comparison 3 IB 40 vs IB 80, Outcome 1 Symptom score (scale ‐4 to +4).
3.2
3.2. Analysis
Comparison 3 IB 40 vs IB 80, Outcome 2 PEF (scale ‐100 to +100 l/min).
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Dutt 1990 {published data only}
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Elwood 1982 {published data only}
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Fischbacher 1984 {published data only}
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Flint 1983a {published data only}
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Flint 1983b {published data only}
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Foster 1983 {published data only}
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Frith 1987 {published data only}
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Gaba 1987 {published data only}
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Gillies 1987 {published data only}
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Ginesu 1983 {published data only}
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Gotz 1983 {published data only}
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Gross 1975a {published data only}
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Gross 1975b {published data only}
    1. Gross HJ. Dose‐response study of the effect of Sch 1000 MDI on forced vital capacity (FVC), FEV1.0, maximal mid‐expiratory flow (MMEF) and heart rate, ECG. Postgraduate Medical Journal 1975;51(Suppl 7):95.
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Gutersohn 1975 {published data only}
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Huhti 1986 {published data only}
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Irsigler 1975 {published data only}
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Jenkins 1981 {published data only}
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Jindal 1989 {published data only}
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Johnson 1989 {published data only}
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Jolobe 1981 {published data only}
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Kaik 1975 {published data only}
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Kaik 1976 {published data only}
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Kaik 1979 {published data only}
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Kamburoff 1975 {published data only}
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Kaptein 1993 {published data only}
    1. Kaptein AA, Brand PL, Dekker FW, Kerstjens HA, Postma DS, Sluiter HJ. Quality‐of‐life in a long‐term multicentre trial in chronic nonspecific lung disease: Assessment at baseline. European Respiratory Journal 1993;6:1479. - PubMed
Kennedy 1964 {published data only}
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Kerstjens 1992 {published data only}
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Kerstjens 1993a {published data only}
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Kerstjens 1993b {published data only}
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Kerstjens 1994 {published data only}
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Kerstjens 1995 {published data only}
    1. Kerstjens HA, Schouten JP, Brand PLP, Schoonbrood DF, Sterk PJ, Postma DS, et al. Importance of total serum IgE for improvement in airways hyperresponsiveness with inhaled corticosteroids in asthma and chronic obstructive. American Journal of Respiratory & Critical Care Medicine 1995;151:360. - PubMed
Kok‐Jensen 1979 {published data only}
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Kradjan 1992 {published data only}
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Kreisman 1984 {published data only}
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Krivoy 1987 {published data only}
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Kunkel 1976 {published data only}
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Kunkel 2000 {published data only}
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Lahdensuo 1975 {published data only}
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Laitinen 1986 {published data only}
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Lanser 1975 {published data only}
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Larsson 1987 {published data only}
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Lavandier 1987 {published data only}
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Lawford 1983 {published data only}
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Lefcoe 1982 {published data only}
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Lehrer 1993 {published data only}
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Lichterfeld 1979 {published data only}
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Linehan 1975 {published data only}
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Maesen 1975a {published data only}
    1. Maesen F, Buytendijk HJ. Dose‐ and time‐response curves of Sch 1000 MDI and placebo. Differential response in asthmatics and bronchitics as neasured by FEV1.0, vital. Postgraduate Medical Journal 1975;51(Suppl 7):97.
Maesen 1975b {published data only}
    1. Maesen FP. Comparison of the effects of Sch 1000 MDI and fenoterol MDI in patients with bronchial asthma and chronic bronchitis. Postgraduate Medical Journal 1975;51(Suppl 7):116.
Maesen 1982 {published data only}
    1. Maesen FP, Smeets JJ, Rubingh G. Vergelijking van het bronchospasmolytisch effect van druk‐aerosolen met fenoterol (Berotec) en van een combinatie van fenoterol en een. Tijdschrift voor geneeskunde 1982;7:1184.
Maesen 1985 {published data only}
    1. Maesen FP, Smeets JJ, Pover GM. Comparison of the effects of a combination inhaler containing salbutamol and atropine methonitrate By comparison with each component given. Tijdschrift voor Therapie Geneesmiddel en Onderzoek 1985;10:1000.
Mann 1984 {published data only}
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Marcatili 1984 {published data only}
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Marin 1987 {published data only}
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Marlin 1978 {published data only}
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Mattila 1966 {published data only}
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McIntosh 1986a {published data only}
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McIntosh 1986b {published data only}
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Petrie 1975a {published data only}
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Petrie 1975b {published data only}
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Pounsford 1983 {published data only}
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Rafferty 1987 {published data only}
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Rebuck 1979 {published data only}
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Ruffin 1977 {published data only}
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Ruffin 1987b {published data only}
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Sahlstrom 1986 {published data only}
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Speirs 1987 {published data only}
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Stewart 1987 {published data only}
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Storms 1975a {published data only}
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Storms 1975b {published data only}
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Stresemann 1975 {published data only}
    1. Stresemann E. Time‐response curves of Sch 1000 and isoprenaline as metered dose inhalers (MDI) as assessed by measurements of total airways resistance (Rt). Postgraduate Medical Journal 1975;51(Suppl 7):119.
Stresemann 1976a {published data only}
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Stresemann1976b {published data only}
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Tang 1984 {published data only}
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Tarlo 1982 {published data only}
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Taube 2002 {published data only}
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Thiessen 1979 {published data only}
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Trinquet 1975 {published data only}
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Tukiainen 1985 {published data only}
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Uffholtz 1975 {published data only}
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Ullah 1980 {published data only}
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Ullah 1981 {published data only}
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Ulmer 1979 {published data only}
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Vakil 1985 {published data only}
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Verstraeten 1974a {published data only}
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Verstraeten 1974b {published data only}
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Verstraeten 1975 {published data only}
    1. Verstraeten JM. Bronchial response of asthmatic and bronchitic patients to fenoterol MI with or without subsequent Sch 1000 MDI. Postgraduate Medical Journal 1975;51(Suppl 7):120.
Villate 1980 {published data only}
    1. Villate Navarro JI, Sobradillo Pena V, Atxotequi Iaraoligoitia V, Salaverri Nalda A, Orive Martinez C. [Comparative effects of terbutaline sulphate and ipratropium bromide on the respiratory system]. Medecine Clinique et Experimentale 1980;74:275. - PubMed
Vlagopoulos 1975 {published data only}
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Vlagopoulos 1976 {published data only}
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Vogt 1974 {published data only}
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Walker 1987 {published data only}
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Ward 1987 {published data only}
    1. Ward MJ, MacFarlane JT, Davies D. Anticholinergics in severe asthma. Postgraduate Medical Journal 1987;63(Suppl 1):2.
Watson 1992 {published data only}
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Wegener 1987a {published data only}
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Wegener 1987b {published data only}
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Wempe 1992 {published data only}
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Wesolowski 1985 {published data only}
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Wildbolz 1977 {published data only}
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Wilson 1978 {published data only}
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Windom 1990 {published data only}
    1. Windom HH, Burgess CD, Siebers RW, Purdie G, Pearce N, Crane J, Beasley R. The pulmonary and extrapulmonary effects of inhaled beta‐agonists in patients with asthma. Clinical Pharmacology and Therapeutics 1990;48:296. - PubMed
Yanai 1991 {published data only}
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Yang 1989 {published data only}
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Yeager 1976 {published data only}
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Zanen 1995 {published data only}
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Zaritsky 1999 {published data only}
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Zuck 1987 {published data only}
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