Chronic Bronchitis in Children and Adults: Definitions, Pathophysiology, Prevalence, Risk Factors, and Consequences.

The complex nature of chronic bronchitis (CB) and changing definitions have contributed to challenges in understanding its aetiology and burden. In children, CB is characterised by persistent airway inflammation often linked to bacterial infections and is therefore termed "protracted bacterial bronchitis" (PBB). Longitudinal studies suggest that CB in childhood persists into adulthood in a subgroup. It can also be associated with future chronic respiratory diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD). Adult CB is traditionally associated with smoking, occupational exposures, and lower socioeconomic status. The interplay between risk factors, childhood CB, adult CB, and other chronic respiratory diseases is intricate, requiring comprehensive longitudinal studies for a clearer understanding of the natural history of CB across the lifespan. Such longitudinal studies have been scarce to date given the logistic challenges of maintaining them over time. In this review, we summarise current evidence on the evolution of the definitions, pathophysiology, risk factors, and consequences of childhood and adulthood chronic bronchitis.

Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation.

Bronchiectasis, particularly in children, is an increasingly recognised yet neglected chronic lung disorder affecting individuals in both low-to-middle and high-income countries. It has a high disease burden and there is substantial inequity within and between settings. Furthermore, compared with other chronic lung diseases, considerably fewer resources are available for children with bronchiectasis. The need to prevent bronchiectasis and to reduce its burden also synchronously aligns with its high prevalence and economic costs to health services and society. Like many chronic lung diseases, bronchiectasis often originates early in childhood, highlighting the importance of reducing the disease burden in children. Concerted efforts are therefore needed to improve disease detection, clinical management and equity of care. Modifiable factors in the causal pathways of bronchiectasis, such as preventing severe and recurrent lower respiratory infections should be addressed, whilst also acknowledging the role played by social determinants of health. Here, we highlight the importance of early recognition/detection and optimal management of bronchiectasis in children, and outline our research, which is attempting to address important clinical knowledge gaps discussed in a recent workshop. The research is grouped under three themes focussing upon primary prevention, improving diagnosis and disease characterisation, and providing better management. Our hope is that others in multiple settings will undertake additional studies in this neglected field to further improve the lives of people with bronchiectasis. We also provide a resource list with links to help inform consumers and healthcare professionals about bronchiectasis and its recognition and management.

Persistent Tachypnoea in Early Infancy: A Clinical Perspective.

Tachypnoea in the newborn is common. It may arise from the many causes of the respiratory distress syndrome such as hyaline membrane disease, transient tachypnoea of the newborn, meconium aspiration etc. Congenital heart disease rarely presents with early tachypnoea on day one or two, in contrast to the early presentation of cyanosis, unless there is "pump" (ventricular) failure such as may occur in a cardiomyopathy/myocarditis, or as a result of severe obstruction to either ventricle. Space-occupying lesions within the chest, for example from a diaphragmatic hernia or a congenital cystic adenomatoid malformation, may present with early tachypnoea, as can a metabolic cause resulting in acidosis. The aim of this paper, however, is to focus on infants where the tachypnoea persists or develops beyond the newborn period, at times with minimal signs but occasionally with serious underlying pathology. They include causes that may have originated in the newborn but then persist; for example, arising from pulmonary hypoplasia or polycythemia. Many congenital cardiac abnormalities, particularly those causing left sided obstructive lesions, or those due to an increasing left to right shunt from large communications between the systemic and pulmonary circulations, need be considered. Respiratory causes, for example arising from aspiration, primary ciliary dyskinesia, cystic fibrosis, or interstitial lung disease, may lead to ongoing tachypnoea. Infective causes such as bronchiolitis or infantile wheeze generally are readily recognisable. Finally, there are a few infants who present with persistent tachypnoea over the first few weeks/months of their life who remain well and have normal investigations with the tachypnoea gradually resolving. How should one approach infants with persistent tachypnoea?

Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. METHODS AND ANALYSIS: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. ETHICS AND DISSEMINATION: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. TRIAL REGISTRATION NUMBER: ACTRN12619000564156.

