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Annals of Allergy, Asthma & Immunology... Sep 1999The methacholine challenge test is a common investigation used to identify airway hyperresponsiveness. There has been recent debate as to whether the airway effect is... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
The methacholine challenge test is a common investigation used to identify airway hyperresponsiveness. There has been recent debate as to whether the airway effect is due to the concentration or the dose of methacholine.
OBJECTIVE
To determine whether the airway response during a methacholine challenge test is due to the concentration or the dose of methacholine.
METHODS
Ten subjects with stable, mild asthma were enrolled in this study. Two methacholine challenge tests, one with 30-second inhalations of methacholine and the other with two minute inhalations of methacholine, were performed on each subject in a random order on 2 days within a 1-week period at approximately the same time each day.
RESULTS
The geometric mean 2-minute PC20 was 1.1 mg/mL and the geometric mean 30-second PC20 was 5.7 mg/mL, 5.2-fold greater than the mean 2-minute PC20. The paired t-test comparison of the 2-minute PC20 multiplied by 4 and the 30-second PC20 revealed no significant difference (P > .2).
CONCLUSIONS
The dose of methacholine is primarily responsible for the degree of bronchial response rather than the concentration.
Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Forced Expiratory Volume; Humans; Methacholine Chloride
PubMed: 10507268
DOI: 10.1016/S1081-1206(10)62645-2 -
The Journal of Asthma : Official... Jul 2021Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the... (Meta-Analysis)
Meta-Analysis
Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis.
OBJECTIVE
Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests.
METHODS
A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies.
RESULTS
We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70-0.99), and 23.47 (95% CI, 2.51-219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28-0.73), 0.97 (95% CI, 0.94-0.99), and 35.22 (95% CI, 8.82-140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine.
CONCLUSION
Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.
Topics: Age Factors; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Humans; Mannitol; Methacholine Chloride; ROC Curve; Sensitivity and Specificity; Sex Factors
PubMed: 32138564
DOI: 10.1080/02770903.2020.1739704 -
Pulmonary Pharmacology & Therapeutics Dec 2014This study presents an animal model of native airway hyperresponsiveness (AHR). AHR is a fundamental aspect of asthma and reflects an abnormal response characterized by...
BACKGROUND
This study presents an animal model of native airway hyperresponsiveness (AHR). AHR is a fundamental aspect of asthma and reflects an abnormal response characterized by airway narrowing following exposure to a wide variety of non-immunological stimuli. Undescended testis (UDT) is one of the most common male congenital anomalies. The orl rat is a Long Evans substrain with inherited UDT. Since boys born with congenital UDT are more likely to manifest asthma symptoms, the main aim of this study was to investigate the alternative hypothesis that orl rats have greater AHR to a methacholine aerosol challenge than wild type rats.
METHODS
Long Evans wild type (n = 9) and orl (n = 13) rats were anesthetized, tracheostomized, and mechanically ventilated at 4 weeks of age. Escalating concentrations of inhaled methacholine were delivered. The methacholine potency and efficacy in the strains were measured. Respiratory resistance was the primary endpoint. After the final methacholine aerosol challenge, the short-acting β2-adrenoceptor agonist albuterol was administered as an aerosol and lung/diaphragm tissues were assayed for interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Histological and histomorphometrical analyses were performed.
RESULTS
The methacholine concentration-response curve in the orl group indicated increased sensitivity, hyperreactivity, and exaggerated maximal response in comparison with the wild type group, indicating that orl rats had abnormally greater AHR responses to methacholine. Histological findings in orl rats showed the presence of eosinophils, unlike wild type rats. β2-Adrenoceptor agonist intervention resulted in up-regulation of IL-4 diaphragmatic levels and down-regulation of IL-4 and IL-6 in the lungs of orl rats.
CONCLUSION
orl rats had greater AHR than wild type rats during methacholine challenge, with higher IL-4 levels in diaphragmatic tissue homogenates. Positive immunostaining for IL-4 was detected in lung and diaphragmatic tissue in both strains. This model offers advantages over other pre-clinical murine models for studying potential mechanistic links between cryptorchidism and asthma. This animal model may be useful for further testing of compounds/therapeutics options for treating AHR.
Topics: Administration, Inhalation; Albuterol; Animals; Anti-Asthmatic Agents; Asthma; Bronchoconstrictor Agents; Cryptorchidism; Disease Models, Animal; Dose-Response Relationship, Drug; Interleukin-4; Interleukin-6; Lung; Male; Methacholine Chloride; Rats, Long-Evans; Tumor Necrosis Factor-alpha
PubMed: 25218882
DOI: 10.1016/j.pupt.2014.09.001 -
Journal of Pharmaceutical and... Jul 2001Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to...
Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.
Topics: Bronchoconstrictor Agents; Chromatography, High Pressure Liquid; Drug Stability; Hydrogen-Ion Concentration; Kinetics; Methacholine Chloride; Osmolar Concentration; Reproducibility of Results; Sensitivity and Specificity; Solutions
PubMed: 11377069
DOI: 10.1016/s0731-7085(01)00377-6 -
Experimental Lung Research 2020This study aimed to analyze the Constant Phase Model (CPM) Coefficient of Determination (COD) and an index of harmonic distortion ([Formula: see text]) behavior in...
