I. Purpose and Scope II. Methacholine Challenge Testing A. Indications B. Contraindications C. Technician Training/Qualifications D. Safety E. Patient Preparation F. Choice and Preparation of Methacholine G. Dosing Protocols 1. Two-Minute Tidal Breathing Dosing Protocol 2. Five-Breath Dosimeter Protocol H. Nebulizers and Dosimeters I. Spirometry and Other End-point Measures J. Data Presentation K. Interpretation III. Exercise Challenge A. Indications B. Contraindications and Patient Preparation C. Exercise Challenge Testing D. Assessing the Response References Appendix A: Sample Methacholine Challenge Test Consent Form Appendix B: Sample Methacholine Challenge Pretest Questionnaire Appendix C: Sample Report Format Appendix D: Equipment Sources

Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.

An easy and safe dose-response histamine-inhalation test is described, to measure the level of non-specific bronchial reactivity. The test was performed in 307 subject. Non-specific bronchial reactivity was increased in 3% of presumed normal subjects, in 100% of active asthmatics and in 69% of asymptomatic asthmatics with previous symptoms only at times of exposure to clinically relevant allergens. It was also increased in 47% of patients with cough and no other chest symptoms, in 40% of patients with rhinitis and vague chest symptoms not by themselves diagnostic of asthma, and in 22% of patients with rhinitis and no chest symptoms. The patients with asthma were studied when their asthma was well controlled and when their minimum drug requirements had been established. The mean level of bronchial reactivity increased with increasing minimum drug requirements. The level of bronchial reactivity also showed a strong negative correlation with the forced expiratory volume in 1 sec (FEV1). Atopic subjects, with or without asthma, showed a significant positive correlation between the level of bronchial reactivity and atopic status as indicated by the number of positive allergy skin tests.

Bronchial reactivity to inhaled histamine: a method and clinical survey.

We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Damage of the airway epithelium and bronchial reactivity in patients with asthma.

1. Damage of the Airway Epithelium and Bronchial : Reactivity in Patients with Asthma

Airway eosinophilia, epithelial desquamation, and hyperresponsiveness are characteristics of the airway inflammation underlying bronchial asthma. The contribution of intercellular adhesion molecule-1 (ICAM-1) to eosinophil migration and airway responsiveness was studied. ICAM-1 partially mediated eosinophil adhesion to to endothelium in vitro and was upregulated on inflamed bronchial endothelium in vivo. ICAM-1 expression was also upregulated on inflamed airway epithelium in vitro and in vivo. In a primate model of asthma, a monoclonal antibody to ICAM-1 attenuated airway eosinophilia and hyperresponsiveness. Thus, antagonism of ICAM-1 may provide a therapeutic approach to reducing airway inflammation, hyperresponsiveness, and asthma symptoms.

https://science.sciencemag.org/content/sci/247/4941/456.full.pdf

Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma

Inhalation of histamine diphosphate aerosol (16 per cent, 10 breaths) produced a 218 ± 546 per cent (mean ± SE) increase in airway resistance in 16 normal subjects with colds compared with a 305 ± 55 per cent increase in 11 healthy control subjects (P < 001) There was no significant difference in mean baseline airway resistance between the two groups Inhalation of saline produced no significant change in airway resistance in either group Isoproterenol hydrochloride (05 per cent, 1 breath) or atropine sulfate aerosol (02 per cent, 20 breaths) each reversed and prevented the increase in airway resistance by histamine, indicating that the bronchoconstriction was caused by smooth muscle contraction and that post-ganglionic, cholinergic pathways were involved in the mechanism In 6 subjects with colds, citric acid aerosol (10 per cent, 5 breaths) caused bronchoconstriction that lasted up to 30 sec after inhalation, a significantly greater effect than that observed in control subjects or in the same s

Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection.

Fourteen healthy male subjects with hemagglutination-inhibition antibody titers of 1:8 or less to homologous influenza A virus were studied. Six subjects received live, attenuated influenza virus by nasal drops and by aerosol. Although infection occurred in these six subjects, with the development of 4-fold or greater increases in hem agglutination-inhibit ion antibody titers, they remained asymptomatic. Eight subjects received placebo via the same route, and did not develop symptoms and showed no increase in antibody titer. Prior to administration of virus or placebo, histamine diphosphate aerosol increased airway resistance only slightly, and there was no difference between the virus and placebo groups. Two days after inoculation, bronchomotor responses in the placebo group were unchanged (p > 0.05), but in the virus-infected group, bronchomotor responses were significantly greater than in the preinfected state (p < 0.01). Isoproterenol hydro-chloride reversed and prevented the increase in airway resist...

L. Jacobs

Papers

Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection.

Bronchial Hyperresponsiveness in Normal Subjects during Attenuated Influenza Virus Infection