Mental healthcare for children with chronic conditions: a qualitative study.

OBJECTIVE: To explore parent perspectives on accessing mental healthcare for children with a chronic physical health condition. DESIGN: Qualitative research using semistructured interviews and Framework Analysis. Rankings were used to select attributes for a Discrete Choice Experiment (DCE). SETTING: Four specialty outpatient clinics (diabetes, epilepsy, bronchiectasis unrelated to cystic fibrosis and epidermolysis bullosa) at an Australian tertiary paediatric hospital. PARTICIPANTS: Eighteen parents of children with a chronical physical health condition. RESULTS: Most parents identified the child's general practitioner and/or hospital team as an initial pathway to seek help if they were worried about their child's mental health. Parents see mental healthcare as part of care for the whole child and want the outpatient clinics to proactively discuss child and family mental health, as well as refer to appropriate services as needed. The hospital being a familiar, child-friendly environment was identified as a key reason the hospital might be a desired place to access mental healthcare, as previous research has found. Six attributes of mental health services were identified as important and will be included in an upcoming DCE: travel time, cost, wait time, available hours, knowledge of physical health condition, and recommendation. CONCLUSIONS: This study highlights the opportunity presented in specialist outpatient clinics to address the often unmet mental healthcare needs of children with chronic physical health conditions. Parents identified practical ways for outpatient clinics to better facilitate access to mental healthcare. These will be further explored through a quantitative study of parent preferences.

Quality of life is poorly correlated to lung disease severity in school-aged children with cystic fibrosis.

BACKGROUND: There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic fibrosis (CF). Using data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) we assessed the relationships between HRQOL, lung function and structure. METHODS: 125 children aged 6.5-10 years enrolled in the AREST CF program were included from CF clinics at Royal Children's Hospital (RCH), Melbourne (n = 66) and Perth Children's Hospital (PCH), Perth (n = 59), Australia. Demographics, HRQOL measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R), spirometry, multiple-breath washout (MBW) and chest CT were collected across two years. Correlation between CFQ-R scores and lung structure/function parameters and agreement between parent-proxy and child-reported HRQOL were evaluated. RESULTS: No correlation was observed between most CFQ-R domain scores and FEV1 z-scores, excepting weak-positive correlation with parent CFQ-R Physical (rho = 0.21, CI 0.02-0.37), and Weight (rho = 0.21, CI 0.03-0.38) domain and child Body domain (rho = 0.26, CI 0.00-0.48). No correlation between most CFQ-R domain scores and LCI values was noted excepting weak-negative correlation with parent Respiratory (rho = -0.23, CI -0.41--0.05), Emotional (rho = -0.24, CI -0.43--0.04), and Physical (-0.21, CI -0.39--0.02) domains. Furthermore, structural lung disease on CT data demonstrated little to no association with CFQ-R parent and child domain scores. Additionally, no agreement between child self-report and parent-proxy CFQ-R scores was observed across the majority of domains and visits. CONCLUSION: HRQOL correlated poorly with lung function and structure in early school-aged children with CF, hence clinical trials should consider these outcomes independently when determining study end-points.

Refining diagnostic criteria for paediatric bronchiectasis using low-dose CT scan.

