Clinical trial NCT03320382: Multiple Breath Washout, a Clinimetric Dataset
Official title: Multiple Breath Washout in Paediatric Chronic Airways Disease: Building a Clinimetrics Dataset
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cystic Fibrosis
Primary Ciliary Dyskinesia
Bronchiectasis
Asthma
Bronchitis
Sleep Disorder
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2017-10-25
Enrollment: 530
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged two and upwards with chronic airways disease including CF, PCD, Asthma and Bronchiectasis, Persistent bacterial bronchitis and sleep disordered breathing and obesity as well as aged matched healthy control patients will be approached to take part in the study.

Healthy volunteers will only complete MBW and Spirometry for comparison with respiratory disease patients.

Brief summary: Monitoring patients with chronic, inflammatory airways disease particularly in the early stages is hampered by the relative insensitivity of current outcome measures to detect subtle changes. Multiple breath washout is a potential sensitive test that is a useful readout of disease at these early stages but it lacks standardisation and knowledge of variability with reference to standard lung function measures. This is a Cross sectional and longitudinal observation study. The hypothesis is that multiple breath washout-derived indices will provide a robust signal of gas mixing inhomogeneity, correlating with conventional measures of airway disease severity. Multiple breath washout performed on different devices will generate indices which correlate but differ in value.

Detailed description: Lung Clearance Index (LCI) has been shown to be more sensitive and perhaps more applicable in early stages of lung disease when compared to currently utilised physiological outcome measures, and yet it is not approved by regulatory agencies as a recognised surrogate outcome measure. This may highlight some of the lack of understanding within MBW; what is the best equipment to use, what is the minimal value of change to show an improvement in LCI, what is LCI's correlation with clinical outcome measures and what does the progression of LCI tell us about lung disease. These questions will be addressed with a view to contributing a body of data to guide decisions around its utility in both interventional drug trials and for monitoring in a clinical setting.

The aim of this study is to assess the suitability of LCI as a clinical outcome measure for both clinical trials and clinical monitoring of patients with inflammatory respiratory disease across the disease spectrum. Different testing modalities will be compared as well as assess the repeatability and validity of LCI for its determination as an outcome measure. Long-term follow up will allow an assessment of the relationship between LCI and future outcomes such as rate of decline in lung function and frequency of exacerbations, both recognised as relevant by regulatory agencies.

Eligibility criteria: Inclusion criteria

* For patients with the following respiratory disease, diagnosis confirmed by:
* CF: diagnosed by standard criteria
* PCD: diagnosed by ciliary beat frequency measurement, ciliary beat pattern analysis or electron microscopy of ciliary ultrastructure, or genetics
* Non-CF bronchiectasis: CT diagnosis of bronchiectasis and not fulfilling diagnostic criteria for CF or PCD
* Asthma: as diagnosed by standard diagnostic criteria of British Thoracic Society/Scottish Intercollegiate Guideline Network (BTS/SIGN) guidelines.
* Persistent bacterial bronchitis defined as a wet cough present for \>1 month, usually with bronchoscopic evidence of chronic infection, that resolves with appropriate antibiotic therapy
* Sleep Disordered Breathing.
* For healthy volunteers, these will be colleagues and staff contacts (including children) at a participating centre i.e. Royal Brompton Hospital, or will be siblings of patients.
* Written informed consent (assent from children of appropriate age) obtained.

Exclusion criteria

* Positive culture (within the last year of / receiving treatment for Mycobaterium tuberculosis or abscessus (due to cross-infection concerns).
* Pregnant or breastfeeding.
* Inability to understand or cooperate with the test(s).
* Inability to give informed consent, or withdrawal of informed consent.

Primary outcomes:
measure: Lung Clearance Index
timeFrame: Each testing session may take up to 90 minutes but most likely it will be under an hour. The MBW test will be completed at each visit and the LCI and other MBW results are obtained from data analysis post completion.
Secondary outcomes:
measure: Spirometry
timeFrame: Spirometry will be completed at each visit (unless already taken at a clinical visit). Maximum 10 visits over 3 years
measure: Disease specific Quality of life questionnaire
timeFrame: The quality of life questionnaire will be completed at each visit and compared to the primary outcome at each visit. Maximum 10 visits over 3 years
measure: Review of clinically indicated tests
timeFrame: Post each visit review of clinically indicated tests will take place and compared to the primary outcome. Maximum 10 visits over 3 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Imperial College London
name: Jane C Davies, Professor
role: PRINCIPAL_INVESTIGATOR
References: