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When should a methacholine challenge be ordered for a patient with suspected asthma?

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The methacholine challenge test isused in several situations:

If the diagnosis of asthma is in question, eg, if the patient has symptoms that suggest asthma (either typical symptoms such as coughing, wheezing, and dyspnea or atypical symptoms) but normal results on regular spirometric testing and no response to a bronchodilator. Because the test has a high negative predictive value, it is more useful in ruling out asthma (if the result is negative) than in ruling it in (if the result is positive).1,2 A negative methacholine challenge test nearly rules out asthma; however, a positive test result needs to be interpreted cautiously if the patient is not experiencing symptoms.

In establishing a diagnosis of occupational asthma. For patients with remitting and relapsing symptoms suggestive of asthma associated with a particular work environment, a detailed history, physical examination, and methacholine challenge test can establish the diagnosis. Specific bronchial challenge testing with the suspected offending agent is possible, although this is more frequently used in research and in situations with significant legal or financial implications for the patient, such as workers’ compensation cases.3

Possibly, in managing asthma. In several clinical trials,4,5 outcomes were better when asthma management decisions were based on airway hyper responsiveness combined with conventional factors (symptoms and lung function) than with management based on conventional factors alone. These findings suggest that asthma management based on serial measurement of airway hyperresponsiveness may be useful in optimizing outcomes of care; however, adjustment in treatment according to response to serial methacholine challenge tests is currently not recommended for routine management of asthma.

In clinical research.


Asthma is a chronic inflammatory disorder of the airways associated with characteristic clinical symptoms of wheezing, chest tightness, breathlessness, and cough. These symptoms may be associated with airflow limitation that is at least partially reversible, either spontaneously or with treatment.

Spirometry can confirm the diagnosis of asthma if lung function improves after a bronchodilator is given, as reflected by an increase in forced expiratory volume in 1 second (FEV1) of more than 12% and more than 0.2 L.6,7

Conversely, during bronchoprovocation testing, airflow obstruction is provoked by a stimulus known to elicit airway narrowing, such as inhaled methacholine. Bronchial hyperresponsiveness can reliably distinguish patients with asthma from those without asthma.


During the test, the patient inhales methacholine aerosols in increasing concentrations; various protocols can be used. Spirometry is performed before and after each dose, and the results are reported as a percent decrease in FEV1 from baseline for each step of the protocol.

A positive reaction is a 20% fall in FEV1, and the provocative concentration that causes a positive reaction (the PC20) is used to indicate the level of airway hyperresponsiveness. If the FEV1 does not fall by at least 20% with the highest concentration of methacholine, the testis interpreted as negative and the PC20 is reported as “more than 16 mg/mL” or “more than 25 mg/mL,” depending on the highest dose given.

The maximum dose of methacholine varies among pulmonary function testing laboratories and asthma specialists; final doses of 16, 25, and 32 mg/mL are commonly used. Studies have defined a range of 8 to 16 mg/mL as an optimal cutoff point to separate patients with asthma from those without asthma.2,6,7

The response to methacholine can also be expressed in terms of specific airway conductance;however, this is more complicated and requires body plethysmography.

Other stimuli that can be used as bronchoprovocation challenges to diagnose asthma include inhaled histamine, exposure to cold air, or eucapneic hyperventilation.Compared with these alternative stimuli, methacholine is the most feasible as it does not require extensive equipment and is better tolerated than histamine.8

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