This study aimed to analyze the Constant Phase Model (CPM) Coefficient of Determination (COD) and an index of harmonic distortion ([Formula: see text]) behavior in intravenous methacholine dose response curve. We studied the COD and [Formula: see text] behavior of Control and Lung Inflammation (OVA) groups of mice and we proposed an alternative for moments when the CPM should not be applied. 9-week female BALB/c mice were studied, 8 of the control group (23.11 ± 1.27 g) and 11 of the lung inflammation group (OVA) (21.45 ± 2.16 g). The COD values were obtained during the respiratory mechanics assessment via Forced Oscillation Technique (FOT) and the [Formula: see text] was estimated a posteriori. Both control and OVA groups were submitted to 4 doses of Methacholine (MCh) protocol. A strong correlation between COD and [Formula: see text] was present at the last two doses (0.3 mg/kg: = -0.75, = 0.0013 and 1 mg/kg: = -0.91; < 0.0001) in the OVA group. Differences were found in doses of 0.3 mg/kg between control and OVA for the maximum values of Rn (Newtonian Resistance) and G (tissue viscous); and between groups at PBS and doses of 0.03, 0.1 and 0.3 mg/kg for H (Elastance). A similar behavior was observed for the analysis of Area Under the Curve with the exclusion of the 3 first measurements of each dose. However, in this scenario, the comparison with the maximum value presented a higher discriminatory capacity of the parameters associated with the parenchyma. During severe bronchoconstriction there is a strong negative correlation between model goodness of fit and nonlinearities levels, reinforcing that COD is a robust acceptance criterion, whether still simple and easily obtained from the ventilator. We also pointed out the area under the CPM parameters dose response curve is a useful and can be used as a complementary analysis to peak comparison following bolus injections of methacholine.
Topics: Airway Resistance; Animals; Bronchoconstriction; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Lung; Methacholine Chloride; Mice; Mice, Inbred BALB C; Ovalbumin; Pneumonia; Respiratory Function Tests; Respiratory Mechanics
PubMed: 31931646
DOI: 10.1080/01902148.2020.1711831 -
International Journal of Occupational... Mar 2020Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing...
OBJECTIVES
Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms.
MATERIAL AND METHODS
Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed.
RESULTS
Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol.
CONCLUSIONS
The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.
Topics: Adult; Allergens; Asthma, Occupational; Bronchial Provocation Tests; Female; Humans; Male; Mannitol; Methacholine Chloride; Middle Aged; Single-Blind Method
PubMed: 32080681
DOI: 10.13075/ijomeh.1896.01459 -
Journal of Physiology and Pharmacology... Jun 2014Cardiovascular disease is the most frequent cause of death in people with chronic respiratory disease. The cause of this association has been attributed to airway... (Randomized Controlled Trial)
Randomized Controlled Trial
Cardiovascular disease is the most frequent cause of death in people with chronic respiratory disease. The cause of this association has been attributed to airway obstruction leading to cardiovascular dysfunction (increased central blood pressure (BP) and aortic stiffness). However, this has never been experimentally tested. Methacholine is routinely used to stimulate airway function changes that mimic airway pathology. This study aimed to determine the cardiovascular effects of methacholine-induced airway obstruction. Fifteen healthy young adults (aged 22.9±2.5 years; 4 male; mean±S.D.) underwent a bronchial challenge test (randomized, blinded, cross-over design) in which they received nebulized methacholine inhalation in serially increasing concentrations (from 0.39 to 25 mg/ml) or saline (0.9%; control) on two separate days. Bronchoconstriction was assessed by forced expiratory volume at one second (FEV1) and cardiovascular effects by augmentation index, brachial BP, central BP, heart rate and aortic stiffness. Methacholine significantly decreased FEV1 from baseline to peak inhaled concentration compared with saline (-0.48±0.34 vs. -0.07±0.16 L; p<0.001), but there was no between-group change in augmentation index (1.6±7.0 vs. 3.7±10.2% p=0.49), brachial systolic BP (-3.3±7.6 vs. -4.7±5.7 mmHg; p=0.59), central systolic BP (-1.1±5.2 vs. -0.3±5.5 mmHg; p=0.73), heart rate (0.4±7.1 vs. -0.8±6.6 bpm; p=0.45) or aortic stiffness (0.2±1.3 vs. 0.8±1.8 m/s; p=0.20; n=12). Thus, methacholine induced airway obstruction does not acutely change brachial BP or central haemodynamics. This finding refutes the notion that airway obstruction per se leads to cardiovascular dysfunction, at least in healthy individuals in the acute setting.
Topics: Administration, Inhalation; Adolescent; Adult; Airway Obstruction; Bronchial Provocation Tests; Bronchoconstriction; Cardiovascular System; Cross-Over Studies; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Young Adult
PubMed: 24930512
DOI: No ID Found -
Annals of Allergy, Asthma & Immunology... May 2010
Topics: Administration, Inhalation; Adult; Asthma; Bronchial Provocation Tests; Female; Histamine; Humans; Male; Methacholine Chloride; Sensitivity and Specificity
PubMed: 20491150
DOI: 10.1016/j.anai.2010.03.002 -
Canadian Journal of Anaesthesia =... Nov 2011
Topics: Anesthetics, Inhalation; Animals; Bronchial Hyperreactivity; Bronchoconstriction; Desflurane; Isoflurane; Methacholine Chloride; Methyl Ethers; Muscarinic Agonists; Sevoflurane
PubMed: 21866429
DOI: 10.1007/s12630-011-9577-4 -
The New England Journal of Medicine May 2011
Topics: Asthma; Bronchi; Bronchoconstriction; Eosinophils; Humans; Methacholine Chloride
PubMed: 21612476
DOI: 10.1056/NEJMe1103121