BACKGROUND: There is a current lack of consensus amongst paediatric radiologists and respiratory paediatricians as to the correct CT definition of bronchiectasis in children. Using contemporary low-dose CT, our objectives were to determine the upper limit of normal for broncho-arterial ratio (BAR) in children and to evaluate the effect of age and general anaesthesia. METHODS: Measurements of 330 broncho-arterial ratios from 51 children (0-19 years) undergoing low-dose CT chest for non-respiratory indications were performed by 3 blinded observers (two radiologists, one respiratory physician) using four different methods. Inter-observer reliability, mean BAR and reference ranges (mean±2SD) were calculated. Correlation between age and BARs were examined. Mean BAR for CT under general anaesthesia and CT awake were compared. RESULTS: Inter-observer correlation was extremely high for all measurements (0.93-0.97). There was a weak positive correlation between age and BAR in the CT-awake group (r = 0.33, 95%CI: 0.03-0.57; p = 0.031) using the inner-bronchial wall to artery, short-axis measurement. CT under general anaesthesia showed significantly higher BAR compared to CT-awake [mean difference 0.13 (95%CI: 0.05-0.22; p = 0.004)]. For the CT-awake group, the mean BAR was 0.65 (range: 0.42 to 0.89), with no child having a BAR above 0.9. CONCLUSION: Using a standardised approach, we have shown that a broncho-arterial ratio above 0.9 in children undergoing awake CT is abnormal and suggests airway widening or radiological bronchiectasis. Children undergoing CT under anaesthesia have higher BARs than those undergoing awake CT. A weak positive correlation between broncho-arterial ratio and age was observed, hence, age-adjusted cut-offs for BAR warrant further study.

Absence of human papillomavirus in nasopharyngeal swabs from infants in a population at high risk of human papillomavirus infection.

Maternal urogenital human papillomavirus (HPV) infection may place neonates at risk of HPV acquisition and subsequently lower respiratory infections as HPV can influence development of immunity. The respiratory HPV prevalence is not known in remote-dwelling Aboriginal infants, who are at high risk of respiratory infection and where the population prevalence of urogenital HPV in women is high. These data are necessary to inform HPV vaccination regimens. A retrospective analysis using PCR specific for HPV was performed on 64 stored nasopharyngeal swabs from remote-dwelling Aboriginal infants < 6 months of age, with and without hospitalised pneumonia. HPV DNA was not detected in any specimen. Despite the negative result, we cannot exclude a role for HPV in respiratory infections affecting infants in this population; however, our data do not support HPV as an important contributor to acute respiratory infection in remote-dwelling Aboriginal children.

Outcomes of protracted bacterial bronchitis in children: A 5-year prospective cohort study.

BACKGROUND AND OBJECTIVE: Long-term data on children with PBB has been identified as a research priority. We describe the 5-year outcomes for children with PBB to ascertain the presence of chronic respiratory disease (bronchiectasis, recurrent PBB and asthma) and identify the risk factors for these. METHODS: Prospective cohort study was undertaken at the Queensland Children's Hospital, Brisbane, Australia, of 166 children with PBB and 28 controls (undergoing bronchoscopy for symptoms other than chronic wet cough). Monitoring was by monthly contact via research staff. Clinical review, spirometry and CT chest were performed as clinically indicated. RESULTS: A total of 194 children were included in the analysis. Median duration of follow-up was 59 months (IQR: 50-71 months) post-index PBB episode, 67.5% had ongoing symptoms and 9.6% had bronchiectasis. Significant predictors of bronchiectasis were recurrent PBB in year 1 of follow-up (ORadj = 9.6, 95% CI: 1.8-50.1) and the presence of Haemophilus influenzae in the BAL (ORadj = 5.1, 95% CI: 1.4-19.1). Clinician-diagnosed asthma at final follow-up was present in 27.1% of children with PBB. A significant BDR (FEV1 improvement >12%) was obtained in 63.5% of the children who underwent reversibility testing. Positive allergen-specific IgE (ORadj = 14.8, 95% CI: 2.2-100.8) at baseline and bronchomalacia (ORadj = 5.9, 95% CI: 1.2-29.7) were significant predictors of asthma diagnosis. Spirometry parameters were in the normal range. CONCLUSION: As a significant proportion of children with PBB have ongoing symptoms at 5 years, and outcomes include bronchiectasis and asthma, they should be carefully followed up clinically. Defining biomarkers, endotypes and mechanistic studies elucidating the different outcomes are now required.

Contemporary management of bronchiectasis in children.

