METHACHOLINE CHALLENGE TESTING

Methacholine Challenge Testing

Methacholine Challenge Testing

Introduction

The diagnosis of asthma is usually made after careful consideration of a patient's individual history and the demonstration of reversible airway obstruction. Those are the easy ones. For many patients with some combination of cough, wheezing, dyspnea, and chest tightness, the diagnosis may remain unclear after initial history, physical examination, and spirometry. In such cases, the methacholine challenge test (MCT) has become the most widely used method of evaluating the likelihood that a given patient's respiratory symptoms represent asthma. Making a diagnosis of asthma with confidence should lead to appropriate therapy (Crapo, Casaburi and Coates, 2000). Refuting the diagnosis can lead to a broadened differential diagnosis that includes less common disorders with similar nonspecific symptoms whose diagnosis is often greatly delayed, such as endobronchial lesions, interstitial lung disease, or pulmonary vascular disease.

Methacholine Challenge Testing: A Discussion

Increasing quantities of inhaled methacholine, a synthetic derivative of acetylcholine, induce increasing degrees of bronchospasm in susceptible individuals. Normal subjects may also experience some degree of short-lived airways narrowing if administered large amounts of methacholine, but their degree of bronchospasm typically plateaus after a modest decrease in FEV1. The clinical utility and techniques for the MCT have been recently authoritatively reviewed.1 Individuals experiencing a significant amount of airflow limitation (defined as a = 20% fall in FEV1 compared to baseline) in response to a threshold concentration of methacholine (typically < 16 mg/mL of inhaled methacholine) are considered to have airways hyperresponsiveness (AHR), ie, a positive MCT result (Crapo, Casaburi and Coates, 2000). The MCT has excellent sensitivity in identifying patients with asthma, but AHR can occur in other conditions, including viral tracheobronchitis, COPD, and congestive heart failure. Even patients with allergic rhinitis who are without chest symptoms may have a positive MCT result. Absence of AHR to methacholine challenge provides strong evidence against the diagnosis of current asthma.

The increasing significance of the MCT as a clinical and research tool is evidenced by Figure 1, which shows the number of MCT publications listed for each year from 1970 to 2000 in the National Library of Medicine PubMed directory. The search was performed using the phrase, “methacholine challenge” OR “methacholine inhalation” AND asthma. Nine citations were recovered for the entire 1970s, 168 citations for the 1980s, and 471 citations for the 1990s (Marchesani, Cecarini and Pela, 1998).

The MCT is not the only form of bronchial challenge that is clinically useful for diagnosing asthma. While inhalation of allergens and other specific inflammation-inducing agents remains the province of a few highly specialized centers, histamine inhalation has been popular in Europe. Airway challenges to respiratory heat and/or water loss reliably produce bronchospasm in asthmatics but not in normal subjects.2 Exercise testing is an unreliable method of respiratory heat and water challenge because of the difficulty in standardizing the challenge variables of minute ventilation, challenge period, and inspired air conditions of temperature and humidity (Marchesani, Cecarini and Pela, 1998). Despite low cost and simplicity, the physiologic challenge technique of eucapnic voluntary hyperventilation has not been widely ...