Title: Comparison of Lower Airway Sampling Strategies In Children with PBB (CLASSIC PBB)
Funder: Department of Health and Social Care

Abstract: Research question Is a cough swab or an induced sputum a useful alternative to bronchoalveolar lavage samples obtained during flexible bronchoscopy (FB-BAL) as a method of identifying lower airway pathogens in children with protracted bacterial bronchitis (PBB)? Background PBB is the commonest cause of chronic wet cough in young children from developed countries. It is caused by chronic bacterial infection of the conducting airways. PBB can be treated with antibiotics but relapses are common and recurrent episodes are associated with subsequent bronchiectasis. Identification of the causative pathogen allows antibiotic choice to be targeted, increasing treatment success and reducing antibiotic resistance. However, affected children rarely expectorate sputum and the only strategy commonly used to sample the lower airway is FB-BAL. This is reserved for those with treatment resistant or recurrent PBB as it is invasive and requires a general anaesthetic. Current practice varies as to whether FB-BAL samples are obtained from one, two or six lobes. Cough swabs and induced sputum samples are non-invasive methods of sampling the lower airway widely used in other respiratory conditions and well toelrated. If either were shown to be a useful alternative to FB-BAL in children with PBB, it would reduce burden for families, reduce NHS costs and enable lower airway sampling in more children. Aims and Objectives Aim To investigate if two non-invasive strategies for sampling the lower airway are useful alternatives to FB-BAL. Objectives To compare pathogen yield in children with PBB between an induced sputum sample and FB-BAL samples To compare pathogen yield in children with PBB between a cough swab and FB-BAL samples.. Methods Children aged 1-10 years with PBB in whom FB-BAL is clinically indicated will be eligible for the study. Children will be identified in respiratory outpatient clinics from five UK centres. The study will be discussed with the families of eligible children and relevant information provided. On the day of the child s FB-BAL, those who agree to take part will attend the hospital one hour earlier than would normally be required. Following informed consent, a paediatric physiotherapist will obtain a cough swab and an induced sputum sample using existing, standardised methodologies prior to the FB-BAL. The FB-BAL is clinically indicated and not part of the research protocol. It will, however, be performed using a standard methodology in which all six lobes (including lingula) are sampled. All samples will be individually cultured and reported semi-quantitative. The primary outcomes are the discordance in pathogen yield between 1) induced sputum and FB-BAL and 2) cough swab and FB-BAL. Timelines for delivery The 24 month project consists of three months set-up, 17 months recruitment and delivery, two months data analysis and two months write-up and dissemination. Anticipated Impact and Dissemination The results of this study will be submitted for presentation at an international meeting and publication in a high-impact, peer-reviewed journal. If either of the non-invasive techniques are shown to be useful alternatives to FB-BAL there will be a significant impact on clinical care for a large number of children.

Lay abstract: What is Protracted bacterial bronchitis (PBB)? PBB is a type of chest infection in young children. It causes a persistent cough which affects school performance, limits activity and disrupts sleep. It is treated with antibiotics but prolonged and / or multiple courses are often required. Recurrent episodes can result in permanent lung damage. Knowing which bug is causing the infection, guides antibiotic choice and reduces the risk of antibiotic resistance but this requires a lower airway sample. What is the problem? Lower airway samples are difficult to obtain in PBB as affected children rarely cough up sputum. It is done by taking a washing (bronchoalveolar lavage - BAL) during a camera test of the lungs (flexible bronchoscopy - FB). This is invasive and requires a general anaesthetic. Although safe, it is only available at specialist centres and causes significant disruption to families. FB-BAL is therefore only used in PBB if the cough does not improve with treatment or frequently relapses. What do we want to find out? We want to find out if two non-invasive methods of obtaining lower airway samples (cough swab and induced sputum) are useful alternatives to FB-BAL. Both are commonly used and well tolerated in children with other lung conditions. What are we going to do? Children with PBB at five children s hospitals referred by their doctor for FB-BAL will be eligible. Informed consent will be obtained. When the child attends hospital for FB-BAL, a cough swab and induced sputum will be obtained by a physiotherapist prior to the procedure. No additional visits are required. A cough swab is taken by coughing on a swab (size of a cotton bud) held in the mouth. An induced sputum is obtained by breathing in salt solution before chest physiotherapy (patting or breathing exercises). Bugs identified from cough swabs and induced sputum will be compared to those from FB-BAL. How will this help? If either method is a good alternative to FB-BAL: Less FB-BALs will be needed, reducing disruption to families and NHS costs. Lower airway sampling will be available to more children with PBB enabling targeted antibiotic prescribing and reducing antibiotic resistance. How did patients and the public contribute to this proposal? This study was developed to address the concerns of children and parents about FB-BAL. Three parent representatives and the Alder Hey Young Persons Advisory Group helped with the design. A parent representative is a co-applicant to ensure the study remains patient focused. How will we share the results of this study? Results will be presented at a national / international conference and published in a medical journal. A plain English summary of the results will be sent to all participants

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION