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Annals of the American Thoracic Society Mar 2015
Topics: Asthma; Bronchial Hyperreactivity; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride
PubMed: 25786145
DOI: 10.1513/AnnalsATS.201501-049ED -
Chest Oct 2008
Topics: Administration, Inhalation; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Forced Expiratory Volume; Humans; Methacholine Chloride; Nebulizers and Vaporizers
PubMed: 18842907
DOI: 10.1378/chest.08-1306 -
The European Respiratory Journal Apr 1998Methacholine chloride solutions, routinely used for testing bronchial hyperreactivity, have been shown to degrade over time. The data published addressing the optimal...
Methacholine chloride solutions, routinely used for testing bronchial hyperreactivity, have been shown to degrade over time. The data published addressing the optimal conditions for methacholine chloride storage are conflicting and incomplete. This study investigated the effects of a variety of conditions on the stability of methacholine chloride. Methacholine chloride, dissolved in phosphate buffered saline (PBS) or sodium chloride (NaCl) at 50 and 0.39 g x L(-1), was subjected to various light and temperature conditions for 9 months. Methacholine chloride degradation was determined by high performance liquid chromatography, and all solutions underwent bacterial and pH testing. By 9 months, all 50 g x L(-1) solutions of methacholine chloride had degraded by 65+/-0.8%. All 0.39 g x L(-1) solutions in NaCl had degraded by 11.0+/-0.33%. The 0.39 g x L(-1) solutions in PBS which had been frozen, refrigerated or stored at room temperature had degraded by 8.0%, 16.0+/-0.3% and 63.8+/-0.5%, respectively. The pH of methacholine chloride was 7.2 in PBS at 0.39 g x L(-1), 5.8 in PBS at 50 g x L(-1), 3.9 in NaCl at 0.39 and 2.7 in NaCl at 50 g x L(-1). Bacterial contamination was minimal. The results of this study demonstrate that methacholine chloride is more stable at the higher concentration. However, the pH of the more concentrated solutions of methacholine chloride in sodium chloride could cause bronchoconstriction in some subjects. We therefore recommend storing methacholine chloride at 50 g x L(-1) in phosphate-buffered saline.
Topics: Bronchoconstrictor Agents; Drug Stability; Drug Storage; Hydrogen-Ion Concentration; Methacholine Chloride; Sodium Chloride; Solutions; Time Factors
PubMed: 9623702
DOI: 10.1183/09031936.98.11040946 -
American Journal of Respiratory and... Oct 2018
Topics: Bronchial Provocation Tests; Humans; Methacholine Chloride; Nebulizers and Vaporizers; Societies, Medical
PubMed: 30160985
DOI: 10.1164/rccm.201805-0942ED -
The American Review of Respiratory... Oct 1982Methacholine inhalation challenge (MIC) has been shown to be an extremely useful diagnostic test. Because a decrease in the time and expense involved in the preparation...
Methacholine inhalation challenge (MIC) has been shown to be an extremely useful diagnostic test. Because a decrease in the time and expense involved in the preparation of methacholine chloride solutions might encourage more laboratories to perform MIC, we assessed the stability of several different concentrations of methacholine chloride in solution over a period of 4 months. We used and compared 2 different assay techniques: a high pressure liquid chromatography assay and a colorimetric assay. Comparable results were obtained by both assays and demonstrated that methacholine solutions stored either at room temperature or at 4 degrees C showed no significant decomposition over a period of 4 months. From our results, we conclude that: (1) methacholine chloride solutions are much more stable than stated in the Merck Manual, (2) the original data of MacDonald and coworkers on the stability of methacholine chloride solution are accurate, (3) our high pressure liquid chromatography method is an accurate and highly specific technique for measuring methacholine chloride solutions. The major clinical implication of our results is that the time and cost necessary to prepare methacholine chloride solutions is much less than previously thought. This should encourage a more widespread use of this important diagnostic technique for the demonstration of bronchial hyperreactivity.
Topics: Chromatography, High Pressure Liquid; Colorimetry; Drug Stability; Drug Storage; Methacholine Chloride; Methacholine Compounds
PubMed: 6751179
DOI: 10.1164/arrd.1982.126.4.717 -
Respiratory Medicine Mar 1998Methacholine chloride bronchoprovocation challenges are performed for the diagnosis and investigation of hyperreactive airways. Over the last 20 yrs various formulations...
Methacholine chloride bronchoprovocation challenges are performed for the diagnosis and investigation of hyperreactive airways. Over the last 20 yrs various formulations and pH values for the preparation of solutions of methacholine have been described. To determine the stability of methacholine chloride solutions prepared in a variety of buffers with differing pH values and under varying storage temperatures, we measured methacholine concentrations at intervals from 1 to 5 weeks. It was found that methacholine chloride solutions rapidly decompose if the pH is greater than 6 and that decomposition is more rapid as the pH is raised; solutions at pH 9, i.e. bicarbonate buffer, and stored at 27 degrees C have degradation up to 36% after only one week. Solutions of the same pH but prepared in different buffers can have both varied rates of deterioration and different absolute amounts of methacholine hydrolysed, e.g. solutions prepared in pH 9 borate buffer and stored at 27 degrees C have up to 60% degradation after 1 week. Solutions prepared in saline are stable probably because methacholine solutions are weakly acidic. The results emphasise the importance of preparing methacholine chloride in the proper buffers for use in the accurate assessment of airway responsiveness.
