Methacholine challenge

In the methacholine challenge test, subjects inhale a drug that can cause the muscles in the small airways to contract. People with asthma will have a reduction in their FEVi after inhaling a low dose of this drug, reflecting increased "irritability" or bronchial h)q5erreactivity. 

Methacholine challenge Increased May show increased reactivity Normal Normal... 

Pharmacokinetics PO route onset rapid, peak 1-4 minutes, duration 15-75 minutes or 5 minutes if methacholine challenge is followed with a beta-agonist agent. Undergoes rapid hydrolysis in the plasma by acetylcholinesterase. 

Hill MR, Gotz VP, Harman E, McLeod I, Hendeles L. Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug comparison of spirometry with methacholine challenge. Chest 1986 90 698-702. 

Once baseline levels are stabilized and initial readings are taken, a methacholine challenge is given via cannulation of the tail vein using a 27-gage needle for... 

The role of thermoboxane antagonists is asthma treatment still remains uncertain. AA-2414 (41) oral administration to asthmatic subjects favorably attenuated their response to methacholine challenge [98]. Modification of a 7-oxabicyclo heptane of drug candidates by incorporation of a phenylene spacer in the a-chain afforded SQ 35,091 (42), which shows longer duration of action (tj/2 = 16 hr) [99]. GR 32191 (43) shows PGD2-induced bronchoconstriction in asthmatics at 80 mg PO [100],... 

A fall in FEVi of at least 20% following 6 minutes of near maximal exercise. Elevated eosinophil count and IgE concentration in blood. Elevated FeNO (greater than 1 2ppb). Positive methacholine challenge (PC20 FEVi less than 1 2.5 mg/mL). 

In addition to tracheobronchial secretions, bronchial smooth muscle is stimulated by the muscarinic agonists. Asthmatic patients respond with intense bronchoconstriction, secretions, and a reduction in vital capacity. These actions form the basis of the methacholine challenge test used to diagnose airway hyperreactivity. 

What is often overlooked, however, is that the process of titration destroys the meaning of other measurements. Just as it is meaningless to measure the pH of an acid once it has been neutralized by a base, it is extremely misleading to take other measurements in a clinical trial once a titration has been performed (Senn, 1989, 1993). For example, there is not much point in using pain or FEV as outcome measures in angina or asthma once exercise test titrations or methacholine challenge titrations have been carried out. 

Several studies have found an association with serum IgE level and bronchial responsiveness in both asymptomatic subjects and in patients with a history of asthma (16,29,33,41-44). In a Spanish study of 214 adults with a past history of asthma, bronchial responsiveness in response to methacholine challenge showed a linear relationship with serum IgE levels (16). This relationship was strongest for patients with active asthma compared to those without symptoms. Other studies have also found an association between high serum levels of IgE and bronchial responsiveness to methacholine or histamine challenge (41,42). In a population-based study in Italy, the odds ratio for serum IgE level > 150 kU/ L with bronchial reactivity to methacholine challenge was 3.18 after adjustment for age, sex, smoking status, asthma symptoms, and pulmonary function in this study, only IgE level and atopy were found to independently predict bronchial responsiveness (42). Two studies from the Netherlands found a similar relationship between bronchial responsiveness and serum IgE levels in patients with asthma, particularly in nonsmokers (29,43). 

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