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Annals of Allergy, Asthma & Immunology... Apr 2017
Clinical Trial
Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride
PubMed: 28274734
DOI: 10.1016/j.anai.2017.01.010 -
Respiratory Physiology & Neurobiology Oct 2022BALB/c mice from both sexes underwent one of two nebulized methacholine challenges that were preceded by a period of 20 min either with or without tone induced by...
BALB/c mice from both sexes underwent one of two nebulized methacholine challenges that were preceded by a period of 20 min either with or without tone induced by repeated contractions of the airway smooth muscle. Impedance was monitored throughout and the constant phase model was used to dissociate the impact of tone on conducting airways (R - Newtonian resistance) versus the lung periphery (G and H - tissue resistance and elastance). The effect of tone on smooth muscle contractility was also tested on excised tracheas. While tone markedly potentiated the methacholine-induced gains in H and G in both sexes, the gain in R was only potentiated in males. The contractility of female and male tracheas was also potentiated by tone. Inversely, the methacholine-induced gain in hysteresivity (G/H) was mitigated by tone in both sexes. Therefore, the tone-induced muscle hypercontractility impacts predominantly the lung periphery in vivo, but also promotes further airway narrowing in males while protecting against narrowing heterogeneity in both sexes.
Topics: Animals; Female; Lung; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth; Trachea
PubMed: 35716869
DOI: 10.1016/j.resp.2022.103938 -
Annals of Allergy, Asthma & Immunology... Jun 2020
Topics: Albuterol; Asthma; Bronchoconstrictor Agents; Disease Management; Female; Humans; Male; Methacholine Chloride; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 32244033
DOI: 10.1016/j.anai.2020.03.025 -
Validation of the clinical utility of sGaw as a response variable in methacholine challenge testing.Respirology (Carlton, Vic.) May 2023Airway hyperresponsiveness (AHR) is commonly assessed by a methacholine challenge test (MCT), during which a provocative concentration causing a 20% reduction in forced...
BACKGROUND AND OBJECTIVE
Airway hyperresponsiveness (AHR) is commonly assessed by a methacholine challenge test (MCT), during which a provocative concentration causing a 20% reduction in forced expiratory volume in 1 second (FEV ) (PC ) < 8 mg/ml is considered a positive response. However, a fall in specific airway conductance (sGaw) may also have clinical significance. The purpose of this study was to assess whether AHR determined by a provocative concentration causing a 40% reduction in sGaw (PC ) < 8 mg/ml corresponds to a clinical diagnosis of asthma.
METHODS
We analysed the changes in spirometry, lung volumes and sGaw during MCT in 211 randomly selected patients being evaluated for AHR to support a clinical diagnosis of asthma.
RESULTS
The mean (SD) age of the group was 53 (15) years, with 141 women (67%). Overall lung function was normal, with FEV = 92 (15) % predicted, total lung capacity = 97 (13) % predicted and sGaw = 0.19 (0.15-0.23) L/s/cm H O/L, (median, 25-75 IQR). There were many more patients who responded by PC only (n = 120) than who responded by PC (n = 52). There was no significant difference in asthma diagnosis between the PC (98%) and PC (93%) groups, and we estimate 34% of patients with a diagnosis of asthma would have been classified as having no AHR if only the FEV criterion was used.
CONCLUSION
Changes in sGaw during MCT indicate clinically significant AHR in support of a clinical diagnosis of asthma among patients being evaluated for asthma.
Topics: Humans; Female; Middle Aged; Methacholine Chloride; Bronchoconstrictor Agents; Asthma; Bronchial Provocation Tests; Respiratory Hypersensitivity; Forced Expiratory Volume
PubMed: 36478621
DOI: 10.1111/resp.14431 -
Clinical and Experimental Allergy :... Apr 1998
Review
Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Humans; Methacholine Chloride
PubMed: 9641585
DOI: 10.1046/j.1365-2222.1998.0280s1015.x -
Chest May 2002Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and...
OBJECTIVE
Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and Drug Administration-required labeling. The purpose of this report was to determine whether freezing methacholine solutions in unit-dose syringes would allow less frequent preparation.
DESIGN
Diluent containing 0.5% sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare 11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three milliliters of each dilution was placed into 5-mL polypropylene syringes and immediately frozen. Methacholine concentrations were determined using a validated high-performance liquid chromatography assay after preparation (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were allowed to thaw to room temperature. An additional set of each dilution was stored at room temperature for 24 h after thawing and then analyzed for methacholine.
RESULTS
Samples > or = 0.062 mg/mL analyzed immediately after thawing retained > or = 90% of labeled potency for at least 6 months, while the 0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h after thawing lost potency.
CONCLUSION
If prepared and stored in unit-dose syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be prepared at 4-month intervals. Once thawed, unused methacholine solutions should be discarded.
Topics: Bronchial Provocation Tests; Bronchoconstrictor Agents; Chromatography, High Pressure Liquid; Drug Packaging; Drug Stability; Drug Storage; Freezing; Humans; Methacholine Chloride; Syringes
PubMed: 12006455
DOI: 10.1378/chest.121.5.1634 -
Annals of Allergy, Asthma & Immunology... Jun 2007
Topics: Administration, Inhalation; Bronchial Provocation Tests; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Humans; Methacholine Chloride; Nebulizers and Vaporizers; Tidal Volume
PubMed: 17601278
DOI: 10.1016/S1081-1206(10)60744-2 -
Chest Dec 1990One hundred consecutive outpatients with symptoms suggestive of asthma who came to the Pulmonary Function Laboratory for a methacholine challenge test were studied. In...
