Retrospective Analyses of Methacholine Inhalation Challenges

doi:10.1378/chest.105.4.1082

Chest

Volume 105, Issue 4, April 1994, Pages 1082-1088

https://doi.org/10.1378/chest.105.4.1082 Get rights and content

We retrospectively analyzed 198 methacholine inhalation challenges (MICs) of symptomatic patients with normal results of lung examinations, spirometry, and chest radiographs. During MIC, five parameters (FEV₁, FEF25-75%, FVC, sCaw, TGV) were measured. Using established changes in these parameters at ≤8 mg/ml methacholine, there were 175 positive tests (no false positives) and 23 negative tests (15 true negatives, 5 false negatives, and 3 unavailable for follow-up). The MIC sensitivity determined by FEV₁ responses was significantly lower than the sensitivity using responses in either three (FEV₁, FEF25-75%, and FVC; p<0.001) or five (FEV₁, FEF25-75%, FVC, sGaw, and TGV; p<0.001) parameter sets. Sensitivities were 60.6 percent, 91.1 percent, and 97.2 percent, respectively. All positive MICs (100 percent) were identified by examining changes in the five-parameter set vs 97.3 percent in the three-parameter set; it was a significant difference at p<0.01. We conclude that the measurement and analysis of non-FEV₁ parameters in addition to FEV₁ significantly increases the sensitivity of the MIC.

Section snippets

Subjects

There were 63 male and 136 nonpregnant female patients aged 7 to 75 years with a mean age of 34 years who presented to a subspecialty practice of allergy and immunology as selfreferrals or referrals from primary care physicians. Symptom duration ranged from 3 to 36 months (mean, 5 months) prior to MIC. Those patients who were smokers (n=40) did not smoke at least 12 h prior to MIC. Exposure to allergens was not controlled. There were no patients with recent influenza or rubella immunizations.

RESULTS

One hundred ninety-nine baseline PFTs and MICs were performed in a symptomatic patient sample. One challenge was discontinued after the patient experienced coughing and nasal congestion at the 0.25-mg/ml concentration of methacholine and refused further testing. No changes in airflow were noted. The remaining 198 patients experienced no severe immediate or delayed reactions that could not be managed by β-agonist therapy. Results were analyzed and patients were divided into two groups based on

DISCUSSION

The American Thoracic Society criteria for the diagnosis of clinical asthma includes airway hyperreactivity, airway obstruction, and therapeutic responsiveness to bronchodilators or glucocorticoids.²² A complete history, physical examination, and evidence of reversible airways obstruction are usually sufficient to diagnose asthma. However, some patients present with ill-defined lower respiratory tract symptoms or complain of tightness, cough, or dyspnea with normal baseline spirometry values.10

REFERENCES (43)

S Weiss et al.
The velocity of blood flow in health and disease as measured by the effect of histamine in the minute vessels?
Am Heart J
(1929)
JJ Curry et al.
Measurement of vital capacity in asthmatic subjects receiving histamine and acetyl-beta-methacholine—a clinical study?
J Allergy
(1948)
H Chai et al.
Standardization of bronchial inhalation challenge procedures?
J Allergy Clin Immunol
(1975)
FE Hargreave et al.
Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance?
J Allergy Clin Immunol
(1981)
SS Braman et al.
Bronchoprovocation testing?
Clin Chest Med
(1989)
RG Townley et al.
Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects?
J Allergy Clin Immunol
(1975)
RG Townley et al.
Methacholine inhalation challenge studies?
J Allergy Clin Immunol
(1979)
RW Light et al.
The one best test for evaluating effects of bronchodilator therapy?
Chest
(1977)
HR Smith et al.
The utility of spirometry in the diagnosis of reversible airways obstruction?
Chest
(1992)
F Haas et al.
Use of maximum expiratory flow-volume curve parameters in the assessment of exercise-induced bronchospasm?
Chest
(1993)

JE Fish et al.

Measurements of responsiveness in bronchoprovocation testing?

J Allergy Clin Immunol

(1979)

DW Cockcroft et al.

Sensitivity and specificity of histamine PC20 determination in a random selection of young college students?

J Allergy Clin Immunol

(1992)

HH Dale et al.

The physiological action of beta-iminazolylethylamine?

J Physiol

(1910)

HL Alexander et al.

Bronchial asthma: response to pilocarpine and epinephrine?

Arch Intern Med

(1921)

S Weiss et al.

The systemic effects of histamine in man with special reference to the responses of the cardiovascular system?

Arch Intern Med

(1932)

JJ Curry

The action of histamine on the respiratory tract in normal and asthmatic subjects?

J Clin Invest

(1946)

JJ Curry

Comparative action of acetyl-beta-methacholine and histamine on the respiratory tract in normal, patients with hay fever and subjects with bronchial asthma?

J Clin Invest

(1947)

R Tiffeneau et al.

Epreuve de bronchoconstriction et de bronchodilation par aerosols?

Bull Acad Med

(1945)

R Tiffeneau

Evaluation of degree of asthma by pharmacodynamic test: measure of acetylcholine excitability of lung?

Ann Med

(1955)

RR Rosenthal

Introduction: methacholine challenge: research becomes practice?

Allergy Proc

(1989)

RR Rosenthal

Inhalation challenge in asthma

Cited by (26)

Bronchoprovocation Testing in Asthma: An Update
2018, Immunology and Allergy Clinics of North America
Citation Excerpt :
The reported sensitivity and specificity of the methacholine challenge test (MCT) has varied depending on the study population tested. In studies with large sample sizes, sensitivity ranged from 51%117 to 100%118 and specificity ranged from 49%119 to 100% (Table 2).117–131 Much of these data are based on older clinical trials.
Comparison of changes in lung function measured by plethymography and IOS after bronchoprovocation
2013, Respiratory Medicine
Citation Excerpt :
Plethysmograph and spirometry assessments during bronchial inhalation challenges show that up to 20% of subjects demonstrate a positive response in sRaw without sufficient response in FEV1.34 Likewise, the provocative concentration of histamine causing a 40% fall in sGaw was more sensitive than PC20 FEV1 in detecting bronchoconstriction,35 and adding measurement of sGaw to FEV1 was shown to increase the sensitivity of methacholine challenges.36 Therefore it is not surprising to observe that sRaw and its reciprocal value, aGaw, are more sensitive than FEV1 to allergen- and methacholine-induced bronchoconstriction.
Lung function tests are essential for the diagnosis and management of bronchial asthma. Impulse oscillation (IOS) system is an alternative way to measure lung mechanics for some patients. We investigated the relative sensitivities of IOS, body plethysmography and spirometry in detecting allergen- and methacholine-induced bronchoconstriction.
Twenty-two subjects had single allergen inhalation and 8 subjects had 3 methacholine challenges. The tests were stopped when FEV₁ fell by 20%. Lung function was measured using IOS (R5, R20, R5-R20, X5, AX, fres), plethysmography (sRaw, sGaw, FRC, lung volumes) and spirometry (FEV₁, FVC, PEF, FEF_50%) during inhalation challenges, and expressed as percent change from pre-challenge baseline.
All subjects were non-smoking adults with mild allergic asthma. Following allergen challenges, the most sensitive IOS index was R5–R20 and the most sensitive plethysmography and spirometry measurements were sRaw, sGaw and FEF_50%. Following methacholine challenge the most sensitive IOS index was AX, the most sensitive plethysmography measurement was sRaw. Overall, IOS (R5–R20, AX, X5 Hz) proved to be more sensitive than plethysmography and spirometry measurements following allergen-induced and methacholine-induced bronchoconstriction.
Our result shows that IOS is more sensitive than other lung function tests following allergen and methacholine challenge. In addition, IOS can act as an alternative measurement technique of airway resistance and obstruction in patients where manoeuvres involved in plethysmography and spirometry prove difficult to perform.
Bronchoprovocation Testing in Asthma
2012, Immunology and Allergy Clinics of North America
Methacholine challenge test: Diagnostic characteristics in asthmatic patients receiving controller medications
2012, Journal of Allergy and Clinical Immunology
Citation Excerpt :
The sensitivity and specificity of the MCT observed in previous studies have varied depending on the study population tested.5-10,12-14,21 In studies with large sample sizes, sensitivity ranged from 51%12 to 100%,6 and specificity ranged from 49%14 to 100% (Table IV)5-10,12-14,21 However, the current ATS guidelines suggest that MCTs can be used to clinically exclude asthma if the PC20 is greater than 16 mg/mL in the proper clinical setting.15 This conclusion was based mainly on studies before ICS use had become a mainstay treatment for asthma.
The methacholine challenge test (MCT) is commonly used to assess airway hyperresponsiveness, but the diagnostic characteristics have not been well studied in asthmatic patients receiving controller medications after the use of high-potency inhaled corticosteroids became common.
We investigated the ability of the MCT to differentiate participants with a physician's diagnosis of asthma from nonasthmatic participants.
We conducted a cohort-control study in asthmatic participants (n = 126) who were receiving regular controller medications and nonasthmatic control participants (n = 93) to evaluate the sensitivity and specificity of the MCT.
The overall sensitivity was 77% and the specificity was 96% with a threshold PC₂₀ (the provocative concentration of methacholine that results in a 20% drop in FEV₁) of 8 mg/mL. The sensitivity was significantly lower in white than in African American participants (69% vs 95%, P = .015) and higher in atopic compared with nonatopic (82% vs 52%, P = .005). Increasing the PC₂₀ threshold from 8 to 16 mg/mL did not noticeably improve the performance characteristics of the test. African American race, presence of atopy, and lower percent predicted FEV₁ were associated with a positive test result.
