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Trial registered on ANZCTR


Registration number
ACTRN12615000079549
Ethics application status
Approved
Date submitted
9/01/2015
Date registered
30/01/2015
Date last updated
30/01/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Early detection of lung disease in smokers with normal spirometry
Scientific title
Multiple breath nitrogen washout (MBNW) and impulse oscillometry system (IOS) to detect small airway disease in smokers with normal spirometry
Secondary ID [1] 285935 0
Nil
Universal Trial Number (UTN)
U1111-1165-8083
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 293863 0
Condition category
Condition code
Respiratory 294166 294166 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There will be one (1) visit for this study which will either take place at the Woolcock Institute of Medical Research or at the Respiratory Investigation Unit at Royal North Shore Hospital. The visit will last around 90 minutes. All tests that we will administer are used routinely for lung function testing in hospital lung function laboratories in Australia and internationally.

We will perform an allergy test called a skin prick test. A small droplet of allergen will be placed on subject's forearm and the skin will be pricked lightly through the droplet. If subject is allergic to any of the allergens you will develop a small itchy lump, like a mosquito bite.

Subject's lung size will be measured in a body plethysmograph. This requires sitting in a clear Perspex booth during which subject will be asked to breathe on a mouth piece.Subject will be asked to breathe at different speeds and to take in a slow deep breath and then breathe out slowly and push all the air out of your lungs. The whole test will take approximately 15 minutes.


Two types of simple breathing tests will be conducted to measure how efficient subject's lungs are at moving air in and out. For the first test, known as spirometry, subject will be asked to take a deep breath and blow as hard and fast as you can for as long as you can into the mouthpiece. This manoeuvre will be repeated three times, and will take five minutes. For the second test, subject will be asked to breathe quietly on a mouthpiece for one minute while wearing a nose clip. Subject will feel a slight “flutter” in the air that he will breathe during this test, but it will not cause any discomfort.

A washout test will tell us how evenly air is distributed throughout the lungs. Subject will breathe into a mouthpiece, keeping the size of your breaths within a set range. During the test you will first breathe normal room air and then 100% oxygen for approximately 20 breaths. Each test is performed 3 times and it takes about 20-25 minutes to complete all three tests.
All the measurements will be made before and 20 minutes after inhalation of 200microgram of salbutamol (2 puffs) and 80 microgram of ipratropium bromide (4 puffs) via metered dose inhaler and large volume spacer in smokers with normal spirometry.
Intervention code [1] 290911 0
Early detection / Screening
Comparator / control treatment
Spirometry, body plethysmography, single-breath diffusing capacity for carbon monoxide (DLCO), MBNW and IOS measurements will be made before and 20 minutes after inhalation of 200microgram of salbutamol and 80 microgram of ipratropium bromide via metered dose inhaler and large volume spacer in never smokers with normal spirometry.
Control group
Active

Outcomes
Primary outcome [1] 293957 0
Calculate the sensitivity and specificity of impulse oscillometry technique (IOS) and multiple breath nitrogen washout technique (MBNW) in detection of smoking induced peripheral airway altercation in smokers with normal spirometry
The reference values for IOS will be those of Newbury et al and values for spirometry will be those of Quanjer et al. We will use receiver operator curve (ROC) analysis to determine the specificity and sensitivity for IOS parameters to detect small airways disease, defined as abnormal Sacin or Scond. We will also compare the proportions of subjects who have abnormal values for IOS and MBNW using chi-square analyses. Relationships with smoking history will be examined using correlation analyses.
non smokers will not be included in this analaysis
Timepoint [1] 293957 0
The outcome will be measured after all the data has been collected for smokers with normal spirometry.
Secondary outcome [1] 312231 0
To determine whether abnormalities in Sacin and Scond (measured using MBNW) and resistance and reactance (measured using IOS) in smokers with normal spirometry were normalised by inhalation of short acting beta agonist and anti-cholinergic.
Timepoint [1] 312231 0
The response will be measured after acute administration of bronchodilator (after 20 minutes of administration).
The improvement in Sacin and Scond and resistance and reactance in smokers will be compared against non smokers. Bronchodilator response and differences between groups were examined using t-tests, Mann–Whitney-U tests or Kruskal-Wallis and post hoc Dunn-Bonferroni tests as appropriate. Correlations were examined using Spearman correlation coefficients.

