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The Senior Care Pharmacist Jan 2023To investigate potential reasons for unusually high incidence of negative Methacholine Challenge Tests (MCT), following standardized MCT medication-hold protocol, in...
To investigate potential reasons for unusually high incidence of negative Methacholine Challenge Tests (MCT), following standardized MCT medication-hold protocol, in older people with physician-diagnosed asthma. An analysis of a longitudinal observational parent study of asthma. Community-dwelling participants were evaluated in an outpatient clinic and at home. Screening inclusion criteria for the parent study included 60 years of age or older, physician diagnosis of asthma, and a positive response to at least one of six asthma screening questions. Participants were enrolled in the study if they also demonstrate either: (1) a postbronchodilator administration response showing an increase of at least 12% and 200 mL in forced expiratory volume or an increase of at least 12% and 200 mL in forced vital capacity, or (2) an MCT result of PC20 ≤ 16 mg/mL (indicating bronchial hyper-responsiveness, MCT positive). Exclusion criteria included diagnosis of cognitive impairment or dementia, residing in a long-term care facility, more than 20 pack/ year smoking history or a history of smoking within the previous five years, inability to perform pulmonary function testing maneuvers, and a Prognostic Index score of greater than 10. Analysis of participant data for non-medication- and medication-exposure factors for association with negative MCT results. Anticholinergic burden and statin use were positively associated with negative MCT. Medications not accounted for in medication-hold protocols, and concurrently in use, may impact clinical tests and outcomes.
Topics: Humans; Aged; Methacholine Chloride; Polypharmacy; Asthma; Bronchial Provocation Tests; Forced Expiratory Volume
PubMed: 36751917
DOI: 10.4140/TCP.n.2023.29 -
Respiratory Medicine Nov 2017
Topics: Administration, Inhalation; Adult; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Diagnosis, Differential; Dose-Response Relationship, Drug; Female; Humans; Male; Methacholine Chloride; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Symptom Assessment
PubMed: 29229081
DOI: 10.1016/j.rmed.2017.10.002 -
Revue Des Maladies Respiratoires Sep 2018
Topics: Asthma; Bronchial Provocation Tests; Diagnosis, Differential; Fibrin Fibrinogen Degradation Products; Humans; Methacholine Chloride; Pulmonary Embolism; Respiratory Function Tests
PubMed: 30189993
DOI: 10.1016/j.rmr.2018.08.008 -
Experimental Lung Research 2023Force adaptation is a process whereby the contractile capacity of the airway smooth muscle increases during a sustained contraction (aka tone). Tone also increases the...
Force adaptation is a process whereby the contractile capacity of the airway smooth muscle increases during a sustained contraction (aka tone). Tone also increases the response to a nebulized challenge with methacholine , presumably through force adaptation. Yet, due to its patchy pattern of deposition, nebulized methacholine often spurs small airway narrowing heterogeneity and closure, two important enhancers of the methacholine response. This raises the possibility that the potentiating effect of tone on the methacholine response is not due to force adaptation but by furthering heterogeneity and closure. Herein, methacholine was delivered homogenously through the intravenous (i.v.) route. Female and male BALB/c mice were subjected to one of two i.v. methacholine challenges, each of the same cumulative dose but starting by a 20-min period either with or without tone induced by serial i.v. boluses. Changes in respiratory mechanics were monitored throughout by oscillometry, and the response after the final dose was compared between the two challenges to assess the effect of tone. For the elastance of the respiratory system (E), tone potentiated the methacholine response by 64 and 405% in females (37.4 ± 10.7 61.5 ± 15.1 cmHO/mL; = 0.01) and males (33.0 ± 14.3 166.7 ± 60.6 cmHO/mL; = 0.0004), respectively. For the resistance of the respiratory system (R), tone potentiated the methacholine response by 129 and 225% in females (9.7 ± 3.5 22.2 ± 4.3 cmHO·s/mL; = 0.0003) and males (10.7 ± 3.1 34.7 ± 7.9 cmHO·s/mL; < 0.0001), respectively. As previously reported with nebulized challenges, tone increases the response to i.v. methacholine in both sexes; albeit sexual dimorphisms were obvious regarding the relative resistive elastic nature of this potentiation. This represents further support that tone increases the lung response to methacholine through force adaptation.
Topics: Male; Female; Animals; Mice; Methacholine Chloride; Lung; Respiratory Mechanics; Bronchial Provocation Tests; Airway Resistance
PubMed: 37477352
DOI: 10.1080/01902148.2023.2237127 -
Role of hyperpnea in the relaxant effect of inspired CO on methacholine-induced bronchoconstriction.Journal of Applied Physiology... May 2022Inhaling carbon dioxide (CO) in humans is known to cause inconsistent effects on airway function. These could be due to direct effects of CO on airway smooth muscle or...
