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

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00677560
• Collaborator: (none)
• Enrollment: 126
• Location: 1
• Actual Duration (Months): 36.6
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma; COPD; Interstitial Lung Disease; Cystic Fibrosis; 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 Design

• Study Type: Observational
• Actual Enrollment: 126 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Impulse Oscillometry and Airway Inflammation in Asthma and Chronic Obstructive Pulmonary Disease and Airways Physiology in Other Lung Conditions and Healthy Lungs
• Actual Study Start Date: Jun 22, 2010
• Actual Primary Completion Date: Jul 10, 2013
• Actual Study Completion Date: Jul 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

1. FEV1 [120 minutes]

   Forced expiratory volume in one second

Secondary Outcome Measures

1. Calv [120 minutes]

   Nitric oxide arising from the alveolar compartment.

2. AX [120 minutes]

   Reactance area for whole-breath

3. R5 EX [120 minutes]

   Resistance measured at 5 hertz during expiration

4. J'aw [120 minutes]

   Bronchial nitric oxide flux

5. Sacin [120 minutes]

   Ventilation heterogeneity within the acinar airways

6. Scond [120 minutes]

   Ventilation heterogeneity within the conducting airways

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Airway Disease Section, National Heart and Lung Institute, Imperial College	London		United Kingdom	SW3 6LY

Sponsors and Collaborators

• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00677560
• Other Study ID Numbers: 08/H0709/2
• First Posted: May 14, 2008
• Last Update Posted: Dec 20, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Imperial College London: resistance; reactance; inflammation; lung function; respiratory function
• Additional relevant MeSH terms: Cystic Fibrosis; Asthma; Lung Diseases; Lung Diseases, Interstitial

Study Results

Participant Flow

Recruitment Details	This was a single centre cross-sectional and longitudinal study involving asthmatic and chronic obstructive pulmonary disease (COPD) patients and healthy volunteers (including smokers). Subjects were between the ages of 18-85 years old, were given a patient information sheet and provided their written informed consent. Subjects were interviewed at visit 1 and a medical history was documented.

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I - III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease.	Healthy smokers had no history of respiratory disease, and were all current smokers	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Period Title: Overall Study
STARTED	20	23	29	20	34
COMPLETED	5	13	6	3	21
NOT COMPLETED	15	10	23	17	13

Baseline Characteristics

Arm/Group Title	Normal Subjects	Healthy Smokers	Mild-moderate Asthma	Severe Asthma	COPD (Gold Stage I - III)	Total
Arm/Group Description	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).	Total of all reporting groups
Overall Participants	29	20	20	23	34	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (15)	55 (10)	41 (15)	50 (14)	66 (7)	54 (15)
Sex: Female, Male (Count of Participants)
Female	14 48.3%	9 45%	13 65%	6 26.1%	16 47.1%	58 46%
Male	15 51.7%	11 55%	7 35%	17 73.9%	18 52.9%	68 54%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	168.2 (10.7)	167.2 (11.3)	174.3 (10.1)	168.7 (8.5)	164.4 (8.5)	168.1 (10.1)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	73.05 (17.99)	66.95 (15.55)	76.30 (17.19)	76.00 (13.18)	69.75 (14.04)	72.2 (15.8)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.63 (4.80)	23.90 (4.82)	24.90 (4.04)	26.89 (5.64)	25.76 (4.57)	25.5 (4.8)
Smoking status (participants) [Number]
Current smokers	0 0%	20 100%	0 0%	0 0%	10 29.4%	30 23.8%
Ex-smokers	0 0%	0 0%	3 15%	1 4.3%	22 64.7%	26 20.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I-III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	20	23	29	20	34
Mean (Standard Deviation) [L]	3.03 (0.80)	2.32 (0.88)	3.18 (0.79)	2.76 (0.73)	1.67 (0.44)

2. Secondary Outcome

Title	Calv
Description	Nitric oxide arising from the alveolar compartment.
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I - III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	20	23	29	20	34
Mean (Standard Error) [ppb]	4.3 (3.6)	3.8 (3.2)	2.9 (1.7)	4.6 (2.9)	3.7 (2.6)

3. Secondary Outcome

Title	AX
Description	Reactance area for whole-breath
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I - III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease.	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	20	23	29	20	34
Mean (Standard Deviation) [kPa/L]	1.03 (1.05)	1.88 (2.20)	0.55 (0.57)	0.82 (0.93)	2.48 (2.12)

4. Secondary Outcome

Title	R5 EX
Description	Resistance measured at 5 hertz during expiration
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I - III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	1357
Measure Participants	20	23	29	20	34
Mean (Standard Deviation) [kPa/L/s]	0.50 (0.17)	0.60 (0.21)	0.45 (0.16)	0.50 (0.25)	0.66 (0.24)

5. Secondary Outcome

Title	J'aw
Description	Bronchial nitric oxide flux
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I - III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	20	23	29	20	34
Mean (Standard Deviation) [nl/s]	138.5 (85)	77.2 (62.4)	76.2 (46.1)	35.4 (21.2)	60.7 (47.6)

6. Secondary Outcome

Title	Sacin
Description	Ventilation heterogeneity within the acinar airways
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mild-moderate Asthma	Severe Asthma	Normal Subjects	Healthy Smokers	COPD (Gold Stage I-III)
Arm/Group Description	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	20	23	29	20	34
Mean (Standard Deviation) [/L]	0.122 (0.094)	0.214 (0.194)	0.089 (0.051)	0.150 (0.084)	0.346 (0.139)

7. Secondary Outcome

Title	Scond
Description	Ventilation heterogeneity within the conducting airways
Time Frame	120 minutes

Outcome Measure Data

Analysis Population Description

Not all subjects have results for this parameter which is why the total number of results will not equal the number of participants recruited.

Arm/Group Title	Normal Subjects	Healthy Smokers	Mild-moderate Asthma	Severe Asthma	COPD (Gold Stage I - III)
Arm/Group Description	This group consisted of 29 never-smokers with no history of respiratory disease	The healthy smoking group consisted of 20 current smokers with no history of respiratory disease	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009).	COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011).
Measure Participants	27	20	16	22	32
Mean (Standard Deviation) [/L]	0.041 (0.016)	0.068 (0.027)	0.045 (0.015)	0.057 (0.026)	0.057 (0.020)

Adverse Events

Arm/Group Title	Mild-moderate Asthma		Sever Asthma		Normal Subjects		Healthy Smokers		COPD (Gold Stage I - III)
Arm/Group Description	Mild-moderate asthma recruited at baseline		Sever Asthma recruited at baseline		Normal subjects at baseline		Healthy smokers at baseline		COPD (Gold stage I - III) baseline
All Cause Mortality
	Mild-moderate Asthma		Sever Asthma		Normal Subjects		Healthy Smokers		COPD (Gold Stage I - III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mild-moderate Asthma		Sever Asthma		Normal Subjects		Healthy Smokers		COPD (Gold Stage I - III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)		0/29 (0%)		0/20 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Mild-moderate Asthma		Sever Asthma		Normal Subjects		Healthy Smokers		COPD (Gold Stage I - III)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)		0/29 (0%)		0/20 (0%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.