-
The Clinical Respiratory Journal Aug 2021The American Thoracic Society (ATS) guideline for methacholine challenge testing (MCT) recommended using the English Wright (EW) nebuliser. However, other brands of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The American Thoracic Society (ATS) guideline for methacholine challenge testing (MCT) recommended using the English Wright (EW) nebuliser. However, other brands of nebulisers are also indicated to be acceptable for this technique, but further validation of nebuliser performance is recommended.
OBJECTIVE
To compare the methacholine provocation concentration causing a 20% fall in forced expiratory volume in 1 second (PC -FEV ) measured by using EW nebuliser and DV 646 nebuliser.
METHODS
Subjects were randomly assigned to undergo 2-min tidal breathing methacholine challenge with either EW or DV 646 nebuliser on two separate days, which were at least 24 hours but not more than 7 days apart. The above procedure was repeated for each subject in 1 month, but the nebulisers were selected in a reverse order.
RESULTS
The study includes 15 mild and stable asthmatic patients. The geometric means (SD) of methacholine PC measured with using EW and DV 646 nebulisers were 1.82 (6.38) mg/mL versus 0.83 (1.82) mg/mL, respectively in the initial two visits and 2.56 (6.29) mg/mL versus 0.78 (1.40) mg/mL in the following two visits (both P < 0.05). There are well correlations between PC20-EW1 and PC20-EW2 (r = 0.99, P < 0.01), PC20-DV1 and PC20-DV2 (r = 0.88, P < 0.01), and between PC20-EW1 and PC20-DV1 (r = 0.91, P < 0.01), PC20-EW2 and PC20-DV2 (r = 0.78, P < 0.01).
CONCLUSIONS
PC -FEV measured by using the two conventional jet nebulisers was both repeatable and the results were highly correlated.
Topics: Asthma; Bronchial Provocation Tests; Forced Expiratory Volume; Humans; Methacholine Chloride; Nebulizers and Vaporizers
PubMed: 33840150
DOI: 10.1111/crj.13374 -
The Journal of Allergy and Clinical... 2017Airway hyperresponsiveness is a characteristic feature of asthma, and its measurement is an important tool in its diagnosis. With a few caveats, methacholine bronchial... (Review)
Review
Airway hyperresponsiveness is a characteristic feature of asthma, and its measurement is an important tool in its diagnosis. With a few caveats, methacholine bronchial provocation by a 2-minute tidal breathing method is highly sensitive; a negative test result (PC > 16 mg/mL, PD > 400 μg) rules out current asthma with reasonable certainty. A PC value of less than 1 mg/mL/PD value of less than 25 μg is highly specific (ie, diagnostic) but quite insensitive for asthma. For accurate interpretation of the test results, it is important to control and standardize technical factors that have an impact on nebulizer performance. In addition to its utility to relate symptoms such as cough, wheeze, and shortness of breath to variable airflow obstruction (ie, to diagnose current asthma), the test is useful to make a number of other clinical assessments. These include (1) evaluation of patients with occupational asthma, (2) evaluation of patients with exercise-induced respiratory symptoms, (3) evaluation of novel asthma medications, (4) evaluation of relative potency of inhaled bronchodilators, (5) as a biomarker to adjust anti-inflammatory therapy to improve clinical outcomes, and (6) in the evaluation of patients with severe asthma to rule out masqueraders such as laryngeal dysfunction. The actual mechanism of altered smooth muscle behavior in asthma that is assessed by direct (eg, methacholine) or indirect (eg, allergen) bronchial provocation remains one of the most fundamental questions related to asthma that needs to be determined. The test is underutilized in clinical practice.
Topics: Animals; Asthma; Bronchial Provocation Tests; Bronchial Spasm; Forced Expiratory Volume; Humans; Methacholine Chloride; Muscle, Smooth; Nebulizers and Vaporizers; Respiratory Hypersensitivity
PubMed: 28163029
DOI: 10.1016/j.jaip.2016.11.030 -
Respiratory Physiology & Neurobiology Oct 2021Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in...
Balb/c mice respiratory mechanics was studied in two intravenous methacholine (MCh) protocols: bolus and continuous infusion. The Constant Phase Model (CPM) was used in this study. The harmonic distortion index (k) was used to assess the respiratory system nonlinearity. The analysis of variance showed difference between groups (OVA vs control) and among doses for both protocols. Bolus protocol posttest: there was a difference between OVA and control at 0.3 and 1 mg/kg doses (p<0.0001 and p<0.001) for R. Infusion: there was a difference between OVA and control at 192 μg.kg.min dose for R, G and H, (p<0.01; p<0.001; p<0.001). An increment was found in k values near to the observed peak values in bolus protocol. The bolus protocol could better differentiate inflamed and non-inflamed airway resistance, whereas the differences between OVA and control in continuous infusion protocol were associated to airway- and, mainly, parenchyma-related parameters. Moreover, the bolus protocol presented a higher nonlinear degree compared to the infusion protocol.
Topics: Animals; Asthma; Bronchoconstrictor Agents; Disease Models, Animal; Male; Methacholine Chloride; Mice; Mice, Inbred BALB C; Models, Theoretical; Respiratory Mechanics
PubMed: 34062282
DOI: 10.1016/j.resp.2021.103705 -
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 -
Allergy Mar 2023Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The...
BACKGROUND
Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLD , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma.
METHODS
Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLD response and compared between groups.
RESULTS
Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLD slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLD (respectively) throughout methacholine testing, were also observed.
CONCLUSION
In addition to baseline differences, small-airway responsiveness (as represented by the change in MLD ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.
Topics: Humans; Female; Methacholine Chloride; Asthma; Bronchoconstriction; Bronchial Provocation Tests; Obesity; Forced Expiratory Volume
PubMed: 36070075
DOI: 10.1111/all.15509 -
Occupational Medicine (Oxford, England) Nov 2018Bronchial hyper-responsiveness (BHR) is often regarded as a 'hallmark' of asthma, and bronchoprovocation testing is frequently performed to support a diagnosis of...
BACKGROUND
Bronchial hyper-responsiveness (BHR) is often regarded as a 'hallmark' of asthma, and bronchoprovocation testing is frequently performed to support a diagnosis of asthma. The European Respiratory Society (ERS) and American Thoracic Society (ATS) have recently updated their technical standards and guidelines for performing methacholine challenge testing (MCT), the most commonly performed clinical test of BHR.
AIMS
To review the updated guidelines and discuss the various changes and their potential impact on clinicians.
METHODS
We performed a systematic review of references identified using Medline and hand searches of identified articles.
RESULTS
The new ERS and ATS guidelines recommend that MCT be performed using tidal breathing, not deep inspirations with breath holding, that results be reported as the PD20 (cumulative dose causing a 20% fall in forced expiratory volume in 1 s [FEV1]), rather than PC20 (concentration causing a 20% fall in FEV1), and that manufacturers of nebulizers and other delivery systems provide performance characteristics to allow calculation of PD20 values. Our preliminary survey found that the new guidelines are only slowly being adopted.
CONCLUSIONS
Clinicians should be aware that recommended BHR testing methods, particularly for MCT, have changed. As a result, they should anticipate that test outcomes will increasingly be reported in terms of PD20, which will facilitate longitudinal assessment of their patients. Compliance with the new guidelines will increase the sensitivity of MCT in mild and asymptomatic asthmatics.
Topics: Adult; Asthma; Bronchi; Bronchial Provocation Tests; Bronchoconstrictor Agents; Female; Humans; Male; Methacholine Chloride; Nebulizers and Vaporizers; Total Lung Capacity
PubMed: 30192977
DOI: 10.1093/occmed/kqy122 -
Chest Apr 2023The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
BACKGROUND
The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
RESEARCH QUESTION
Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?
STUDY DESIGN AND METHODS
Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry.
RESULTS
Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m in control subjects and 47.2 ± 8.2 kg/m in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm HO/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm HO/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group.
INTERPRETATION
Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.
Topics: Female; Humans; Methacholine Chloride; Cross-Sectional Studies; Asthma; Respiratory System; Spirometry; Bronchial Provocation Tests; Obesity; Airway Resistance; Forced Expiratory Volume
PubMed: 36610669
DOI: 10.1016/j.chest.2022.12.030 -
The Journal of Allergy and Clinical... 2017The assessment of airway responsiveness and inflammation is key to the investigation of occupational asthma (OA).
BACKGROUND
The assessment of airway responsiveness and inflammation is key to the investigation of occupational asthma (OA).
OBJECTIVE
We sought to assess and compare the diagnostic accuracies of the blood and sputum eosinophil counts and the methacholine challenge for the diagnosis of OA.
