The Provocholine (methacholine chloride USP) challenge is highly sensitive, and the results are highly accurate. The low incidence of false-negative or false-positive results with Provocholine is due to the specificity of cholinergic stimulation as well as to the precision in preparing reagent dosages. A negative Methacholine Challenge Test rules out asthma with reasonable certainly in patients.
Provocholine is standardized for reliability, with premeasured quantity and consistent quality. The need to weigh out bulk methacholine, a highly hygroscopic agent, is therefore eliminated.
Because of consistent quantity and quality, Provocholine delivers reproducible results.
Starting with a premeasured vial of powder, serial dilutions can be made quickly with sterile normal saline (0.9% sodium chloride for injection) containing 0.4% phenol (pH 7.0 or with sterile normal saline 0.9% sodium chloride for injection). The Provocholine challenge provides rapid results, with FEV1 measurements within five minutes after each challenge concentration. Back To Top
Provocholine® is indicated for the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma. A negative methacholine challenge test excludes airway hyperresponsiveness and can be used to exclude a diagnosis of asthma.
According to the American Thoracic Society Guidelines for Methacholine and Exercise Challenge Guidelines for Methacholine and Exercise Challenge Testing – 1999:
Methacholine challenge testing is most often considered when asthma Methacholine challenge testing is most often considered when asthma is a serious possibility and traditional methods, most notably spirometry performed before and after administration of a bronchodilator, have not established or eliminated the diagnosis. (i.e. post-bronchodilator response was not significant in that the increase in FEV1 or FVC ≤ 12% and ≤ 200 mL).
Methacholine challenge testing is also a valuable tool in the evaluation of occupational asthma. Back To Top
Always consider objective measurements when contemplating an asthma diagnosis. There are several consequences associated with improper treatment such as: under treatment of the disease, potential exposure to inappropriate medications, lost employment opportunities (i.e., military, public services), social consequences and economic factors.
Several studies and abstract presentations have shown that patients with physician diagnosed asthma may have been misdiagnosed in approximately 1/3 of cases, and one study showed as many as 41% of patients had been misdiagnosed. The American Thoracic Society (ATS) Guidelines for Methacholine and Exercise Challenge Testing suggests that even asthma specialists are not able to reliably predict the outcome of the Methacholine Challenge Test. To confirm a diagnosis of asthma, objective testing should be performed. Back To Top
To access the source publication, click the following link to exit our website and be directed to the American Thoracic Society website.
Click Statements>scroll down to 'Pulmonary Function and Exercise Testing' and select 'Guidelines for Methacholine and Exercise Challenge Testing'.
A concern associated with methacholine challenge testing is the safety profile of the test procedure. Challenge testing with methacholine has been performed for well over 30 years. Multiple studies and publications have reviewed the expected protocol for performance, safety, and interpretation of the results. In 1999, the American Thoracic Society (ATS) published a Guideline for Methacholine and Exercise Challenge Testing. This guideline is currently under revision by a group representing both the ATS and European Respiratory Society (ERS).
Early studies published by Townly, et al in 1979, found that in over 1500 patients, there were no initial or delayed severe reactions that required hospitalization. Pratter and colleagues reported similar results in 1984 in over 1000 completed methacholine challenge tests. Another study published in 1993 by Pratter and colleagues reported on issues of safety and bronchodilator reversibility in a prospective study of 62 cases. The mean baseline FEV1 was 2.60 L (93 + 13 percent of predicted). The authors found both bronchospasm and symptoms reversed with administration of albuterol delivered by MDI and a spacer. All patients returned to acceptable baseline levels within 30 minutes of administration of the albuterol. Physician intervention was not required in any of the cases. Their conclusion was that methacholine challenge testing did not need to be confined to the hospital.
In 1997, a study by R. Martin, et al. investigated the safety of methacholine challenge testing in a retrospective analysis of 88 patients with a baseline FEV1 less than 60% (ranging from 22 to 59%) of predicted. Only 4 patients did not return to greater than 90% of the baseline FEV1 following administration of a poststudy beta-agonist treatment. A second post study beta-agonist treatment returned the final four patients to the baseline FEV1. None of the patients suffered any adverse events. An earlier study in 1982 by Ramsdell and colleagues revealed the safety of methacholine challenge testing in markedly obstructed patients. (baseline FEV1 0.45 to 1.66 L)
The Childhood Asthma Management Program (CAMP) evaluated the safety of methacholine provocation testing performed serially over an 11-year period. The baseline FEV1 was greater than 70% of predicted in this study. More than 8000 challenges were performed in children with mild to moderate asthma using a standardized protocol. Only 0.4% of the patients did not return to > 90% of the baseline FEV1.
The Lung Health Study has resulted in large numbers of methacholine challenge tests in patients with mild to moderate airflow obstruction (>5000) These results confirmed the safety of the test procedure in large-scale epidemiologic studies.
Although methacholine challenge testing has been found to be safe even in patients with a lower FEV1, testing should be approached and completed with a standard operating procedure in adherence to the current standards of care. All testing sites should have a standardized approach to testing and the ability to respond quickly and appropriately to adverse events. Back To Top
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