Diagnostic Bronchoconstrictor Agent
for the Diagnosis of Bronchial Airway Hyperreactivity

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Bronchoprovocation challenge testing with methacholine chloride is:

checkmarkSensitive

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.

checkmarkReliable

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.

checkmarkReproducible

Because of consistent quantity and quality, Provocholine delivers reproducible results.

checkmarkRapid 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

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About Methacholine Challenge Testing

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


When to Consider MCT?

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

Figure2 MCT-Flow-Chart-ATS-Guidelines-1999-nc-bw Figure 2. Methacholine challenge testing sequence (flow chart).
*The choice of the FEV1 value considered a contraindication may vary from 60 to 70% of predicted.
**The final dose may vary depending on the dosing schedule used. Final doses discussed in this statement are 16, 25, and 32 mg/ml.

Clinical Process for MCT

  1. If a patient presents with reoccurring symptoms of airflow obstruction a detailed medical history should be taken along with a physical examination of the upper respiratory tract, chest and skin.1
  2. Spirometry should be performed for every patient (greater than 5 years of age) to determine whether any airway obstruction present is at least partially reversible.1
  3. In patients that have a median probability of asthma the results of the MCT cannot accurately be predicted, even by asthma specialists. If baseline spirometry shows limited airflow obstruction and an insignificant response to a bronchodilator (<12% and <0.2-L in FEV1 or FVC), these patients should be sent for further testing to rule out asthma as the diagnosis.2
  4. The MCT can effectively rule out asthma with greater than 90% certainty, with consideration of the following; ensure that airway responsiveness was not suppressed by intensive anti-inflammatory medications, patient has current symptoms and a small percentage of workers with occupational asthma may react only to a single antigen or chemical sensitizer. The best possible diagnostic value of the MCT occurs when the pretest probability is in the range of 30 to 70 percent.2

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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'.

  1. National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma 2007. Bethesda, Md: National Institutes of Health; August 2007. NIH Publication 07-4051.
  2. ATS Guidelines for Methacholine and Exercise Challenge Testing - 1999 Am J Respir Crit Care Med 2000;161:309-329.
  3. Irvin C. Bronchial challenge: Just do it! Resp Care 2003; 48:589-590.
  4. Aaron, S.D., et al. Overdiagnosis of Asthma in Obese and Nonobese Adults, CMAJ 2008;179:1121-1131.

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Bronchial Provocation with Methacholine

A Literature Review of Safety- Susan Blonshine, TechEd Consultants Inc.

PDF version

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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References

  1. Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and exercise challenge testing. Am J Resp Crit Care Med 200; 161(1):309-329.
  2. Wanger, JS, Ikle DN, Irvin CG. Airway responses to a diluent used in the methacholine challenge test. Ann Allergy Asthma Immunol 2001;86:277-282.
  3. Martin RJ, Wanger JS, Irvin CG, et al. Methacholine challenge testing; safety of low starting FEV1. Chest 1997;112:53-56.
  4. Ramsdell JW, Nachtwey F, Moser KM. Bronchial hyperreactivity in chronic obstructive bronchitis. Am Rev Respir Dis 1982; 126:829-32.
  5. ATS Pulmonary Function Laboratory Management and Procedure Manual. Chapter 12. 2005.
  6. Goldstein, MF, Pacana SM, Dvorin DJ, et al. Retrospective analyses of methacholine inhalation challenges. Chest 1994; 105:1082-88.
  7. Pratter, MR, Irwin RS. Usefulness and safety of pharmacologic Bronchoprovocation challenge in evaluating patients with normal spirometric tests who are suspected of having asthma. Chest 1988; 93:898-900.
  8. Townley RG, Bewtra AK, Nair NM, et al. Methacholine inhalation challenge studies. J Allergy Clin Immunol 1979; 64:569-74.
  9. Pratter, MR, Irwin RS. The clinical value of pharmacologic bronchoprovocation challenge. Chest 1984; 85:260-65.
  10. Pratter MR, Bartter TC, Dubois J. Bronchodilator reversal of bronchospasm and symptoms incurred during methacholine Bronchoprovocation challenge. Documentation of safety and time course. Chest 1993;104:1342-1345.
  11. Tashkin, DP, Altose MD, Bleecker, ER, et al. The Lung Health Study: Airway responsivemess to inhaled methacholine in smokers with mild to moderate airfl ow limitation. Am Rev Respir Dis 1992; 145:301-310.
  12. Tashkin, DP, Altose MD, Connett JE, et al. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. Am Rev Respir Dis 1996;153:1802-11.