Paradoxical bronchoconstriction caused by β2-adrenoceptor agonists

  • Khadija Ayed Department of Physiology, Faculty of Medicine of Tunis, University of Tunis el Manar, Tunis - Tunisia
  • Islam Latifa Hadi Khalifa Department of Physiology, Faculty of Medicine of Tunis, University of Tunis el Manar, Tunis - Tunisia
  • Salma Mokaddem Department of Physiology, Faculty of Medicine of Tunis, University of Tunis el Manar, Tunis - Tunisia
  • Saloua Ben Khamsa Jameleddine Department of Physiology, Faculty of Medicine of Tunis, University of Tunis el Manar, Tunis - Tunisia
Keywords: Asthma, Bronchoconstriction, Bronchodilators, β-2 adrenergic agonists, Spirometry


Introduction: Salbutamol and terbutaline are short-acting β2 adrenergic agonists that produce bronchial smooth muscle relaxation and are widely used in obstructive pulmonary diseases. Nevertheless, their use has been the cause of a paradoxical bronchoconstriction, which is a rare and potentially serious adverse reaction. The aim of this study is to report a case of paradoxical bronchoconstriction caused by β2 adrenergic agonists.

Methods: This case is about a 50-year-old asthmatic patient who describes a history of repeated acute asthma attacks after salbutamol inhalation or terbutaline nebulization. A double-blind crossover study was performed over 3 days, in order to compare the effects of each bronchodilator. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal expiratory flow 25-75 (MEF25-75) were measured.

Results: On the first day, a bronchoconstriction caused by deep and repeated inhalations was eliminated. On the second day, an airway obstruction was confirmed by a decrease in FEV1 at 40% from baseline values after nebulization of a standard dose of terbutaline. On the third day, a spirometry was performed before and after nebulization of a standard dose of ipratropium bromide, and there were no significant changes in the spirometric parameters. Finally the patient was discharged with a written warning mentioning the danger of salbutamol and terbutaline use.

Conclusion: Salbutamol and terbutaline are generally well-tolerated β2 adrenergic agonists. Nevertheless, in rare cases, these substances can cause a paradoxical bronchoconstriction. Doctors must therefore remain vigilant about its side effect and possibly investigate each case.


Spooner LM, Olin JL. Paradoxical bronchoconstriction with albuterol administered by metered-dose inhaler and nebulizer solution. Ann Pharmacother. Nov 2005;39(11):1924-1927.

Johnson M. Beta2-adrenoceptors: mechanisms of action of beta2-agonists. Paediatr Respir Rev. Mar 2001;2(1):57-62.

Jacobson GA, Hostrup M. Terbutaline: level the playing field for inhaled β2-agonists by introducing a dosing and urine threshold. Br J Sports Med. 26 Jul 2016;bjsports-2016-096453.

Matthew N, Octavio A, Ricardo MF, Ian S. Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why? Arch Dis Child Educ Pract. Dec 2014;2015(100):215-222.

Barisione G, Baroffio M, Crimi E, Brusasco V. Beta-adrenergic agonists. Pharmaceuticals. 30 Mar 2010;3(4):1016-1044.

Williams C, Crossland L, Finnerty J, et al. Case-control study of salmeterol and near-fatal attacks of asthma. Thorax. 1998;53(1):7-13.

Gallelli L. Retrospective analysis of adverse drug reactions to bronchodilators observed in two pulmonary divisions of Catanzaro, Italy. Pharmacol Res. June 2003;47(6):493-499.

Stocks J, Quanjer PH. Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of The European Respiratory Society. Eur Respir J. 1995;8:492-506.

Haynes JM. Bronchoconstriction in response to deep inhalation during spirometry testing. Respir Care. 1 May 2015;60(5):e105-e109.

Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain Behav Immun. 2007;21(8):993-999.

Beasley CR, Rafferty P, Holgate ST. Bronchoconstrictor properties of preservatives in ipratropium bromide (Atrovent) nebuliser solution. Br Med J Clin Res Ed. 1987;294(6581):1197.

George M, Joshi SV, Concepcion E, Lee H. Paradoxical bronchospasm from benzalkonium chloride (BAC) preservative in albuterol nebulizer solution in a patient with acute severe asthma. A case report and literature review of airway effects of BAC. Respir Med Case Rep. 2017;21:39-41.

Findlay SR, Dvorak AM, Kagey-Sobotka A, Lichtenstein LM. Hyperosmolar triggering of histamine release from human basophils. J Clin Invest. 1981;67(6):1604.

Stellato C, de Crescenzo G, Patella V, Mastronardi P, Mazzarella B, Marone G. Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release. J Allergy Clin Immunol. 1996;97(3):838-850.

Schoeffel RE, Anderson SD, Altounyan RE. Bronchial hyperreactivity in response to inhalation of ultrasonically nebulised solutions of distilled water and saline. Br Med J Clin Res Ed. 1981;283(6302):1285-1287.

How to Cite
Ayed K, Hadi Khalifa I, Mokaddem S, Ben Khamsa Jameleddine S. Paradoxical bronchoconstriction caused by β2-adrenoceptor agonists. DTI [Internet]. 5Oct.2020 [cited 20Jan.2021];14(1):12-5. Available from:
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