The utility of the MCT to rule out a diagnosis of asthma depends on racial and atopic characteristics. Clinicians should take into account the reduced sensitivity of the MCT in white and nonatopic asthmatic patients when using this test for the diagnosis of asthma.
Methacholine challenge testing: Identifying its diagnostic role, testing, coding, and reimbursement
2007, Chest
Citation Excerpt :
The varied clinical presentations of asthma including, wheezing,17 high blood total eosinophil count,18 and cough19 are not specific for the diagnosis of asthma. MCT is often considered in the clinical setting of asthma-like symptoms with normal or near-normal spirometry findings or when the postbronchodilation FEV1 improves but is not greater than 12% and 200 mL.20 While the most common clinical indication for MCT is in patients with a history of asthma-like symptoms but normal spirometry findings, either exhaled nitric oxide or the MCT results can also be used to titrate the daily dose of inhaled corticosteroids or prednisone in patients who are known to have asthma.21
Methacholine challenge testing (MCT), also sometimes described as bronchoprovocation testing, is widely performed for both research and diagnostic purposes. MCT is clinically useful when the patient presents with a history of symptoms suggesting asthma, but spirometry findings are normal. Typically, MCT is performed in a pulmonary function laboratory, a clinic, or a physician's office. MCT requires time, effort, and understanding. Two standard testing regimes are identified along with proper coding and reimbursement methodologies.
Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV<inf>1</inf> responses, and methacholine inhalation challenges in the evaluation of suspected asthma
2001, Chest
Citation Excerpt :
An MIC was scheduled 3 to 4 weeks after the initial visit. The study protocol for MIC closely followed recommendations made by the Canadian Thoracic Society,34 Rijcken et al,35 and as previously reported by our group.36 A spirometry system (model 2200; Sensormedics; Yorba Linda, CA) and a variable-pressure, constant-volume body plethysmograph (model 6200; Sensormedics) were used.
The validity of peak expiratory flow variation (PEFvar) as defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines as a diagnostic tool for suspected asthma or its comparative value to methacholine inhalation challenge (MIC) or postbronchodilator (BD) FEV₁ responses has not been formally assessed. We prospectively analyzed the correlation of 28 different PEFvar indexes (including 4 NHLBI-compatible indexes) with MIC and pre-BD and post-BD FEV₁ responses in suspected asthmatic subjects with normal findings on lung examination, chest radiography, and baseline spirometry.
Participants were asked to record peak expiratory flow four times daily for 2 to 3 weeks, followed by an MIC. During a minimum 6-month follow-up period, a clinical diagnosis of asthma was made or ruled out based on testing results and response to antiasthma therapy.
Medical school-affiliated subspecialty private practice of allergy, asthma, and immunology.
One hundred twenty-one suspected asthmatic patients with normal findings on lung examination, chest radiography, and baseline spirometry.
Fifty-seven subjects completed both the peak flow diary and the MIC and were accepted for statistical analysis. There were no statistically significant correlations between any peak expiratory flow index and MIC. Among the three diagnostic tools evaluated, MIC had the highest sensitivity (85.71%). All the PEFvar indexes and post-BD responses had low sensitivity and high false-negative rates.
PEFvar and post-BD FEV₁ responses are poor substitutes for MIC in the assessment of patients with suspected asthma with normal findings on lung examination, chest radiography, and spirometry. Our findings warrant a reconsideration of the NHLBI guidelines recommendation of the utility of PEFvar as a diagnostic tool for asthma in clinical practice.

View all citing articles on Scopus

: Manuscript received December 10, 1992; revision accepted September 20, 1993.

View full text

Chest

Retrospective Analyses of Methacholine Inhalation Challenges

Section snippets

Subjects

RESULTS

DISCUSSION

Am Heart J

J Allergy

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Chest Med

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

Chest

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

The physiological action of beta-iminazolylethylamine?

J Physiol

Bronchial asthma: response to pilocarpine and epinephrine?

Arch Intern Med

The systemic effects of histamine in man with special reference to the responses of the cardiovascular system?

Arch Intern Med

The action of histamine on the respiratory tract in normal and asthmatic subjects?

J Clin Invest

Comparative action of acetyl-beta-methacholine and histamine on the respiratory tract in normal, patients with hay fever and subjects with bronchial asthma?

J Clin Invest

Epreuve de bronchoconstriction et de bronchodilation par aerosols?

Bull Acad Med

Evaluation of degree of asthma by pharmacodynamic test: measure of acetylcholine excitability of lung?

Ann Med

Introduction: methacholine challenge: research becomes practice?

Allergy Proc

Inhalation challenge in asthma