MethaCholine Bronchoprovocation Study (MeCIS)

Phase 4

Completed

Brief Summary: The purpose of this research is to evaluate the methacholine challenge test as an accurate indicator of asthma in patients receiving treatment for asthma. Phase 1 on the study compares methacholine challenge test results from asthma patients to those from people who do not have asthma. In phase 2, test results for people with asthma on low dose inhaled corticosteroid will be compared to results on high dose inhaled corticosteroids. Both males and females with stable asthma (asthma participants) and without asthma (controls) enrolled. Participants will be between 12 and 69 years of age.

Detailed Description: The study consists of two phases. The first phase is a cross-sectional, case-control study measuring the sensitivity and specificity of methacholine challenge testing for differentiating asthmatic participants from non-asthmatic controls. The second phase is a cross-over, randomized, double-masked trial designed to evaluate the impact of high dose versus low dose inhaled corticosteroids (ICS) on bronchial hyperreactivity (BHR) in asthmatics.

Recruitment & Eligibility

Inclusion Criteria

Males or females greater than or equal to 12 and less than 70 years of age
Physician-diagnosed and investigator-confirmed stable asthma (excluding exercise induced asthma)
Current treatment for asthma by a healthcare provider within the preceding twelve months: current asthma treatment defined as regular use of asthma medications. Asthma medications include short and long acting adrenergic bronchodilators, bronchodilator combinations, inhaled anticholinergics, inhaled corticosteroids, cromolyn sodium and nedocromil, leukotriene modifiers and methylxanthines
Stable asthma defined by no asthma exacerbation (emergency room visit, hospitalization, course of increased systemic steroids, or urgent health care visit for asthma) during the prior four weeks
Forced expiratory volume at one second (FEV1) >70% predicted pre-bronchodilator
Ability to provide screening and baseline information
Ability and willingness to provide informed consent
For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study

Exclusion Criteria

Chronic oral steroid therapy (daily)
Oral corticosteroid use within past 4 weeks
Respiratory tract infection within past 4 weeks
Chronic diseases (other than asthma) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, or nervous system, or immunodeficiency
Known allergy to methacholine (for example, a previous bad reaction to methacholine) or to any other parasympathomimetic agents
Current use of beta adrenergic blocking agent (a heart medicine) or a cholinesterase inhibitor (medicine used to treat myasthenia gravis or Alzheimer's disease).
History of epilepsy, cardiovascular disease with bradycardia (slow heart beat), vagotonia (increased activity of the vagus nerve causing slow heart rate or low blood pressure), peptic ulcer disease, thyroid disease, or urinary tract obstruction
History of cigarette smoking within the past 5 years or >10 pack years total
Use of investigative drugs or intervention trials in the 30 days prior to enrollment or during the duration of the study
Any condition or compliance issue which in the opinion of the investigator might interfere with participation

Nonasthmatic control criteria:

Inclusion Criteria:

Males or females greater than or equal to 12 and less than 70 years of age
Individuals who are in good overall health
Age (within ten years for above 25 years of age and +/- five years for 12-25 years of age) and sex matched to the asthmatic group

Exclusion Criteria:

A subject will be excluded if there is a history within the previous 5 years of:
- clinically diagnosed allergy (allergic rhinitis, hay fever or atopic dermatitis),
- asthma (beyond 6 years of age),
- chronic nasal or sinus disease, or
- other chronic lung diseases
Respiratory tract infection within past 4 weeks
History of cigarette smoking within the past 5 years or >10 pack years total
Known allergy to methacholine (for example, a previous bad reaction to methacholine) or to any other parasympathomimetic agents
Current use of beta adrenergic blocking agent (a heart medicine) or a cholinesterase inhibitor (medicine used to treat myasthenia gravis or Alzheimer's disease).
History of epilepsy, cardiovascular disease with bradycardia (slow heart beat), vagotonia (increased activity of the vagus nerve causing slow heart rate or low blood pressure), peptic ulcer disease, thyroid disease, or urinary tract obstruction

Arm && Interventions

Group	Intervention	Description
Low dose fluticasone for phase 2	fluticasone	For people with asthma, fluticasone at 250 mcg per day; phase 2 of study
High dose fluticasone for phase 2	fluticasone	For people with asthma, fluticasone at 1000 mcg per day; phase 2 of study

Primary Outcome Measures

Name	Time	Method
Methacholine Challenge Test Result for Phase 2	weeks 0, 4	Presence and degree of airway hyperresponsiveness assessed by methacholine challenge test post-diluent baseline (PC20) after medication holds; PC20 is the methacholine dose at which the amount of air expired in the first second during a forced expiratory maneuver is reduced by 20%; value represents change in baseline to 4 weeks

Secondary Outcome Measures

Name	Time	Method
Predictive Value of Methacholine Challenge Test for Phase 1	one time	Predictive value of methacholine challenge test in phase 1 for asthmatics and nonasthmatic controls

Locations (13): Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States
University of Miami/Univestiy of South Florida
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Miami, Florida, United States
Northwestern University Memorial Hospital
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Chicago, Illinois, United States
The Nemours Children's Clinic
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Jacksonville, Florida, United States
Indiana University
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Indianapolis, Indiana, United States
University of California at San Diego
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San Diego, California, United States
Louisianna State University
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New Orleans, Louisiana, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Vermont Lung Center at the University of Vermont
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Burlington, Vermont, United States
New York Consortium/Columbia University
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New York, New York, United States
University of Missouri-Kansas City
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Kansas City, Missouri, United States
Long Island Jewish Medical Center
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New Hyde Park, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States