Methacholine: what it is, its characteristics and how it is used in the asthma test

Asthma is a respiratory problem that is not always obvious. This can happen when particles and pollutants that activate the asthmatic response travel through the air, and sometimes these particles are not that common.

However, given the severity of this condition, if it appears, the person may have a serious problem. For this reason, it has become necessary to create specific tests to most accurately confirm any case of asthma, and the methacholine test is one of them.

Methacholine is a bronchoconstrictor ideal for generating an asthmatic response in people with the most masked disease. Let us see below what are the properties of this substance and how the test which bears its name is carried out.

    What is methacholine

    Methacholine is a bronchoconstrictor agent used in the diagnosis of asthma, especially the main symptom of this medical condition: Bronchial hyperreactivity. It has its own test, called a methacholine test, and is indicated when other lung function tests, such as generic spirometry, do not suggest a definitive diagnosis. This substance, when aspirated, produces miosis.

    It is a hill ester type non-selective synthetic cholinergic. It works by binding and activating muscarinic acetylcholine receptors in the parasympathetic nervous system. Being very selective, this substance strongly activates all muscarinic receptors and has a very limited effect on nicotinic receptors.


    Methacholine is a quaternary amine which is insoluble across the cell membrane. That is why it cannot cross the blood-brain barrier or be absorbed from the gastrointestinal tract. Once inside the body, this substance is metabolized slowly because it is very resistant to the action of the enzyme acetylcholinesterase.

    It hydrolyses at a very slow rate, slower than the rate at which acetylcholine is hydrolyzed. This is why its action in the organism is more prolonged and almost completely resists hydrolysis by hill esterases or non-specific butyrylcholinesterases.


    Methacholine is used as the main test to confirm the suspicion of asthma. The test in which methacholine is used is called a nonspecific bronchial challenge test or methacholine test. which is used primarily to determine the existence of bronchial hyperresponsiveness, considered the main symptom of asthma.

    This is the abnormal sensitization of the airways, caused by an increase in airway obstruction after coming into contact with specific stimuli.

    What is the methacholine test for asthma?

    The methacholine test consists of doing, first of all, an initial spirometry which will be accompanied by other spirometry, In order to check the patient’s lung capacity and see how it affects the inhalation of methacholine at different doses. Methacholine is a drug with bronchoconstrictor action in people with asthma, that is, it narrows their bronchi when they inhale this substance, reducing their lung capacity for a limited time.

    Initial spirometry measures a person’s basic lung capacity. The patient takes a deep, deep breath, filling his lungs with as much air as possible. Then the filter is placed between his lips, exhaling, that is, blowing with all its forces the air contained for at least six seconds. This process will be repeated at least three times.

    When you have a clear idea of ​​the patient’s lung capacity, methacholine will be administered. in increasing doses, and after each dose a new spirometry will be performed.

    If the patient has a decrease in lung capacity greater than 20% compared to the initial spirometry, the positive test for methacholine will be considered. In other words, it would mean that the patient is reacting to this substance, showing bronchoconstriction and briefly losing their lung capacity. The lower the dose required to lower by more than 20%, the greater the degree of bronchial reaction of the patient.. The diagnosis of asthma will be confirmed.

    On very rare occasions, a person with asthma will test negative for methacholine. Although in many cases asthma is obvious, some are not so clearly, which is why this test is so necessary, ensuring the diagnosis. There are people with asthma who may have had a very normal initial spirometry, without breathing problems of any kind, and with normal bronchodilation without medication.

    This test is minimally invasive and is generally well tolerated by the patient., Who will hardly feel any discomfort. The only minimally significant discomfort is the time required to perform the test and the need to do several spirometry tests which require a little pulmonary effort.

    Requirements to be able to apply the test

    In order to apply this test, the patient must comply with a series of requirements and guidelines before going to the appointment with the pulmonologist. The patient should indicate if he or she has had any signs of asthma or a respiratory infection in the past 6 or 8 weeks., In addition to reporting if, in the past two months, he has been immunized with vaccines. It is necessary to report a possible pregnancy, heart disease or if you have had hives recently.

    The patient should have avoided consuming the following substances during the following periods:

    • Caffeinated drinks (coffee and tea): duration 6 hours.
    • Tobacco: do not smoke the day before the test.
    • Inhaled bronchodilators: last 12 hours.
    • Parenteral bronchodilators: last 12 hours.
    • Short-acting oral bronchodilators: 18 hours.
    • Long-acting oral bronchodilators: last 48 hours.

    Contraindications, warnings and precautions

    The main precaution to be taken with the methacholine test is that it is performed under the supervision of a specialist doctor, Have emergency supplies and medicines to avoid unforeseen events. The risks and benefits of applying the test in epilepsy, cardiovascular disease with bradycardia, vagotonia, peptic ulcer disease, urinary tract obstruction or other conditions which may be affected by a cholinergic agent should be evaluated.

    There are several medical conditions in which the use of methacholine, along with other muscarinic agonists, is contraindicated. Among them we find coronary heart disease, peptic ulcers, myocardial infarction, uncontrolled hypertension, Myasthenia gravis and urinary incontinence. This is because the similar action of this substance to that of the parasympathetic system can worsen the symptoms of these medical problems.

    Its use is also not recommended in clinically apparent asthma or in cases of hypersensitivity to other parasympathomimetic agents. It should not be used as part of treatment with beta blockers or cholinesterase inhibitors. Treatment of asthma and hay fever inhibits the response of the airways to the test.

    Application of this test can give false positives in diseases such as influenza, respiratory tract infections, very young or old patients, chronic lung disease, allergic rhinitis without asthma, smokers or those who were exposed to air pollutants. In these cases, in addition to being able to have false positive asthma, there is a risk of severe bronchoconstriction and a highly dangerous reduction in respiratory function.

    If the patient is a woman and is of childbearing age, it is necessary to find out whether she is pregnant. No studies have been performed on teratogenic effects. of methacholine on animal reproduction. It is not known whether methacholine hydrochloride can harm the fetus or if it can affect a patient’s fertility. It should only be administered to pregnant women if its application is clearly necessary. It is not known whether methacholine, when inhaled, is excreted in human milk.

    Adverse reactions and interactions

    among the main side effects of methacholine we can find headache, pharyngeal irritation, feeling of loss of consciousness and itching (Tingling sensation on the skin). The therapeutic use of this drug is limited due to its cardiac side effects, such as bradycardia and hypotension, which is doubled due to its function as a cholinergic agonist. Methacholine reacts very toxic in association with 0.5 to 1 mg of atropine sulfate intramuscularly or intravenously.

    Bibliographical references:

    • Katzung, Bertram G. (2004). Basic and clinical pharmacology (9th edition). ISBN 0-07-141092-9.
    • Lötvall J, Inman M, O’Byrne P (1998). Measurement of airway hyperresponsiveness: new considerations. Thorax 53: 419-424. PMID 9708238.
    • R. Asero, E. Madonini. (2006) Bronchial hyperresponsiveness is a common feature in patients with chronic urticaria. J Investig Allergol Clin Immunol; Flight. 16 (1): 19-23.

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