Introduction: Bronchiectasis is increasingly recognized as a major cause of morbidity and mortality worldwide. It affects children of all ethnicities and socioeconomic backgrounds and represents a far greater burden than cystic fibrosis (CF). Bronchiectasis often begins in childhood and the radiological changes can be reversed, when mild, with optimal management. As there are limited pediatric studies in this field, current treatment approaches in children are based largely upon adult and/or CF studies. The recent establishment of bronchiectasis registries will improve understanding of pediatric bronchiectasis and increase capacity for large-scale research studies in the future. Areas covered: This review summarizes the current management of bronchiectasis in children and highlights important knowledge gaps and areas for future research. Current treatment approaches are based largely on consensus guidelines from international experts in the field. Studies were identified through searching Medline via the Ovid interface and Pubmed using the search terms 'bronchiectasis' and 'children' or 'pediatric' and 'management' or 'treatments'. Expert opinion: Bronchiectasis is heterogeneous in nature and a one-size-fits-all approach has limitations. Future research should focus on advancing our understanding of the aetiopathogenesis of bronchiectasis. This approach will facilitate development of targetted therapeutic interventions to slow, halt or even reverse bronchiectasis in childhood.

Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children.

Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.

An update on pediatric bronchiectasis.

INTRODUCTION: The prevalence and awareness of bronchiectasis not related to cystic fibrosis (CF) is increasing and it is now recognized as a major cause of respiratory morbidity, mortality and healthcare utilization worldwide. The need to elucidate the early origins of bronchiectasis is increasingly appreciated and has been identified as an important research priority. Current treatments for pediatric bronchiectasis are limited to antimicrobials, airway clearance techniques and vaccination. Several new drugs targeting airway inflammation are currently in development. Areas covered: Current management of pediatric bronchiectasis, including discussion on therapeutics, non-pharmacological interventions and preventative and surveillance strategies are covered in this review. We describe selected adult and pediatric data on bronchiectasis treatments and briefly discuss emerging therapeutics in the field. Expert commentary: Despite the burden of disease, the number of studies evaluating potential treatments for bronchiectasis in children is extremely low and substantially disproportionate to that for CF. Research into the interactions between early life respiratory tract infections and the developing immune system in children is likely to reveal risk factors for bronchiectasis development and inform future preventative and therapeutic strategies. Tailoring interventions to childhood bronchiectasis is imperative to halt the disease in its origins and improve adult outcomes.

Protracted Bacterial Bronchitis in Children: Natural History and Risk Factors for Bronchiectasis.

BACKGROUND: Protracted bacterial bronchitis (PBB) and bronchiectasis are distinct diagnostic entities that share common clinical and laboratory features. It is postulated, but remains unproved, that PBB precedes a diagnosis of bronchiectasis in a subgroup of children. In a cohort of children with PBB, our objectives were to (1) determine the medium-term risk of bronchiectasis and (2) identify risk factors for bronchiectasis and recurrent episodes of PBB. METHODS: One hundred sixty-one children with PBB and 25 control subjects were prospectively recruited to this cohort study. A subset of 106 children was followed for 2 years. Flexible bronchoscopy, BAL, and basic immune function tests were performed. Chest CT was undertaken if clinical features were suggestive of bronchiectasis. RESULTS: Of 161 children with PBB (66% boys), 13 were diagnosed with bronchiectasis over the study period (8.1%). Almost one-half with PBB (43.5%) had recurrent episodes (> 3/y). Major risk factors for bronchiectasis included lower airway infection with Haemophilus influenzae (recovered in BAL fluid) (P = .013) and recurrent episodes of PBB (P = .003). H influenzae infection conferred a more than seven times higher risk of bronchiectasis (hazard ratio, 7.55; 95% CI, 1.66-34.28; P = .009) compared with no H influenzae infection. The majority of isolates (82%) were nontypeable H influenzae. No risk factors for recurrent PBB were identified. CONCLUSIONS: PBB is associated with a future diagnosis of bronchiectasis in a subgroup of children. Lower airway infection with H influenzae and recurrent PBB are significant predictors. Clinicians should be cognizant of the relationship between PBB and bronchiectasis, and appropriate follow-up measures should be taken in those with risk factors.

Adenovirus species C is associated with chronic suppurative lung diseases in children.

BACKGROUND: The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). METHODS: Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. RESULTS: Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). CONCLUSIONS: HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.

