Risk for development of bronchiectasis in patients with Protracted Bacterial Bronchitis Danielle WURZEL1, Julie M MARCHANT1, I Brent MASTERS1, Stephanie YERKOVICH2, John UPHAM3, Anne B CHANG1 1Royal Children’s Hospital, Brisbane, Qld Children’s Medical Research Inst; 2Prince Charles Hospital, Brisbane 3Princess Alexandra Hospital, Brisbane, Australia

BACKGROUND Chronic cough, (duration >4 weeks), is common in children. It is one of the most frequent complaints presenting to primary care physicians.1, 2 In young children, “Protracted Bacterial Bronchitis” “(PBB)” is the most common cause of chronic wet cough.3 PBB likely forms a spectrum with CSLD and bronchiectasis.4 However, to date, there is no published longitudinal data on children with PBB.

MAJOR AIMS AND OBJECTIVES MAJOR AIM: To describe the medium-term outcome of children with PBB OBJECTIVES: To describe the proportion of children who have recurrent episodes of PBB (≥ 3/year) at 1 and 2 years post diagnosis To investigate the proportion who develop bronchiectasis To assess airway impedance (using FOT)

METHODS Protracted Bacterial Bronchitis (PBB) is defined as: Prolonged moist cough lasting >4 weeks Presence of bacterial infection in the airway as detected by Broncho-alveolar lavage (BAL) (>105 CFU/ml) Response (ie resolution of cough) to antibiotic treatment (within 2 weeks) Absence of pointers suggestive of an alternative specific cause of cough Recurrent PBB is defined as ≥ 3 episodes of wet cough treated with and responding to antibiotics over a 12 month period.

COHORT STUDY Prospective recruitment of children with and without cough undergoing bronchoscopy for clinical purposes Patients with history suggestive of suppurative lung disease undergo work-up: Flexible Bronchoscopy + Bronchoalveolar lavage, sweat test, immune function test, nasal ciliary brushing. HRCT chest performed if high clinical suspicion of bronchiectasis. Patients allocated to one of three groups after initial workup: (1) PBB, (2) Bronchiectasis, (3) CSLD, (4) control or other diagnosis

Prospective follow-up of patients with daily cough diary, then monthly contact with caregivers to document episodes of cough, antibiotic use and response to antibiotics At 1 year - patients re-categorised to non-recurrent PBB, recurrent PBB and controls At 2 years – formal clinical assessment (standardised questionnaire/examination/airway impedance (FOT) measurement) to determine the proportion of children who develop bronchiectasis

ANALYSES Primary analysis compared children diagnosed with recurrent PBB and non-recurrent PBB at one-year time-point Secondary analysis compared airway impedance testing (FOT) in children with recurrent PBB vs. controls at 2-year follow-up

RESULTS 166 patients recruited to date (92 PBB, 74 other diagnosis) Median age at recruitment was 23 months (IQR 12, 55); 64% were male Of 72 children with PBB at recruitment: At yr-1 60/72 (83%) had recurrent PBB At yr-2 20/23 (87%) had recurrent PBB (See Figure 1)

FIGURE 1 RECRUITMENT YR 1 YR 2 166 recruited PBB (92) Follow-up (72) 22 166 recruited PBB (92) Follow-up (72) Recurrent PBB (60, 83%) Recurrent PBB (20/23, 87%) Non-recurrent PBB (3/23, 13%) Non-recurrent PBB (12, 17%) Non-recurrent PBB (1/1, 100%) Withdrawn/dropout (20) Bronchiectasis (22) CSLD (3) Control or other dx (49) FIGURE 1 RECRUITMENT YR 1 YR 2 8 9

PRIMARY ANALYSIS Table 1: In children who have completed 1 year follow-up, comparison of children with recurrent PBB vs non-recurrent PBB.

BRONCHIECTASIS DIAGNOSIS 4/72 (≈6%) children with PBB at recruitment were diagnosed with bronchiectasis at 1 yr follow-up.

SECONDARY ANALYSIS Figure 2: Airway impedance measurements (reactance Xrs8Hz and resistance Rrs8Hz) using Forced Oscillatory Technique in children with recurrent PBB v controls at 2-year follow-up

FIGURE 2: Xrs8Hz Rrs8Hz Forced Oscillatory Technique (z-score)

No significance difference in airway impedance, resistance (Rrs8Hz) and reactance (Xrs8Hz), between PBB and controls (p=0.25 and p=0.15 respectively)

con CONCLUSIONS Children diagnosed with PBB are likely to suffer from recurrent episodes of PBB over the subsequent 2 years Males and those with 2 or more siblings are more likely to be have recurrent PBB Preliminary data suggests that recurrent episodes of PBB may be antecedent to later development of bronchiectasis, however further follow-up of this cohort is needed Airway impedance (FOT) is similar in recurrent PBB and control groups (but study in larger group is required)

con REFERENCES Britt H MG, Knox S et al. Bettering the evaluation and care or health: a study of general practice activity. In: Welfare AIoHa, ed.; 2002. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006;129:1S-23S. Marchant JM, Masters IB, Taylor SM, Cox NC, Seymour GJ, Chang AB. Evaluation and outcome of young children with chronic cough. Chest 2006;129:1132-41. 4. Chang AB, Redding GJ, Everard ML. Chronic wet cough: Protracted bronchitis, chronic suppurative lung disease and bronchiectasis. Pediatric pulmonology 2008;43:519-31.

ACKNOWLEDGEMENTS Sophie Anderson-James, Carol Willis, Helen Petsky & Teresa Neylan (Research Assistants) Dr Kerry-Ann O’Grady (Epidemiologist) Claire Shackleton (FOT measurements)

FUNDING DW is funded by TSANZ Allen and Hanbury’s Paediatric Respiratory Medicine Career Development Grant-in-Aid and Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, Australia.