The Natural History of Small Airways Physiology in Diseased and Healthy States

Impulse Oscillometry and Airway Inflammation in Asthma and Chronic Obstructive Pulmonary Disease and Airways Physiology in Other Lung Conditions and Healthy Lungs

Spirometry is a useful clinical tool for the assessment and monitoring of lung disease, however, it does not provide information on peripheral airways resistance. On the contrary, impulse oscillometry (IOS) may provide information not only on airway resistance (Rrs) but also on the elastic properties of the lung (Xrs). In addition, multiple breath nitrogen washout (MBNW) utilizes the exhalation of nitrogen gas from the airways to determine changes in lung ventilation and derive small airways indices (that tells us about small airways calibre). This method, like IOS, allows a precise assessment of small airways function.

Even though patients with asthma may show some reduction of the caliber of the small airways these changes are more a feature of patients with COPD. The study team hypothesize that IOS and MBNW measurements may detect these differences and provide different resistance profiles for asthma and COPD. Furthermore, the study team would like to investigate the relationship between airway inflammation and small airway disease by measuring exhaled nitric oxide (NO) at multiple exhalation flow rates. This technique allows the partitioning of NO produced in the central airways from that generated more peripherally in the lung, providing valuable information on the activity of inflammation in different parts of the respiratory system. The study team hope that the combined use of IOS, MBNW and NO will identify a possible correlation between inflammation and small airway dysfunction.

Study Overview

• Status: Completed
• Conditions: Asthma; Cystic Fibrosis; Interstitial Lung Disease; COPD; Patients Requiring Lung Transplant

Detailed Description

Background

The main objective of this study is to measure the damage of the small airways in lung disease exploring the "silent zone" with methods that have not been used before together in the same patients. Furthermore, because this is a 4 year longitudinal study, the study team will investigate the time related changes of small airway function in lung disease and normal healthy subjects.

The study will also investigate the relationship between small airway resistance and inflammation.

• Study Type: Observational
• Enrollment (Actual): 126

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6LY
    • Airway Disease Section, National Heart and Lung Institute, Imperial College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients will be recruited from outpatient clinics

Description

Inclusion Criteria:

• male or female, aged between 18-85 years;
• volunteers who are able to give written informed consent Patients meeting the diagnostic criteria for asthma, COPD, ILD, CF, chronic cough.

Exclusion Criteria:

• upper respiratory tract infection within the previous 28 days
• any history or evidence of renal, cardiovascular, gastrointestinal or hepatic disease
• any history and evidence of neuropsychiatric disease
• treatment with antibiotics within 4 weeks prior to the study
• alcohol, drug abuse or any other condition associated with poor compliance
• breast feeding
• pregnancy
• are unable to provide written informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
3; Mild-moderate asthma. Within the asthma group, there were two sub-groups; mild-moderate asthma and severe asthma distinguished using the Global Initiative for Asthma (GINA) guidelines (GINA, 2009).
4; Severe Asthma Within the asthma group, there were two sub-groups; mild-moderate asthma and severe asthma distinguished using the Global Initiative for Asthma (GINA) guidelines (GINA, 2009).
1; Normal subjects Normal subjects were a group made up of healthy subjects, with normal lung function, non-smokers at the time of the screening.
2; Healthy smokers Healthy smokers were comprised of people who were current smokers and had normal lung function at the time of screening.
5; COPD (Gold stage I - III) The COPD group included stage I to III patients, classified according to severity of airflow limitation (post bronchodilator FEV1), from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (GOLD, 2011).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1	Forced expiratory volume in one second	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calv	Nitric oxide arising from the alveolar compartment.	120 minutes
AX	Reactance area for whole-breath	120 minutes
R5 EX	Resistance measured at 5 hertz during expiration	120 minutes
J'aw	Bronchial nitric oxide flux	120 minutes
Sacin	Ventilation heterogeneity within the acinar airways	120 minutes
Scond	Ventilation heterogeneity within the conducting airways	120 minutes

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Study Director: Paolo Paredi, MD, PhD, Airway Disease Section, National Heart and Lung Institute, Imperial College, London; Principal Investigator: Omar A Usmani, MD, PhD, Airway Disease Section, National Heart and Lung Institute, Imperial College, London; Study Chair: Peter J Barnes, Prof, Airway Disease Section, National Heart and Lung Institute, Imperial College, London; Study Chair: Neil Pride, Prof, Airway Disease Section, National Heart and Lung Institute, Imperial College, London; Study Chair: Michael Goldman, Prof, Airway Disease Section, National Heart and Lung Institute, Imperial College, London

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2010
• Primary Completion (ACTUAL): July 10, 2013
• Study Completion (ACTUAL): July 10, 2013

Study Registration Dates

• First Submitted: May 12, 2008
• First Submitted That Met QC Criteria: May 13, 2008
• First Posted (ESTIMATE): May 14, 2008

Study Record Updates

• Last Update Posted (ACTUAL): December 20, 2021
• Last Update Submitted That Met QC Criteria: November 3, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: lung function; inflammation; resistance; respiratory function; reactance
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Pancreatic Diseases; Lung Diseases; Asthma; Cystic Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: 08/H0709/2