Inhaling carbon dioxide (CO) in humans is known to cause inconsistent effects on airway function. These could be due to direct effects of CO on airway smooth muscle or to changes in minute ventilation (V̇e). To address this issue, we examined the responses of the respiratory system to inhaled methacholine in healthy subjects and subjects with mild asthma while breathing air or gas mixtures containing 2% or 4% CO. Respiratory mechanics were measured by a forced oscillation technique at 5 Hz during tidal breathing. At baseline, respiratory resistance (R) was significantly higher in subjects with asthma (2.53 ± 0.38 cmHO·L·s) than healthy subjects (2.11 ± 0.42 cmHO·L·s) ( = 0.008) with room air. Similar values were observed with CO 2% or 4% in the two groups. V̇e, tidal volume (V), and breathing frequency (BF) significantly increased with CO-containing mixtures ( < 0.001) with insignificant differences between groups. After methacholine, the increase in R and the decrease in respiratory reactance (X) were significantly attenuated up to about 50% with CO-containing mixtures instead of room air in both asthmatic ( < 0.001) and controls ( < 0.001). Mediation analysis showed that the attenuation of methacholine-induced changes in respiratory mechanics by CO was due to the increase in V̇e ( = 0.006 for R and = 0.014 for X) independently of the increase in V or BF, rather than a direct effect of CO. These findings suggest that the increased stretching of airway smooth muscle by the CO-induced increase in V̇e is a mechanism through which hypercapnia can attenuate bronchoconstrictor responses in healthy subjects and subjects with mild asthma. The main results of the present study are as follows: ) breathing gas mixtures containing 2% or 4% CO significantly attenuated bronchoconstrictor responses to methacholine, not differently in healthy subjects and subjects with mild asthma, and ) the causal inhibitory effect of CO was significantly mediated via an indirect effect of the increment of V̇e in response to intrapulmonary hypercapnia.
Topics: Airway Resistance; Asthma; Bronchoconstriction; Bronchoconstrictor Agents; Carbon Dioxide; Humans; Hypercapnia; Hyperventilation; Methacholine Chloride
PubMed: 35358399
DOI: 10.1152/japplphysiol.00763.2021 -
Archives of Dermatology Dec 1960
Topics: Dermatitis, Atopic; Eczema; Humans; Methacholine Chloride; Parasympatholytics
PubMed: 13693852
DOI: 10.1001/archderm.1960.01580060113018 -
Arerugi = [Allergy] Feb 2016In abroad, Methacholine Chloride (Provocholine®) is used to meet the indications of the diagnosis of bronchial airway hyperreactivity in subjects who do not have... (Clinical Trial)
Clinical Trial
BACKGROUND
In abroad, Methacholine Chloride (Provocholine®) is used to meet the indications of the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma. We examined efficacy, safety and pharmacokinetics of Methacholine Chloride (name of study drug: SK-1211) in order to get approved for the airway hyperresponsiveness test in Japan.
METHODS
Fifteen adult healthy volunteers, fifteen adult patients with asthma and ten pediatric patients with asthma were enrolled in this study. The airway hyperresponsiveness test with SK-1211 was conducted in accordance with Japanese Society of Allergology Standard Method.
RESULTS
When the threshold value of PC20 was 8 mg/mL, the sensitivity of adult patients with asthma was 66.7% (10/15 subjects) and the specificity of adult healthy volunteers was 86.7% (13/15 subjects). The sensitivity of pediatric patients with asthma was 70.0% (7/10 subjects). Not all subjects experienced some adverse reactions during inhalation of SK-1211, all of which were mild in severity and resolved soon with inhalation of a bronchodilator. There were no serious adverse reactions reported.
CONCLUSION
The airway hyperresponsiveness test with SK-1211 was no specific concern with safety and useful in the diagnosis of bronchial airway hyperresponsiveness.
