Methacholine Test: Treatment, Effect & Risks

The so-called metacholine test is intended to benefit primarily suspected asthma patients for whom no diagnosis can be confirmed by other means to date. The provocation test is designed to trigger an overreaction of the lungs by inhalation of the drug substance metacholine and to confirm the diagnosis in this way. Because asthma attacks may occur during the course of the test, it should be performed only by trained professionals in a designated laboratory.

What is the metacholine test?

The metacholine test is a provocation test and is usually used when the diagnosis of bronchial asthma cannot be confirmed by other means. The metacholine test is also known as the metacholine provocation test. It is a widely used pharmacological allergy test that is performed by inhalation and is considered to be extremely sensitive, but also relatively non-specific. Like all provocation tests for allergy diagnostics, the metacholine provocation test aims to provoke an irritation to a specific substance. By inhaling a drug, the test thus aims to initiate an overreaction of the lungs. This procedure is usually used when the diagnosis of bronchial asthma cannot be confirmed by other means. For the test, 33 milligrams of methacholine chloride is administered in a solution containing the excipients disodium hydrogen phosphate-2-water and sodium dihydrogen phosphate-1-water, which is thought to induce constriction of the pulmonary apparatus.

Function, effects, and goals

Metacholine tests are used in allergology as well as pulmonology to diagnose bronchial asthma. This form of asthma is caused by a hypersensitive bronchial space that reacts to stimuli with shortness of breath or coughing attacks. The hypersensitivity of the bronchial system is assessed in the metacholine test by inhalation of the drug substance metacholine. Metacholine is a muscarinic receptor agonist. It is a direct parasympathomimetic that causes constriction in the bronchi. In both asthma patients and patients with chronic inflammation, inhalation of the drug triggers a much stronger reaction than would be the case in healthy lungs. Before the test, the physician usually clarifies the medical history and performs a general lung function test. He often also arranges special allergy tests in advance to rule out an allergy as the cause of the patient’s breathing difficulties. Since the respiratory disease COPD also manifests itself as shortness of breath and it is often not possible to differentiate it from asthma in any other way, inhalation tests with drugs such as steroids are also frequently carried out. In asthmatics, these tests lead to a marked improvement in all symptoms, whereas in COPD patients, as a rule, no improvement at all can be expected. After these preliminary examinations and preliminary tests, in most cases, if asthma is suspected, the patient visits a specialized clinical laboratory where the metacholine test is performed. A special device records lung function at rest in advance. This lung function test takes place in a pressure-stable glass cabin and provides information about the general constitution of the bronchial tubes. A number of other respiratory diseases can be ruled out or diagnosed in the course of these recordings. If bronchial asthma is still suspected, the first inhalation of metacholine is then performed to determine a blank value. This inhalation initially takes place via a carrier solution. After this first blank determination, the test may already be completed if the patient has shown extreme reactions. If this is not the case, the blank determination is followed by a stepwise inhalation of metacholine in increasing doses, carried out via nebulizers. After each of the five stages, data are collected and plotted on a dose-response curve. Spirometry is used primarily to monitor airway resistance, changes in which over the course of the test should confirm or rule out the diagnosis.

Risks, side effects, and hazards

The metacholine test is not without danger and is associated with a number of hazards, especially for asthmatics, but these can be well controlled in the laboratory. For example, the metacholine test often triggers an asthma attack. This attack can be of varying severity and requires the presence of trained personnel, which is of course available in the specialized laboratory.For these reasons, however, the test should be performed only and exclusively in the laboratories designated for this purpose with specialized personnel, otherwise the patient is putting his own health at risk. In any specialized laboratory for the evaluation of lung function, the supply of oxygen is guaranteed in the event of breathing difficulties, and emergency physicians are on call to respond. Once the test is complete, the patient is also given an antidote to calm the lungs. Without these controlled conditions, the risks to the patient are too high. Even aside from these high risks and side effects, the test presents some difficulties. Although the provocation procedure is an extremely sensitive test, all people react with constriction of the lungs above a certain dose of metacholine. The mean value for this dosage is about 2.9 milligrams of the drug. Thus, a reaction to inhalation does not necessarily mean that the patient actually suffers from severe asthma. From this point of view, the test lacks specificity despite its high sensitivity, which is often a point of criticism. Apart from the natural constriction from 2.9 milligrams, other bronchial disease can sometimes trigger strong reactions to lower-dose metacholine, making the test even more nonspecific. Nevertheless, bronchial provocation testing is now almost always part of asthma diagnosis.