Topics: Bronchoconstrictor Agents; Drug Stability; Hydrogen-Ion Concentration; Methacholine Chloride
PubMed: 9692128
DOI: 10.1016/s0954-6111(98)90314-6 -
Methods in Molecular Biology (Clifton,... 2022Asthma has been the most prevalent chronic respiratory disease (Mensah et al. J Allergy Clin Immunol 142:744-748, 2018). To explore pathogenic mechanism or new...
Asthma has been the most prevalent chronic respiratory disease (Mensah et al. J Allergy Clin Immunol 142:744-748, 2018). To explore pathogenic mechanism or new treatments of asthma, mice have been utilized to model the disease. Eosinophilic airway inflammation, allergen specific-IgE, and airway hyperresponsiveness have been characteristic features of allergic asthma (Drake et al. Pulm Ther 5:103-115, 2019). In mouse models, airway hyperresponsiveness to inhaled broncho-constrictor agents such as methacholine chloride (MCh) has been a key disease marker (Alessandrini et al. Front Immunol 11:575936, 2020). A variety of systems to assess airway reactivity in mice are currently available. Here, three distinct systems are described as these have been used in many publications. In the first system, an invasive system in which mice are anesthetized and intubated followed by mechanical ventilation, lung resistance (R), dynamic compliance (C), and other respiratory parameters with MCh challenge are measured. In the second system, a noninvasive system equipped with a chamber in which mice can move freely and spontaneously breathe, changes in airways with MCh challenge are measured as enhanced pause (Penh) values. In the third system, in vitro airway smooth muscle (ASM) reactivity is monitored in an extracted mouse tracheal duct with a cholinergic agonist challenge or electrical stimulation. Each of these systems has unique features, benefits, or disadvantages.
Topics: Animals; Asthma; Bronchial Hyperreactivity; Disease Models, Animal; Eosinophilia; Immunoglobulin E; Methacholine Chloride; Mice; Mice, Inbred BALB C; Ovalbumin; Respiration Disorders; Respiratory Hypersensitivity
PubMed: 35771466
DOI: 10.1007/978-1-0716-2364-0_7 -
Journal of Clinical Pharmacy and... Oct 1999To investigate the stability of methacholine chloride in 0.9% sodium chloride solutions.
OBJECTIVE
To investigate the stability of methacholine chloride in 0.9% sodium chloride solutions.
METHOD
Methacholine powder was mixed with diluent to a final concentration of 5 and 10 mg/ml. Duplicates of each admixture were divided and stored in glass vials at 25 degrees C, 4 degrees C and -20 degrees C for 12 months. At appropriate times intervals, samples were removed from solutions and analysed. Methacholine concentrations were measured using a high performance capillary electrophoresis assay.
RESULTS
No colour or other visual changes were seen in any sample. However, an additional peak was observed in some samples.
CONCLUSION
Methacholine chloride solutions 5 mg/ml were stable in isotonic sodium chloride after refrigeration or freezing over a period of one year; methacholine chloride solutions 10 mg/ml were stable for one year after freezing. The solutions stored at ambient temperature were stable for 35 days and for less than 14 days, respectively, for the 5 and the 10 mg/ml solutions.
Topics: Bronchoconstrictor Agents; Cold Temperature; Drug Stability; Drug Storage; Electrophoresis, Capillary; Freezing; Isotonic Solutions; Methacholine Chloride; Reproducibility of Results; Sodium Chloride; Time Factors
PubMed: 10583699
DOI: 10.1046/j.1365-2710.1999.00237.x -
Thorax Mar 1995A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic...
A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic agents are known to induce headaches but the mechanism remains unclear. Vascular factors could be implicated.
Topics: Adult; Allied Health Personnel; Bronchial Provocation Tests; Female; Headache; Humans; Methacholine Chloride; Occupational Diseases; Occupational Exposure
PubMed: 7660351
DOI: 10.1136/thx.50.3.319 -
The American Review of Respiratory... Mar 1983Persons with hyperreactive airways differ quantitatively from normal persons in their response to bronchial provocation testing with methacholine chloride (Mch)....
Persons with hyperreactive airways differ quantitatively from normal persons in their response to bronchial provocation testing with methacholine chloride (Mch). Methacholine chloride has strong hygroscopic properties that necessitate careful dessication, preparation, and handling if accurate results are to be achieved. The rate of hydration of Mch was determined by exposing the drug to various levels of relative humidity. The rate of water uptake was directly related to the availability of water in the atmosphere. At 49% relative humidity, a 0.125%/min gain in weight was noted, which increased to 0.489%/min at 80% relative humidity. Adequate dessication time and technique were determined by noting the time required to return the drug from a hydrated to a dry state. With proper technique, dessication was virtually complete by 4 to 6 h, and 20 to 24 h assured a return to the dry state. From these data, guidelines for preparation and handling of Mch test solutions can be formulated.
Topics: Bronchial Provocation Tests; Desiccation; Humans; Humidity; Methacholine Chloride; Methacholine Compounds
PubMed: 6338784
DOI: 10.1164/arrd.1983.127.3.350