Methacholine inhalation challenge: a shorter, cheaper and safe approach

Abstract

Methacholine inhalation challenge: a shorter, cheaper and safe approach. G. Izbicki, E. Bar-Yishay. #ERS Journals Ltd 2001. ABSTRACT: Increased nonspeci®c bronchial hyperresponsiveness to pharmacological agents such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement of airway reactivity is quite sensitive but testing is tedious, and time and money consuming. The present aim was, therefore, to design the shortest possible, yet safe inhalation challenge protocol applicable for a lung function referral centre.All records of studies performed in our institution during 1996 were analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume in one second/ forced vital capacity (FEV1/FVC) ¢0.7 (n=449). It was questioned what the initial dose should be, and whether some inhalation steps could have been skipped without losing pertinent information and/or causing an adverse response (a fall in FEV1 >40%). When unavailable, provocative dose causing a 20% fall in FEV1 (PD20) values were obtained by linear inter-or extrapolation of the existing data.The present study showed that three-fold concentration steps could have been employed with minimal change in outcome. Only 15/449 patients (3.3%) would have experienced a severe response. Five subjects (of 169, 3.0%) with FEV1/FVCbl 0.7±0.8 reacted to inhalation up to 0.073 mmol. Four subjects (of 280, 1.4%) with FEV1/ FVCbl¢0.8 reacted to inhalation up to 0.219 mmol.The authors suggest that: 1) an initial dose of 0.219 mmol (initial concentration= 0.21 mg . mL -1 ) may be used when the baseline ratio of forced expiratory volume in one second to forced vital capacity ¢0.8 and 0.073 mmol (initial concentration=0.07 mg . mL -1 ) when the baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper and 30.2% faster, yet just as safe; and 3) other abbreviated protocols used in epidemiologic settings may not be applicable in a referral centre setting.

Truncating the Dose Range for Methacholine Challenge Tests: Three Occupational Studies

“…Two more recent studies evaluated the effectiveness and safety of shorter methacholine challenge protocols. 17,19 Izbicki and BarYishal 17 performed a MCT in a lung function referral center and the initial methacholine concentration was 0.03 mg/mL followed by tripling concentrations up to 8 mg/mL. The authors concluded that an initial concentration of 0.21 mg/mL may be used when the baseline ratio of FEV 1 / FVC is greater or equal to 0.80, and a tripling dose protocol is easier to perform and safe.…”

“…Although abbreviated methacholine protocols are attractive and several alternatives have been examined, the impact of excluding higher concentrations has not been previously evaluated. Several investigators have evaluated the impact of deleting low concentrations, however their focus was on the safety of the test, [15][16][17][18][19] rather than on the measures of responsiveness. Chatham et al 15 compared a full protocol methacholine challenge test, with an abbreviated test in 23 subjects, of which 13 were asthmatics.…”

“…The impact of shorter versus longer protocols on the outcomes of the challenge test has already been investigated in several studies. [15][16][17][18][19] By comparing protocols that differ in dosing procedure and concentrations of either methacholine or histamine, these studies have shown that shorter protocols can be as effective as longer protocols in capturing hyper-responsive subjects. However, there is still uncertainty about the effect of truncating dose protocols on bronchial responsiveness among borderline responsive subjects.…”

Effect of Inspiratory Flow on Methacholine Challenge in Children

“…The median age of children (15 boys, 10 girls) who completed the protocol was 12.2 years (range [8][9][10][11][12][13][14][15][16]. The median age of children (15 boys, 10 girls) who completed the protocol was 12.2 years (range [8][9][10][11][12][13][14][15][16].…”

Evaluation of an Abbreviated Adenosine Monophosphate Bronchial Challenge

“…This procedure has been shown to take from 35 to 65 min. 2,3 There have been numerous efforts to reduce the length of bronchial challenge tests: (1) shortening the length of time between doses, 4 (2) employing threefold or fourfold jumps rather than doubling steps, [3][4][5] or (3) starting the challenge at a higher concentration. 6,7 A direct challenge using histamine at 1-min intervals relies on a cumulative dose to provoke bronchoconstriction 4 ; however, histamine administered at 5-min intervals has been shown to be entirely independent of cumulative dose.…”