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Journal of Applied Physiology... May 2011Adenosine 5'-monophosphate (AMP) and methacholine are commonly used to assess airway hyperreactivity. However, it is not fully known whether the site of airway... (Comparative Study)
Comparative Study
Adenosine 5'-monophosphate (AMP) and methacholine are commonly used to assess airway hyperreactivity. However, it is not fully known whether the site of airway constriction primarily involved during challenges with either agent is similar. Using a ventilation distribution test, we investigated whether the constriction induced by each agent involves the lung periphery in a similar fashion. Ventilation distribution was evaluated by the phase III slope (S) of the single-breath washout, using gases with different diffusivities like helium (He) and hexafluorosulfur (SF(6)). A greater postchallenge increase in S(He) reflects alterations at the level of terminal and respiratory bronchioles, while a greater increase in S(SF6) reflects alterations in alveolar ducts, increases to an equal extent reflecting alterations in more proximal airways where gas transport is still convective for both gases. S(SF6) and S(He) were measured in 15 asthma patients before and after airway challenges (20% forced expired volume in 1-s fall) with AMP and methacholine. S(He) increased to a greater extent than S(SF6) after AMP challenge (5.7 vs. 3.7%/l; P = 0.002), with both slopes increasing to an equal extent after methacholine challenge (3.1%/l; P = 0.959). The larger increase in S(He) following AMP challenge suggests distal ventilation impairment up to the level of terminal and respiratory bronchioles. With methacholine, the similar increases in S(He) and S(SF6) suggest a less distal impairment. AMP, therefore, seems to affect more extensively the very peripheral airways, whereas methacholine seems to have an effect on less distal airways.
Topics: Adenosine Monophosphate; Adult; Asthma; Female; Humans; Lung; Male; Methacholine Chloride; Pulmonary Ventilation; Respiratory Function Tests
PubMed: 21393472
DOI: 10.1152/japplphysiol.01401.2010 -
Chest Apr 1994Methacholine, provided by industrial sources, has traditionally been used in studies of airways responsiveness. In 1986, a Food and Drug Administration approved... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Methacholine, provided by industrial sources, has traditionally been used in studies of airways responsiveness. In 1986, a Food and Drug Administration approved formulation of methacholine (Provocholine) was released and replaced industrial methacholine in many pulmonary laboratories. To determine whether methacholine and Provocholine cause an equivalent degree of bronchoconstriction, a double blind, cross-over clinical trial was undertaken. After randomization, 19 medicine residents and respiratory therapists each performed methacholine challenge testing using either methacholine or Provocholine. Forty-eight hours later, each participant returned for repeat challenge testing with the alternate agent. The log of the dose-response slope (logslope) was calculated for each test. The mean logslope with methacholine (-0.15 +/- 1.84) and with Provocholine (-0.26 +/- 1.57) did not differ (paired Student's t test, p = 0.64). Further, excellent agreement was found between each subject's logslope with methacholine and with Provocholine (intraclass correlation coefficient rI = 0.82). Proton beam nuclear magnetic resonance revealed no structural differences between the two compounds. These findings suggest that methacholine from industrial sources and Provocholine are clinically and structurally similar and that the two agents may be used interchangeably in nonspecific bronchial provocation testing.
Topics: Adult; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Magnetic Resonance Spectroscopy; Male; Methacholine Chloride
PubMed: 8162731
DOI: 10.1378/chest.105.4.1095 -
Respiratory Medicine Jul 1994
Topics: Adult; Bronchi; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Reproducibility of Results
PubMed: 7938800
DOI: 10.1016/s0954-6111(05)80052-6 -
The Journal of Asthma : Official... Jun 2017The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical...
Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.
OBJECTIVES
The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers.
METHODS
Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test.
RESULTS
Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04.
CONCLUSIONS
Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.
Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Sectional Studies; Female; Humans; Inflammation; Inflammation Mediators; Male; Mannitol; Methacholine Chloride; Middle Aged; Nitric Oxide; Respiratory Function Tests; Sensitivity and Specificity; Severity of Illness Index; Skin Tests
PubMed: 27686218
DOI: 10.1080/02770903.2016.1238926 -
Zhonghua Yi Xue Za Zhi = Chinese... Dec 1997The bronchodilator agent is an important drug for patients with chronic obstructive pulmonary disease. Methacholine is a popular bronchial provocative agent. Although...
BACKGROUND
The bronchodilator agent is an important drug for patients with chronic obstructive pulmonary disease. Methacholine is a popular bronchial provocative agent. Although the major acting site of bronchodilator, methacholine and upper respiratory tract infection (URI) has been evaluated in some studies, the sites are still in debate. This study investigated the exact major acting sites.
METHODS
Thirty subjects participated in this study. Episodes of URI were identified by a questionnaire. Spirometry, bronchial provocative test with methacholine, and five minutes' inhalation of a mixture of helium and oxygen (HeO2) were done on day one. Spirometry, bronchodilator test, with five minutes' inhalation of HeO2 and expiratory flow-volume (F-V) curve were performed on another day. The change of pre- and post-HeO2 VEMax50 was calculated as delta VEMax50. The pre- and post-bronchodilator VEMax50 and delta VEMax50 differences were counted to decide the acting site of bronchodilator. After bronchial provocative test with methacholine, the volume of isoflow (VisoV) was estimated from pre- and post-HeO2 F-V curve to establish the acting site of methacholine.
RESULTS
This study indicated that small airways are the major acting sites of bronchodilators, large airways are the major acting sites of methacholine and URI affects mainly large airways. Although airway hyperresponsiveness is more severe in subjects with positive methacholine response, the recovery of spirometry values is not significantly different between the methacholine-positive and -negative groups.
CONCLUSIONS
The major acting sites of the bronchodilator, methacholine, and URI are the small, large and large airways, respectively. Bronchial hyperresponsiveness is not a cause of quick restoration of spirometry values in subjects with positive methacholine response.
Topics: Adolescent; Adult; Aged; Bronchial Hyperreactivity; Bronchodilator Agents; Female; Humans; Male; Methacholine Chloride; Middle Aged; Respiratory Physiological Phenomena; Respiratory System; Respiratory Tract Infections; Sympathomimetics
PubMed: 9531735
DOI: No ID Found -
Respiration; International Review of... 2005The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard gas. Pulmonary complications as a result of this gas range from severe...
BACKGROUND
The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard gas. Pulmonary complications as a result of this gas range from severe bronchial stenosis to mild or no symptoms. Airway hyperresponsiveness (AHR) which is usually assessed as response to inhaled methacholine is the most characteristic feature of asthma. AHR is reported in chronic obstructive pulmonary disease patients and smokers, and may also show in chemical warfare victims. However, there are little reports regarding AHR in chemical warfare victims.
OBJECTIVE
Therefore, in this study, airway responsiveness to methacholine in victims of chemical warfare was examined.
METHODS
The threshold concentrations of inhaled methacholine required for a 20% change in forced expiratory flow in 1 s (FEV1; PC20) or a 35% change in specific airway conductance (PC35) were measured in 15 chemical war victims and 15 normal control subjects.
RESULTS
In 10 out of 15 chemical warfare victims (two thirds), PC20 and PC35 methacholine could be measured and subjects were called responders. AHR to methacholine in responder chemical war victims (PC20 = 0.41 and PC35 = 0.82 g/l) was significantly lower than in normal subjects (PC20 = 5.69 and PC35 = 4.60 g/l, p < 0.001 for both cases). There was a significant correlation between FEV1 and PC20 methacholine (r = 0.688, p < 0.001). The correlations between PC20 and PC35 were statistically significant as well (r = 0.856, p < 0.001).
CONCLUSION
Results showed increased airway responsiveness of most chemical warfare victims to methacholine which correlated with the FEV1 value and which may be related to chronic airway inflammation or irreversible airway changes.
Topics: Adult; Bronchi; Bronchial Provocation Tests; Bronchoconstrictor Agents; Case-Control Studies; Chemical Warfare Agents; Forced Expiratory Volume; Humans; Inhalation Exposure; Male; Methacholine Chloride; Middle Aged; Mustard Gas; Veterans
PubMed: 15988169
DOI: 10.1159/000086719 -
International Journal of Medical... 2023Histamine receptor-1 (H) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may...
Histamine receptor-1 (H) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10 M or more caused a slight relaxation in response to methacholine's 10 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.
Topics: Rats; Humans; Animals; Methacholine Chloride; Menthol; Cetirizine; Muscle, Smooth; Muscle Contraction; Trachea
PubMed: 37928871
DOI: 10.7150/ijms.86769 -
Respirology (Carlton, Vic.) Mar 1999It is well recognized that bronchial responsiveness to methacholine is reduced after methacholine-induced bronchoconstriction in non-asthmatic subjects, but not in... (Clinical Trial)
Clinical Trial
It is well recognized that bronchial responsiveness to methacholine is reduced after methacholine-induced bronchoconstriction in non-asthmatic subjects, but not in asthmatic subjects. However, it is unknown how long the methacholine tachyphylaxis lasts. The present study was conducted to elucidate duration of the methacholine tachyphylaxis in healthy non-asthmatic subjects. Measurements of methacholine responsiveness were repeated six times at intervals of 1 h and 1, 2, 3 and 7 days in eight healthy non-asthmatic young female subjects in whom methacholine concentrations causing a 20% fall in forced expiratory volume in 1 sec (FEV1; PC20-Meth) were 40 mg/mL or less. Geometric mean value (GSEM) of PC20-Meth was 10.6 (1.44) mg/mL at the first challenge, 63.4 (1.85) at the 1-h interval, 50.2 (1.67) at the 1-day interval, 49.7 (1.68) at the 2-day interval, 17.3 (1.51) at the 3-day interval and 13.1 (1.44) mg/mL at the 7-day interval. The values at intervals of 1 h to 3 days were significantly greater than the initial value. These results indicate that measurements of methacholine responsiveness should be separated by at least 7 days to avoid the tachyphylaxis when the tests are repeated in non-asthmatic subjects.
Topics: Adult; Bronchial Provocation Tests; Bronchoconstrictor Agents; Female; Forced Expiratory Volume; Humans; Methacholine Chloride; Statistics, Nonparametric; Tachyphylaxis; Time Factors
PubMed: 10339730
DOI: 10.1046/j.1440-1843.1999.00151.x -
Medicine and Science in Sports and... Oct 2007Asthma is frequently reported in endurance athletes, particularly in cross-country skiers. It has been reported that an exercise field test performed with the... (Comparative Study)
Comparative Study
INTRODUCTION
Asthma is frequently reported in endurance athletes, particularly in cross-country skiers. It has been reported that an exercise field test performed with the competitive type of exercise is the better for diagnosing asthma and bronchial hyperresponsiveness in athletes than bronchial provocation with methacholine.
OBJECTIVE
The main objective was to compare an exercise field test consisting of a skiing competition with methacholine bronchial provocation in the diagnosis of asthma and bronchial hyperresponsiveness among skiers.
METHODS
Twenty-four elite cross-country skiers from the Norwegian national teams (males/females = 16/8) were included in the study. The cumulative dose of inhaled methacholine causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PD20) was compared with reduction in lung function (FEV1) >or= 10% from before to after an exercise field test consisting of a cross-country skiing competition, 10 km (males) and 7 km (females), respectively.
RESULTS
Nine out of 24 (37.5%) athletes experienced a positive methacholine test (PD20 < 8 micromol) (2 females and 7 males), whereas only 2 of the 24 subjects (8.3%) had reductions in FEV1 >or= 10% after the exercise field test. A significant negative correlation was found between age and bronchial responsiveness, r = -0.47, P = 0.02.
CONCLUSION
The methacholine bronchial provocation test is more sensitive than a sport specific exercise field test for identifying athletes with asthma and/or bronchial hyperresponsiveness.
Topics: Adult; Asthma; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Exhalation; Female; Humans; Male; Methacholine Chloride; Norway; Skiing
PubMed: 17909392
DOI: 10.1249/mss.0b013e31813738ac -
Chest Oct 2003The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine... (Comparative Study)
Comparative Study
BACKGROUND
The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded.
OBJECTIVE
To develop a method with reduced methacholine waste and to compare it to the standard method.
METHODS
Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation.
RESULTS
There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification.
CONCLUSION
The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.
Topics: Adult; Asthma; Bronchial Provocation Tests; Female; Humans; Male; Methacholine Chloride; Middle Aged
PubMed: 14555588
DOI: 10.1378/chest.124.4.1522