ReviewDrug safety1994
The beta 2-agonist controversy. Observations, explanations and relationship to asthma epidemiology.
Review in Drug safety, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Canadian Asthma Consensus Report, 1999. Canadian Asthma Consensus Group.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 1999Guideline
- Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.The Journal of allergy and clinical immunology · 2019Trial
- Cost effectiveness of fluticasone propionate and flunisolide in the treatment of corticosteroid-naive patients with moderate asthma.PharmacoEconomics · 1999Trial
- Trial
- Trial
- The Changing Asthma Management Landscape and Need for Appropriate SABA Prescription.Advances in therapy · 2023Article
- Identification and Characterization of Novel Bronchodilator Agonists Acting at Human Airway Smooth Muscle Cell TAS2R5.ACS pharmacology & translational science · 2020Article
- Taste and smell GPCRs in the lung: Evidence for a previously unrecognized widespread chemosensory system.Cellular signalling · 2018Review
- Coupling of Airway Smooth Muscle Bitter Taste Receptors to Intracellular Signaling and Relaxation Is via GAmerican journal of respiratory cell and molecular biology · 2017Article
- A Heterotopic Xenograft Model of Human Airways for Investigating Fibrosis in Asthma.American journal of respiratory cell and molecular biology · 2017Article
- Article
- Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2014Article
- Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma.Transactions of the American Clinical and Climatological Association · 2014Article
- Severe refractory asthma: an update.European respiratory review : an official journal of the European Respiratory Society · 2013Review
- Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators.Expert opinion on therapeutic targets · 2013Review
- TAS2R activation promotes airway smooth muscle relaxation despite β(2)-adrenergic receptor tachyphylaxis.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- Pattern of asthma medication use among children from a large urban center in Brazil.European journal of clinical pharmacology · 2012Article
- Enhancement of inflammatory mediator release by beta(2)-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action.British journal of pharmacology · 2010Article
- A Holy Grail of asthma management: toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids.British journal of pharmacology · 2008Review
- ADRB2 Arg16Gly polymorphism, lung function, and mortality: results from the Atherosclerosis Risk in Communities study.PloS one · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Links between frequent use of inhaled beta 2-agonists and morbidity and mortality from asthma appear probable. Two mortality epidemics followed the marketing of potent inhaled adrenergic agents. Case-control studies in New Zealand linked mortality with prescription of fenoterol, especially in severe asthma. A Saskatchewan case-control study confirmed an association of mortality with fenoterol, and also with frequent use of salbutamol (albuterol). Cardiac effects of beta 2-agonists do not cause mortality, but frequent use of these agents may increase the chronic severity of asthma, hence increasing the number of asthmatic patients at risk of death in an acute attack. Frequent use of beta 2-agonists may reduce lung function, increasing airway responsiveness, and impair control of asthma, despite use of inhaled corticosteroids. Mechanisms for this effect may include tachyphylaxis to nonbronchodilator effects, increased responsiveness to allergen, interaction with corticosteroid receptors, altered mucociliary function, differential effects of enantiomers, and masking of symptoms by beta 2-agonist use. The withdrawal of fenoterol from New Zealand in 1990 was associated with a substantial decline in morbidity and mortality. Overall, the evidence suggests that frequent use of inhaled beta 2-agonists has a deleterious effect on the control of asthma. Epidemics of mortality are explained by an increase in chronic severity of asthma following introduction of more potent beta 2-agonists. While beta 2-agonists remain essential for relief of breakthrough symptoms, long term use, particularly with high doses of potent agents, appears to be detrimental.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.