Eligibility
Key inclusion criteria
Smokers with greater than equal to 10 Pack years of smoking history and Normal spirometry defined as FEV1> 80% predicted and FEV1/FVC greater than 0.70
Non smokers with Normal spirometry defined as FEV1> 80% predicted and FEV1/FVC greater than 0.70
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any history of respiratory disease or cardiovascular disease.
Women who are pregnant
People who are unable to understand the patient information statement
Same criteria for never smokers will be included

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3307 0
Royal North Shore Hospital - St Leonards

Funding & Sponsors
Funding source category [1] 290519 0
Commercial sector/Industry
Name [1] 290519 0
GlaxoSmithKline
Address [1] 290519 0
Level 4, 436 Johnston Street, Abbotsford, Victoria, 3067, Australia
Country [1] 290519 0
Australia
Primary sponsor type
Individual
Name
Kanika Jetmalani
Address
Woolcock Institute of Medical Research
431 Glebe point Road, Glebe, NSW, 2037
Country
Australia
Secondary sponsor category [1] 289213 0
Individual
Name [1] 289213 0
A/Prof. Gregory King
Address [1] 289213 0
Woolcock Institute of Medical Research
431 Glebe point Road, Glebe, NSW, 2037
Department of Respiratory Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards, NSW, 2065
Country [1] 289213 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292169 0
Northern Sydney Central Coast Area Health Service Human Research Ethics Committee
Ethics committee address [1] 292169 0
Research Office
Royal North Shore Hospital
St. Leonards, NSW, 2065
Ethics committee country [1] 292169 0
Australia
Date submitted for ethics approval [1] 292169 0
Approval date [1] 292169 0
28/11/2011
Ethics approval number [1] 292169 0

Summary
Brief summary
In chronic obstructive pulmonary disease (COPD), commonly associated with long term smoking, the earliest abnormality occurs in the very small airways. However, these changes to the small airways are unable to be detected by common lung function tests used in clinical practice and therefore early detection of COPD at present is impossible. In our laboratory we have two easy-to-perform lung function tests that are sensitive to abnormalities in the small airways and we want to determine whether these tests are able to detect abnormalities when common lung function tests remain normal and if they can be treated with administration of bronchodilators. If either of these tests are sensitive to small airway abnormalities it will mean that they have the potential to be used for the early detection of COPD in smokers.

We hypothesise that IOS parameters will be sensitive to alterations in small airway function, as defined by
abnormal ventilation heterogeneity measured by MBNW, in smokers with normal spirometry. Also, these abnormalities may be partially of completely reversed with bronchodilators.
Trial website
Trial related presentations / publications
1. K Jetmalani, A Bertolin, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2014), Can impulse oscillometry detect peripheral airway abnormalities measured using multiple breath nitrogen washout (MBNW) in asymptomatic smokers? Am J Respir Crit Care Med. 189 (meeting abstracts), P: A3547.
2. K Jetmalani, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2014), Is increased bronchomotor tone an important driving factor in developing acinar airway abnormalities in smokers with normal spirometry? Respirology. 19 suppl. 2. P: 2-6.
3. K Jetmalani, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2013), Small airway function in smokers with normal spirometry improves with bronchodilator. Am J Respir Crit Care Med. 187 (meeting abstracts), P: A1934.
4. K Jetmalani, D Chapman, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2013), Role of bronchomotor tone in developing acinar airway abnormalities in smokers with normal spirometry. Proceedings of XIIIth Annual Bosch Young Investigator Symposium. P: 21
5. K Jetmalani, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2013), Abnormal airway function in smokers with normal spirometry. Respirology. 18 suppl. 2. P: 4.
6. K Jetmalani, CS Farah, NJ Brown, N Berend, CM Salome, GG King (2013), Small airway function in smokers with normal spirometry improves with bronchodilator. Respirology. 18 suppl. 2. P: 20.


Public notes

Contacts
Principal investigator
Name 53894 0
Miss Kanika Jetmalani
Address 53894 0
Woolcock Institute of Medical Research
431 Glebe Point Road, Glebe
NSW 2037
Country 53894 0
Australia
Phone 53894 0
+61291140147
Fax 53894 0
Email 53894 0
kanika.jetmalani@sydney.edu.au
Contact person for public queries
Name 53895 0
Miss Kanika Jetmalani
Address 53895 0
Woolcock Institute of Medical Research
431 Glebe point Road, Glebe, NSW, 2037
Country 53895 0
Australia
Phone 53895 0
+61291140147
Fax 53895 0
Email 53895 0
kanika.jetmalani@sydney.edu.au
Contact person for scientific queries
Name 53896 0
Miss Kanika Jetmalani
Address 53896 0
Woolcock Institute of Medical Research
431 Glebe point Road, Glebe, NSW, 2037
Country 53896 0
Australia
Phone 53896 0
+61291140147
Fax 53896 0
Email 53896 0
kanika.jetmalani@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary