Pulmonary Innate Immunity in Children with Protracted Bacterial Bronchitis Anne B. Chang, PhD 1,2 , Stephanie T. Yerkovich, PhD 3,4 , Peter G. Gibson, MD 5 , Sophie Anderson-James, BSN 1 , Helen L. Petsky, BSN 1 , Melanie L. Carroll, BSc 3 , I. Brent Masters, PhD 1 , Julie M. Marchant, PhD 1 , Danielle Wurzel, MBBS 1 , and John W. Upham, PhD 3 Objective To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human b-defen- sin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutro- philia and infection, and cytokine production of stimulated BAL cells in children with current protracted bacterial bronchitis (PBB), children with resolved PBB (PBB well), and controls. Study design BAL of 102 children (mean age 2.8 years) fulfilling predefined criteria of current PBB (n = 61), PBB well (n = 20), and controls (n = 21) was cultured (quantitative bacteriology) and viruses examined by polymerase chain reaction. hBD2, MBL, and SP-A were measured, and cytokine production by lipopolysaccharide- stimulated BAL cells was determined. Results Median hBD2 and MBL levels were significantly higher in the current PBB group (hBD2 = 164.4, IQR 0-435.5 pg/mL; MBL = 1.7, 0.4-4 ng/mL) than in the PBB well group (hBD2 = 0, IQR 0-85.2; MBL = 0.6, IQR 0.03-2.9) and controls (hBD2 = 3.6, IQR 0-126; MBL = 0.4, IQR 0.02-79). hBD2 was significantly higher in children with airway infection (n = 54; median 76.9, IQR 0-397.3) compared with those without (n = 48; 0, IQR 0-236.3), P = .04. SP-A levels and cytokine production of stimulated BAL cells were similar between groups. Conclusion In children’s airways, hBD2, but not MBL and SP-A, relates to inflammation and infection. In children with PBB, mechanisms involving airway hBD2 and MBL are augmented. These pulmonary innate immunity compo- nents and the ability of BAL cells to respond to stimuli are unlikely to be deficient. (J Pediatr 2012;161:621-25). P rotracted bacterial bronchitis (PBB) is a relatively new and significant diagnostic clinical entity characterized by chronic wet cough and resolution of cough within 2 weeks of treatment with appropriate antibiotics. 1,2 PBB, increasingly rec- ognized as an important pediatric condition worldwide, 2-6 is a common cause of chronic cough in children. 2 Not only is PBB easily treatable (thus improving health-related quality of life 7,8 ) but, if left untreated, it may progress to chronic suppu- rative lung disease and radiological bronchiectasis. 3,7 The lower airways of children with PBB are characterized by bacterial infection and airway neutrophilia. 1,7 The latter suggests that pulmonary innate immunity likely plays a pivotal role. 9,10 However, there are few prospective studies on PBB; only 2 9,10 have evaluated mechanistic links. Innate immune defense involves recognition and clearing responses. In the recognition arm, specific pattern recognition receptors are key components and include Toll-like receptors (TLRs) and lectin-like molecules such as, sur- factant protein-A (SP-A) and mannose-binding lectin (MBL). 11 Pulmonary collectins (eg, SP-A, MBL) play roles in pulmonary innate immunity and regulate inflammatory responses. 12,13 SP-A also has antimicrobial properties. 14 Serum MBL deficiency is associated with bronchiectasis but there is only 1 article on MBL in children’s bronchoalveolar lavage (BAL). Fidler et al 15 reported MBL in the BAL of children with lung infection. The MBL levels were not associated with bacteria or systemic inflammation but correlated with neutrophil elastase. 15 However, quantitative bacteria culture was not defined, polymerase chain reaction for viruses was undertaken in only 4 children, and no other innate immunity components were examined. 15 The clearing mechanism of the innate immune system includes antimicrobials such as the defensin family. In the lungs, epithelial production of b-defensin sub- types 1-3 are likely important. 14,16 In the middle ear, human b-defensin-2 (hBD2) has bactericidal activity against Streptococcus pneumoniae, Moraxella catarrhalis, From the 1 Queensland Children’s Respiratory Centre, and Queensland Children’s Medical Research Institute, Royal Children’s Hospital, Brisbane; 2 Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory; 3 School of Medicine, The University of Queensland; 4 Queensland Centre for Pulmonary Transplantation and Vascular Disease, The Prince Charles Hospital, Brisbane; and 5 Department of Respiratory Medicine, John Hunter Hospital, University of Newcastle, New South Wales, Australia Funded by the Financial Markets Foundation for Children (grant 2010-005) and the Royal Children’s Hospital Foundation. A.C. (grant 545216), P.G. (grant 569240), and J.U. (grant 511019) are supported by National Health and Medical Research Council fellowships. The study sponsors had no role in study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publica- tion. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2012 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2012.03.049 BAL Bronchoalveolar lavage hBD2 Human b-defensin-2 IL Interleukin LPS Lipopolysaccharide MBL Mannose-binding lectin PBB Protracted bacterial bronchitis SP-A Surfactant protein-A TLR Toll-like receptor 621