METHODS
We conducted a retrospective study assessing 618 patients who underwent specific inhalation challenges (SICs) for symptoms suggestive of OA between 2000 and 2015. A sputum induction and a methacholine challenge were performed before and after SICs. Blood samples were collected in all subjects before the SICs and in 100 subjects before and after SICs. The diagnostic accuracies of blood and sputum eosinophil counts and methacholine challenge were calculated for diagnosing OA.
RESULTS
The change in blood eosinophil count failed to differentiate workers with positive and negative SICs. The change in sputum eosinophil counts induced by the exposure to the offending agent had the highest diagnostic accuracy (receiver operating characteristic area under the curve: 86% [95% confidence interval: 0.8-0.9, P < .001]) for diagnosing OA compared with changes in concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 second (PC) and blood eosinophils. Combining a 2-fold or greater decrease in PC or a 3% or greater increase in sputum eosinophil count achieved a sensitivity of 84% and a specificity of 74% with a negative predictive value of 91% for the diagnosis of OA.
CONCLUSIONS
Blood eosinophil counts do not appear to be an effective aid for diagnosing OA. The performance of both sputum cell count analysis and a methacholine challenge before and after exposure to the offending agent may represent an effective alternative in diagnosing OA when SICs are unavailable.
Topics: Adult; Allergens; Asthma, Occupational; Biomarkers; Blood Cells; Bronchial Provocation Tests; Cell Count; Eosinophils; Female; Humans; Inflammation; Male; Methacholine Chloride; Middle Aged; Predictive Value of Tests; Prognosis; Retrospective Studies; Sensitivity and Specificity; Spirometry; Sputum
PubMed: 28286155
DOI: 10.1016/j.jaip.2017.02.001 -
Experimental Physiology Apr 2017What is the central question of this study? The parasternal intercostal electromyogram (EMGpara) is known to provide an accurate, non-invasive index of respiratory...
What is the central question of this study? The parasternal intercostal electromyogram (EMGpara) is known to provide an accurate, non-invasive index of respiratory load-capacity balance. Although relationships between EMGpara and both airflow obstruction and hyperinflation have been shown, the independent contribution of each factor has not been examined. What is the main finding and its importance? Reductions in airway calibre and inspiratory capacity along with increases in EMGpara were induced via methacholine challenge. A strong inverse relationship was observed between EMGpara and airway obstruction, with no influence of inspiratory capacity. These data suggest that EMGpara is more strongly influenced by airway calibre than by changes in end-expiratory lung volume during airway challenge testing. Neural respiratory drive, measured via the parasternal intercostal electromyogram (EMGpara), provides a non-invasive index of the load-capacity balance of the respiratory muscle pump. Previous studies in patients with obstructive lung disease have shown strong relationships between EMGpara and the extent of both airflow obstruction and hyperinflation. The relative influence of the two factors has not, however, been described. Airflow obstruction was induced via methacholine challenge testing in 25 adult humans. Forced expiratory volume in 1 s (FEV ) and surface EMGpara during tidal breathing were measured after each dose, with 20 of the participants also undergoing measurements of inspiratory capacity (IC) at each stage. Linear mixed model analysis was used to assess dose-wise changes in FEV and EMGpara, and thereafter to determine the influence of changes in FEV and IC on change in EMGpara. Median (interquartile range) FEV decreased significantly [from 96.00 (80.00-122.30) to 67.80 (37.98-92.27)% predicted, P < 0.0001] and EMGpara increased significantly [from 5.37 (2.25-8.92) to 6.27 (3.37-19.60) μV, P < 0.0001] from baseline to end of test. Linear mixed model analysis showed a significant interaction between methacholine dose and induced change in EMGpara, with an increase in EMGpara of 0.24 (95% confidence interval 0.11-0.37) μV per methacholine dose . Change in FEV further influenced this relationship [increase in slope of 0.002 (0.004-0.001) μV dose per % predicted fall in FEV , P = 0.011], but not with change in IC. These data suggest that bronchoconstriction exerts a more potent influence on levels of EMGpara than changes in end-expiratory lung volume during methacholine challenge.
Topics: Adult; Bronchial Provocation Tests; Bronchoconstriction; Female; Forced Expiratory Volume; Humans; Inspiratory Capacity; Intercostal Muscles; Lung; Lung Volume Measurements; Male; Methacholine Chloride; Respiratory Muscles; Tidal Volume; Young Adult
PubMed: 28194830
DOI: 10.1113/EP086120 -
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