One hundred consecutive outpatients with symptoms suggestive of asthma who came to the Pulmonary Function Laboratory for a methacholine challenge test were studied. In addition to the forced expiratory maneuvers, forced inspiratory maneuvers were performed before and after the maximal response to methacholine. In 24 patients, the methacholine challenge suggested that they had asthma (forced expiratory volume in 1 s [FEV1] decrease greater than or equal to 20 percent). Six of these 24 patients also had a decrease in maximal forced inspiratory flow (FIFmax) greater than or equal to 20 percent and nine had a decrease in forced inspiratory flow at 50 percent of vital capacity (FIF50) greater than or equal to 20 percent, suggesting that bronchoconstriction can cause decreased inspiratory as well as expiratory flows. In 76 patients, the methacholine challenges were "negative" (FEV1 decrease less than or equal to 20 percent), suggesting that they did not have asthma. Nevertheless, in 11 of these 76 patients the FIFmax decrease was greater than or equal to 20 percent, and in 14 patients the FIF50 decrease was greater than or equal to 20 percent, suggesting that intermittent central airway obstruction is responsible for these patients' symptoms.
Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Child; Child, Preschool; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Pulmonary Ventilation
PubMed: 2245684
DOI: 10.1378/chest.98.6.1426 -
International Journal of Pharmaceutics Mar 2008The methacholine (MCH) challenge test is performed to detect bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted by inhaling spasmogen... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The methacholine (MCH) challenge test is performed to detect bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted by inhaling spasmogen substances at increasing doses and measuring FEV1-PD20 variation following the bronchoconstriction evoked.
AIM
This paper describes a new method for MCH challenge test using pre-metered respirable powders of MCH at different doses for facilitating test execution. The availability of a series of pre-metered doses gives higher control over aerosolized dose and fine particle fraction (respirable dose), improving the accuracy and repeatability of the test. Dosimetric tests with MCH solution and pre-dosed powder challenge tests were clinically compared.
METHODS AND MATERIALS
The inhalation powders were prepared by spray drying of solutions of methacholine, mannitol and hydroxypropylmethylcellulose in which different concentrations of MCH were included. The methacholine powders prepared were carefully characterized in terms of aerodynamic properties.
RESULTS
Inhalation powders containing methacholine from 12.5 to 200 microg per metered dose, having a fine particle fraction between 40 and 60%, were prepared using mannitol and cellulose polymer. Eighteen subjects (12 hyperresponsive and six normal) were subjected to both the MCH solution and powder tests in random sequence. No significant differences in FEV1 and PD20 values were found between the challenge tests performed with liquid and powder formulations of methacholine.
CONCLUSIONS
Powders of MCH having high respirability of the delivered doses can be prepared by spray drying. They allow for the performance of a challenge test using a dry powder inhaler. The powder dose series can be an alternative to the current dosimetric test with MCH solutions.
Topics: Administration, Inhalation; Adult; Aerosols; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Equipment Design; Female; Forced Expiratory Volume; Humans; Hypromellose Derivatives; Male; Mannitol; Metered Dose Inhalers; Methacholine Chloride; Methylcellulose; Particle Size; Powders; Predictive Value of Tests; Reproducibility of Results; Technology, Pharmaceutical
PubMed: 18055141
DOI: 10.1016/j.ijpharm.2007.10.025 -
The Journal of Allergy and Clinical... Feb 2013Both leukotriene D(4) (LTD(4)) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Both leukotriene D(4) (LTD(4)) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain unexplored.
OBJECTIVES
We sought to compare the 2 tests and classify leukotriene-responsiveness subtypes in asthmatic patients.
METHODS
In this randomized cross-over study we enrolled healthy subjects and asthmatic patients with different control statuses. All subjects underwent both tests with a 2- to 14-day interval. Distribution and correlation of cumulative doses inducing a 20% decrease in FEV(1), LTD(4)/methacholine potency ratio, diagnostic value, and adverse events were recorded and analyzed. Asthmatic patients with a lower cumulative dose for LTD(4) and a higher leukotriene/methacholine potency ratio than geometric means were regarded as leukotriene responsive.
RESULTS
Twenty patients with uncontrolled, 22 with partly controlled, and 20 with controlled asthma and 21 healthy subjects were enrolled. Geometric means of cumulative doses for LTD(4) and methacholine (0.272 nmol vs 0.945 μmol) were lowest in patients with uncontrolled asthma, followed by those with partly controlled (0.387 nmol vs 1.933 μmol) and controlled (1.484 nmol vs 3.946 μmol) asthma. The average potency ratio was highest in those with partly controlled asthma (5000.2), followed by those with uncontrolled (3477.7) and controlled (2702.6) asthma. Eighteen leukotriene-responsive asthmatic patients (29.03%) with a cumulative dose of LTD(4) of 0.533 nmol or less and a potency ratio of 3647 or greater were identified. Adverse events, including tachypnea and chest tightness, were similar and mild. No serious adverse event was reported.
CONCLUSION
Diagnostic value and safety were ideal in both tests. The combination of cumulative dose for LTD(4) and potency ratio might be useful to identify leukotriene-responsive asthmatic patients.
Topics: Administration, Inhalation; Adult; Asthma; Bronchi; Bronchial Provocation Tests; Case-Control Studies; Cross-Over Studies; Humans; Leukotriene D4; Methacholine Chloride
PubMed: 23040886
DOI: 10.1016/j.jaci.2012.08.020