Topics: Adolescent; Adult; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Child; Female; Humans; Male; Methacholine Chloride; Young Adult
PubMed: 26923652
DOI: 10.15036/arerugi.65.32 -
Annals of Allergy, Asthma & Immunology... Jul 2002
Topics: Bronchi; Bronchial Hyperreactivity; Forced Expiratory Volume; Humans; Methacholine Chloride
PubMed: 12141719
DOI: 10.1016/s1081-1206(10)61902-3 -
Contemporary Clinical Trials Apr 2018A planned change from Bricanyl® (terbutaline) Turbuhaler® M2 to M3 device required a pharmacodynamic study to evaluate therapeutic equivalence of the two devices.... (Randomized Controlled Trial)
Randomized Controlled Trial
A planned change from Bricanyl® (terbutaline) Turbuhaler® M2 to M3 device required a pharmacodynamic study to evaluate therapeutic equivalence of the two devices. Because of the flat dose-response curve for this type of agent over this dose range when assessing bronchodilation, a bronchoprotection study was considered more feasible. In this double-blind, double-dummy, multicentre, single-dose, two-factor, crossover study, patients with stable mild-to-moderate asthma were randomised to 0.5 or 1.5 mg terbutaline via Turbuhaler® M2 or Turbuhaler® M3 followed by a methacholine challenge test. Primary outcome variable: concentration of methacholine causing a 20% fall in FEV (PC). Pairwise contrasts were constructed with 95% CIs to determine assay sensitivity for M2 and M3 devices and therapeutic equivalence at each dose level (95% CI for M3:M2 devices within pre-specified limit [0.67-1.50]) and the relative dose-potency (RDP) between M3 and M2 determined with 90% CI. Sixty patients were randomised and all completed the study. Between-device ratios of PC (M3:M2) were 0.92 (95% CI: 0.75-1.13) for 0.5 mg and 0.88 (95% CI 0.72-1.08) for 1.5 mg and estimated RDP was 1.20 (0.96-1.53). In conclusion, a methacholine provocation study (PC primary variable) is a useful alternative to the standard bronchodilation study when assessing therapeutic equivalence of a bronchodilator.
Topics: Administration, Inhalation; Adult; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Nebulizers and Vaporizers; Outcome Assessment, Health Care; Therapeutic Equivalency
PubMed: 29474935
DOI: 10.1016/j.cct.2018.02.008 -
Respiratory Care Jan 2003Current American Thoracic Society and American Association for Respiratory Care guidelines for the delivery of aerosol agents such as methacholine chloride (MC) for...
BACKGROUND
Current American Thoracic Society and American Association for Respiratory Care guidelines for the delivery of aerosol agents such as methacholine chloride (MC) for bronchoprovocation testing require the use of pneumatic jet nebulizers that have well-defined droplet size and mass output. A recently developed disposable, breath-actuated nebulizer (AeroEclipse) may offer bronchoprovocation testers an alternative to existing devices.
METHODS
We studied the performance of 5 AeroEclipse nebulizers with regard to mass of MC delivered with various MC solution concentrations and numbers of inhalations, using a model of adult tidal breathing. Each nebulizer was operated with compressed air (8 L/min at 50 psig) and an initial fill of 2 mL. MC solutions with mass concentrations of 0.25, 0.98, 3.85, and 15.70 mg/mL were tested. The total mass of MC delivered was determined after 5, 10, and 15 complete breathing cycles, by assaying the MC collected on a filter placed at the nebulizer mouthpiece. The aerosol droplet size distribution, fine droplet fraction (FDF) (percentage of droplets < 4.8 microm diameter), and fine droplet mass (FDM) (mass of droplets < 4.8 microm diameter) were determined by laser diffractometry, using physiologically normal saline as a surrogate for MC solution.
RESULTS
The mean +/- SD FDM collected in 5 breathing cycles was 654 +/- 29 microg with the 15.70 mg/mL solution, 158 +/- 9 microg with the 3.85 mg/mL solution, 37 +/- 3 microg with the 0.98 mg/mL solution, and 7 +/- 2 microg with the 0.25 mg/mL solution. FDM showed a linear correlation (r(2) = 0.9999) with MC concentration, within the range studied. FDM also showed a linear correlation (r(2) = 0.999) with the number of breathing cycles. For instance, with the 15.70 mg/mL solution, FDM was 654 +/- 29 microg with 5 breathing cycles, 1,228 +/- 92 microg with 10 breathing cycles, and 1,876 +/- 132 microg with 15 breathing cycles.
CONCLUSIONS
Although the bronchoprovocation test procedure had to be slightly modified from the guidelines to accommodate the operation of the AeroEclipse's breath-actuation feature, our measurements indicate that a predictable dose of MC, within the useful range for bronchoprovocation testing, can be delivered to an adult patient breathing tidally. The green indicator on the AeroEclipse could be used to coach the patient to inhale for a specific period, thereby controlling MC delivery per breathing cycle.
Topics: Adult; Aerosols; Bronchial Provocation Tests; Bronchoconstrictor Agents; Disposable Equipment; Equipment Design; Humans; In Vitro Techniques; Methacholine Chloride; Nebulizers and Vaporizers; Particle Size
PubMed: 12556261
DOI: No ID Found