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Diagnostic tests in respiratory medicine
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Methacholine provocation works directly on the smooth muscles, whereas histamine acts via nervous irritant receptors and a vagal reflex. Nevertheless, they give similar results; in practical terms, there is little reason for choosing one over the other test method. Side effects of histamine, such as throat irritation, hoarseness, cough, flushing and headache at high doses, occur frequently, whereas no side effects of methacholine have been reported. Therefore, most direct tests are performed with methacholine. There is no standardised test method; there are several methods to be used when performing direct bronchial challenge testing. Furthermore, methacholine has a short storage time, lasting only 1 month after opening the bottle. A positive response of 20% reduction in FEV1 (i.e. cut-off value of 80% in FEV1) should be calculated before testing to know when to stop the test.
Pulmonary diseases in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Leah Lande, Abraham Sanders, Dana Zappetti
The diagnosis of asthma is made based on the clinical history as noted above with or without supporting physical exam findings of expiratory wheezing or rhonchi. The diagnosis is confirmed by spirometry demonstrating a reduced forced expiratory volume in one second (FEV1) with a reduced ratio of FEV1 to FVC, with further confirmation if airway reversibility is shown by an improvement by 12% and 200cc in either the FEV1 or the FVC after the administration of an inhaled bronchodilator. The sensitivity, however, of spirometry in the diagnosis of asthma is limited (18). Methacholine challenge testing, which can be used to diagnose asthma in patients with normal spirometry, is contraindicated in pregnant women due to a lack of safety data (19).
Common Office Tests and Procedures for the Allergist
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Procedure. Methacholine is the agent of choice for nonspecific bronchoprovocation challenge testing. It is FDA-approved and available in 100 mg vials as a dry powder. Normal saline is the recommended diluent. There are different published dilution schemes that depend on the dosing protocol used. Both two-minute tidal breathing and five-breath dosimeter protocols are available. The reader is referred to the ATS guidelines for specifics on dilutions and dosing schemes (Crapo et al. 2000). In general, a baseline spirometry is obtained. If the baseline FEV1 is < 60%, albuterol is administered and the spirometry is repeated. The first dose of methacholine is given, followed by spirometry at the appropriate time interval. If the drop in FEV1 is < 20% from the baseline, the testing proceeds to the next dose. If at any point the change in FEV1 is > 20% from baseline, testing is stopped, signs and symptoms are recorded, albuterol is given and spirometry is performed 10 minutes later. If the highest dose of methacholine is given and the decline in FEV1 is < 20% from baseline, the test is complete. A sample methacholine challenge test report form is available in Appendix C of the ATS guidelines (Crapo et al. 2000).
Practical approaches to the diagnosis of asthma in school-age children
Published in Expert Review of Respiratory Medicine, 2022
Pooja Devani, David K H Lo, Erol A Gaillard
During a direct bronchial challenge test, the chemical compound inhaled at increasing concentrations during the challenge directly interacts with receptors in the airways. Methacholine, for example, mimics the neurotransmitter acetylcholine and interacts with the muscarinic M3 receptor present on airway smooth muscle. Direct bronchial challenge tests are useful tests to rule out asthma. Indirect bronchial challenge tests are more specific and good tests to confirm the diagnosis of asthma but have low sensitivity. Indirect bronchial challenge tests such as exercise testing and inhaled dry powder mannitol challenge testing exert their effects on the bronchi by creating osmolar changes in the airway epithelium. Exercise causes the airways to dry and cool resulting in water loss and osmolar change at the level of the airway epithelium. Dry powder, mannitol increases the osmolarity of the bronchial mucosa triggering the release of mediators from mast cells and eosinophils including histamine, prostaglandins and leukotrienes. Indirect bronchial challenge tests are more specific but have low sensitivity to diagnose asthma [35].
Utility and efficiency of methacholine challenge testing in evaluating pediatric asthma: unraveling the diagnostic conundrum
Published in Journal of Asthma, 2021
Rajeev Bhatia, Kelly J. DiLullo
Subjects with exercise symptoms only were less likely to be positive on MCT in our sample population. Methacholine directly interacts with muscarinic receptors on airway smooth muscle, resulting in contraction and airway narrowing. Therefore, it is considered a direct challenge test along with histamine. Both exercise and eucapnic hyperventilation cause airway drying and cooling, which leads to bronchoconstriction through an osmolar change in the airway epithelium resulting from water loss. Those are examples of indirect challenge tests. Individuals may respond differently to direct and indirect challenge tests based on what stimuli are involved in clinical symptoms. Since exercise triggers bronchoconstriction through an inflammatory mechanism instead of direct stimulation, the likelihood of false negative MCT is high in subjects with exercise-induced symptoms only (14). Anderson et al. performed MCT and exercise challenge testing in subjects with clinical asthma across 25 sites in the USA to compare MCT and exercise challenge testing results in the same population. Similar to our findings, they showed that 45% of subjects (73/163) with positive exercise test had negative MCT results (15). With this information in mind, the efficiency of MCT can be increased in the future by carefully choosing patients who are referred for the test. For patients with only exercise-induced symptoms, indirect challenge tests like exercise challenge test or cardiopulmonary exercise testing may be more effective in establishing the diagnosis (16).
Post-treatment with a heat shock protein 90 inhibitor prevents chronic lung injury and pulmonary fibrosis, following acute exposure of mice to HCl
Published in Experimental Lung Research, 2020
Margarita Marinova, Pavel Solopov, Christiana Dimitropoulou, Ruben M. L. Colunga Biancatelli, John D. Catravas
Following acid instillation, we observed pathological changes in lung respiratory mechanics and airway hyperresponsiveness. Total respiratory system resistance and elastance, as well as Newtonian resistance and tissue damping increased significantly in HCl-treated mice, both at baseline and following a methacholine challenge (Figure 5a–d). Methacholine is a strong bronchoconstrictor agent widely used to evaluate airway hyper-reactivity.9,28 Airway hyperreactivity was virtually abolished in mice treated with AUY-922 (Figure 5a–d). We also computed pressure-volume relationships and static compliance (Cst). A significant shift to the right in pressure-volume loops and decrease in Cst was observed in HCl exposed mice. Taken together, these results once again indicate a decrease in lung dynamic and static compliance (the reciprocal of elastance), increase in pulmonary air flow resistance, bronchial hyper-responsiveness and an overall pattern of chronic inflammation and restrictive lung disease, similar to what is observed in human subjects affected by pulmonary fibrosis. Treatment with AUY-922, for either 15 or 30 days, completely prevented loss of compliance and lung stiffness, as reflected in control-like pressure-volume curves and Cst values (Figure 5e,f). Moreover, there was a significant positive correlation between collagen protein expression and baseline total respiratory system elastance (Figure 6).