The Correlation Between Airway Inflammation and Loss of Deep Inhalation Bronchoprotection in Asthmatics

The loss of deep inhalation bronchoprotection in asthmatic individuals has been shown to be related to the degree of airway hyperresponsiveness, a hallmark of asthma. In several studies, asthmatic individuals with mild airway hyperresponsiveness (AHR) (methacholine PC20 > 2 mg/mL) had a difference in methacholine PC20 with and without deep inhalations that averaged 1.8 doubling methacholine concentrations (p=0.0003). Conversely, asthmatic individuals with moderate to severe AHR (methacholine PC20 ≤ 2 mg/mL) had a non-significant difference in methacholine PC20 with and without deep inhalations (p=0.09). This loss of deep inhalation bronchoprotection is also now believed to play an important role in the pathogenesis of asthma. Airway inflammation is another of the key features of asthma and information on airway inflammation is increasingly being used in the diagnosis and treatment of asthma. The level of airway inflammation (as measured by fraction of exhaled nitric oxide and sputum eosinophilia) has also been shown to be correlated to the level of airway hyperresponsiveness (as measured by methacholine PC20). In addition, glucocorticoids have been shown to decrease airway hyperresponsiveness, further suggesting that these two phenomena, airway inflammation and airway hyperresponsiveness, are related. We therefore suggest that the degree of airway inflammation is related to the loss of deep inhalation bronchoprotection and expect there to be a negative correlation between the degree of deep inhalation bronchoprotection and airway inflammation.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: deep inhalation

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of asthma

Exclusion Criteria:

• other lung disease(s)
• smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard; Methacholine challenges are performed using the standardized two minute tidal breathing method	Other: deep inhalation; deep inhalation is comprised of an inhalation manoeuver from FRC to TLC
Active Comparator: Modified; Five deep inhalation maneouvers are incorporated into the standardized methacholine challenge	Other: deep inhalation; deep inhalation is comprised of an inhalation manoeuver from FRC to TLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
fraction of exhaled nitric oxide, sputum eosinophils and methacholine PC20	freaction of exhaled nitric oxide data collected prior to methacholine challenges; sputum collected after the first methacholine challenge

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Donald Cockcroft, MD, FRCP(C), Department of Medicine, Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: November 27, 2006
• First Submitted That Met QC Criteria: November 27, 2006
• First Posted (Estimate): November 29, 2006

Study Record Updates

• Last Update Posted (Estimate): January 23, 2008
• Last Update Submitted That Met QC Criteria: January 18, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: BIO-REB 06-92