Prospective characterization of protracted bacterial bronchitis in children.

BACKGROUND: Prior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection. METHODS: Children with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture. RESULTS: The median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L). CONCLUSIONS: Children with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.

Wet cough in children: infective and inflammatory characteristics in broncho-alveolar lavage fluid.

Wet cough is a common feature of many disease processes affecting children. Our aim was to examine the relationships between cough nature, lower airway infection (bacterial, viral, and viral-bacterial) and severity of neutrophilic airway inflammation. We hypothesized that viral-bacterial co-infection of the lower airway would be associated with wet cough and heightened neutrophilic airway inflammation. We prospectively recruited 232 children undergoing elective flexible bronchoscopy. Participants were grouped using a cough nature symptom-based approach, into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature, and duration of cough and key demographic factors, were collected. Children with wet cough (n = 143) were more likely to have lower airway bacterial infection (OR 2.6, P = 0.001), viral infection (OR 2.04, P = 0.045) and viral-bacterial co-infection (OR 2.65, P = 0.042) compared to those without wet cough. Wet cough was associated with heightened airway neutrophilia (median 19%) as compared to dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18%, and 6%, respectively, P < 0.0001). Children with wet cough had higher rates of lower airway infection with bacteria and viruses. Maximal neutrophilic airway inflammation was seen in those with viral-bacterial co-infection. Cough nature may be a useful indicator of infection and inflammation of the lower airways in children.

A case for early bronchoscopic airway assessment after disc battery ingestion.

Disc battery ingestion in children is becoming increasingly common with the proliferation of small battery-powered electronic devices. In the case of esophageal impaction, the likelihood and severity of complications are proportionate to the time between ingestion and removal. Tracheo-esophageal fistulae (TOF) are a recognized complication and can be life-threatening. We describe an interesting case of disc battery ingestion with delayed recognition of a TOF. We document the tracheal mucosal healing process of a large airway defect and describe the role of bronchoscopy in guiding the timing of surgical intervention. This case highlights the important role of early bronchoscopic assessment in management of these patients.

Respiratory virus detection in nasopharyngeal aspirate versus bronchoalveolar lavage is dependent on virus type in children with chronic respiratory symptoms.

BACKGROUND: The comparative yield of respiratory virus detection from nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain. Furthermore, the significance of virus detection and its relationship to lower airway neutrophilic inflammation is poorly studied. OBJECTIVES: To evaluate the sensitivity, specificity and predictive values of NPA for detecting respiratory viruses in BAL; and to determine the relationship between viruses and lower airway neutrophilia in children with non-acute respiratory illness. STUDY DESIGN: 150 paired NPA and BAL samples were obtained from 75 children aged <18 years undergoing flexible bronchoscopy for investigation of chronic respiratory symptoms. Viral studies were performed using polymerase chain reaction (PCR). Cellularity studies were performed on BALs. Diagnostic parameters of NPA compared to BAL and associations between viruses and lower airway %neutrophils were evaluated. RESULTS: NPA had a higher yield than BAL for detection of any respiratory virus (52 versus 38, respectively). NPA had a high sensitivity (92%) and low specificity (57%) for detecting HRV in BAL with poor kappa agreement value of 0.398 (95% CI 0.218-0.578, p<0.001). NPA had a fair sensitivity (69%) and good specificity (90.3%) for detecting HAdV on BAL, kappa agreement was 0.561 (95% CI 0.321-0.801, p<0.001). HAdV positivity on NPA, compared to negativity, was independently associated with heightened airway neutrophilia [mean difference (95% CI): 18 (1,35); p=0.042]. CONCLUSIONS: NPA has a higher yield for respiratory virus detection than BAL, however its diagnostic accuracy is dependent on viral species. Adenovirus positivity is associated with significantly heightened lower airway neutrophilia in children with chronic respiratory symptoms.

Pulmonary innate immunity in children with protracted bacterial bronchitis.

OBJECTIVE: To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human ß-defensin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutrophilia 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 components and the ability of BAL cells to respond to stimuli are unlikely to be deficient.