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Objectives: To describe characteristics and outcomes of children requiring intensive care therapy (ICT) within 12 hours following a medical emergency team (MET) event. Design: Retrospective cohort study. Setting: Quaternary paediatric hospital. Patients: Children experiencing a MET event. Measurements and main results: Between July 2017 and March 2019, 890 MET events occurred in 566 patients over 631 admissions. Admission to intensive care followed 183/890 (21%) MET events. 76/183 (42%) patients required ICT, defined as positive pressure ventilation or vasoactive support in intensive care, within 12 hours. Older children had a lower risk of requiring ICT than infants aged < 1 year (age 1-5 years [risk difference, -6.4%; 95% CI, -11% to -1.6%; P = 0.01] v age > 5 years [risk difference, -8.0%; 95% CI, -12% to -3.8%; P < 0.001]), while experiencing a critical event increased this risk (risk difference, 16%; 95% CI, 3.3-29%; P = 0.01). The duration of respiratory support and intensive care length of stay was approximately double in patients requiring ICT (ratio of geometric means, 2.0 [95% CI, 1.4-3.0] v 2.1 [95% CI, 1.5-2.8]; P < 0.001) and the intensive care mortality increased (risk difference, 9.6%; 95% CI, 2.4-17%; P = 0.01). Heart rate, oxygen saturation and respiratory rate were the most commonly measured vital signs in the 6 hours before the MET event. Conclusions: Approximately one-fifth of MET events resulted in intensive care admission and nearly half of these required ICT within 12 hours. This group had greater duration of respiratory support, intensive care and hospital length of stay, and higher mortality. Age < 1 year and a critical event increased the risk of ICT.

Background: For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. Method(s): This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. Result(s): The main predictor of future BMD was the previous BMD Z score (p <.001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1, and number of hospital admissions. Conclusion(s): Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.Copyright © 2021 Wiley Periodicals LLC

BACKGROUND: For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. METHODS: This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. RESULTS: The main predictor of future BMD was the previous BMD Z score (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. CONCLUSION: Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB). Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study. 99 out of 157 ACFBAL children (mean+/-SD age 13+/-1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years. The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.Copyright © ERS 2020

Background: Both infection and inflammation are critical to the progression of cystic fibrosis (CF) lung disease. Potential anatomical differences in lower airway infection, inflammation and bronchiectasis in young children with CF raise questions regarding the pathogenesis of early structural lung disease. Method(s): A longitudinal multi-centre birth cohort study of infants newly diagnosed with CF was conducted. Paired bronchoalveolar lavage (BAL) samples were obtained from the right middle lobe (RML) and lingula bronchi. Chest computed tomography (CT) was performed biennially and analysed using the modified CF-CT scoring system. Result(s): One hundred and twenty-four children (0.11 - 7.0 years) contributed 527 BAL samples and underwent 388 CT chest scans. Pro-inflammatory microbes were detected in 279 BAL samples (53%), either in both lingula and RML samples (69%), in the lingula alone (24%), or in the RML alone in only 7% of samples. Overall, the prevalence of structural lung disease was greater in the setting of pro-inflammatory microbes. Although infection was less commonly isolated in the right lung, bronchiectasis was more commonly detected in the right lung compared with the left. No anatomical differences in the presence of air trapping were detected. Conclusion(s): Overall, the detection of pro-inflammatory microbes in the lower airways was associated with increased risk of both air trapping and bronchiectasis. However, the apparent discordance between commonest sites of isolation of pro-inflammatory microbes and the anatomical site of early bronchiectasis warrants further exploration.Copyright © 2019 European Cystic Fibrosis Society

BACKGROUND: Serum Glycoprotein A (GlycA) levels are increased in a variety of inflammatory disease states. However, GlycA has not been previously evaluated in children with cystic fibrosis (CF). We assessed the relationship between GlycA and pulmonary infection, inflammation, bronchial wall thickening (BWT) and bronchiectasis in young children with CF. METHODS: From 95 patients, we obtained 311 paired serum and bronchoalveolar lavage (BAL) samples at multiple timepoints, with concurrent chest computed tomography on 168 occasions. Quantitative GlycA was determined using high-throughput nuclear magnetic resonance metabolomic testing. Participants were considered to be infected if ≥1 significant proinflammatory organism was isolated from their BAL. The presence of free neutrophil elastase (NE) above the limit of detection was considered evidence of inflammation. The relationships between GlycA levels and infection state, inflammation, and bronchiectasis were examined using a generalized estimating equation approach. RESULTS: There was a positive relationship between GlycA (mean 1.01 mmol/L, range 0.68-1.92 mmol/L) and being infected with one or more proinflammatory organisms, even after adjusting for age and gender (odds ratio [OR], 1.2 per 0.1 mmol/L, 95% confidence interval [CI], 1.02, 1.4, P = .03). There was also a positive relationship between GlycA and NE (unadjusted OR, 1.2 95% CI, 1.01, 1.4, P = .04), not significant after adjustment. GlycA concentration was associated with BWT but not bronchiectasis. CONCLUSIONS: Although GlycA levels were higher on average in those who had an infection or neutrophilic inflammation, there was also considerable variability, limiting the clinical utility of this biomarker alone in determining early disease status in CF.

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.

BACKGROUND AND AIM: Polyethylene glycol (PEG) is the gold standard for fecal disimpaction in constipation. A regimen of PEG combined with the stimulant laxative sodium picosulphate (SPS) produced fecal disimpaction in chronically constipated children in the community, but it is unknown if it is effective for more severe constipation. To determine the stool output and effect of a combined PEG and SPS regimen on fecaloma in children with severe constipation and impaction. METHODS: Children with symptoms for a duration of ≥2 years, a palpable fecaloma, and enlarged rectum on X-ray (rectal: pelvic ratio > 0.6) were recruited from a tertiary hospital. Daily diaries recorded laxative dose, stool frequency, volume, and consistency (Bristol stool scale, BSS). Abdominal X-rays were taken on day 1 and day 8, and stool loading was assessed using the Leech score. Laxative doses were based on the child's age. The dose of PEG with electrolytes taken was 2-8 sachets (14.7 g/sachet) on days 1-2, reducing to 2-6 sachets on day 3. The SPS dose was 15-20 drops on days 2-3. RESULTS: Eighty-nine children (4-18 years) produced a large volume of soft stool (median/inter-quartile-range: 2.2/1.6-3.1 L) over 7 days. Stool volume on X-rays decreased significantly in the colon (P < 0.001). Fecalomas resolved in 40 of 89 children, while 49 needed a second high dose. Rectal:pelvic ratios did not change. CONCLUSIONS: A combined high dose of PEG and SPS on days 1 and 2 was effective in removing the fecaloma in half of the children. Administering high doses for a longer period should be tested to provide outpatient disimpaction for severe fecalomas. Rectums remained flaccid after emptying.

AIM: The aims of this study were to estimate the proportion of emergency department presentations attributable to children with cerebral palsy (CP), investigate the frequency of emergency department presentations in a CP cohort, and compare emergency department presentations among children with CP with those of other children. METHOD: This was a retrospective cohort study. The Victorian Cerebral Palsy Register was linked to the Victorian Emergency Minimum Dataset. Data on emergency department presentations for the CP cohort occurring between 2007 and 2014 and population control data were obtained. RESULTS: The CP cohort (n=1748) had 7015 emergency department presentations during the 7-year period, accounting for 0.4% of the 1.69 million age-specific presentations during that time. The number of annual presentations per 1000 children rose with increasing CP severity. Compared with presentations among the general population, higher proportions of presentations among the CP cohort were preceded by ambulance arrivals (27% vs 8%), triaged as urgent (66% vs 32%), and required hospital admission (38% vs 12%). INTERPRETATION: The marked differences in presentations between the CP cohort and the general population in the proportions that were urgent and required ambulance arrivals and hospital admissions was an important finding. Strategies to ensure appropriate use of services, including encouragement to seek earlier assistance from primary care providers, may prevent problems escalating to the need for urgent care. WHAT THIS PAPER ADDS: Children with cerebral palsy (CP) account for 0.4% of childhood emergency department presentations. More emergency department presentations among children with CP require ambulance arrival. More CP emergency department presentations are urgent and require hospital admission. Traditional emergency department triage scales seem less accurate for this group.

AIM: The overall aim was to investigate the feasibility and utility of linking a cerebral palsy (CP) register to an administrative data set for health services research purposes. We sought to compare CP hospital admissions to general childhood population admissions, and identify factors associated with type and frequency of admissions in a CP cohort. METHOD: The CP register for Victoria, Australia was linked to the state's hospital admissions database. Data pertaining to the admissions of a CP cohort (n=1748) that took place between 2007 and 2014 were extracted. Population data were also obtained. RESULTS: Overall, 80% of the CP cohort (n=1401) had at least admission between 2007 and 2014, accounting for 11 012 admissions or 1.5% of all admissions in their age group. Compared to general population admissions, CP admissions were more costly and more likely to be elective (66% vs 57%; p<0.001), medical (71% vs 57%; p<0.001), and to take place in metropolitan hospitals (92% vs 78%; p<0.001). Increased CP severity and complexity were associated with having more admissions and a higher proportion of admissions attributable to respiratory illness. INTERPRETATION: By linking with administrative data sets, CP registers may be useful for health services research and inform health service delivery.

Purpose: Childhood idiopathic pulmonary arterial hypertension (IPAH) is a rare disease. Population-based incidence and long-term outcomes are not well described. We describe the incidence and outcomes of this population using a bi-national multicenter registry. Method(s): The Pediatric Pulmonary Hypertension Registry (PPHR) is a collaboration between 9 Australian and New Zealand centers from 1/1/2002 to 12/31/2013. Children 3 months to 18 years at diagnosis of IPAH were included with retro- and prospective data entry. Participating center institutional review boards approval and informed consent were obtained. Population-based incidence was calculated. Primary study end-points were death or lung transplantation, with secondary end-point of parenteral prostanoid- free survival. Result(s): Forty-three patients, 12 with family history of IPAH, satisfied entry criteria for PPHR; median [IQR] age at diagnosis 8.7 years [4.8, 14] and 51% were female. Overall bi-national childhood IPAH incidence was 6.4 per 10 million person-years, with a peak incidence in the 10-14yo age group (8.7 per 10 million person-years). Almost all patients were symptomatic at diagnosis, with 31/42 (74%) WHO class II or III, and 8/42 (19%) WHO class IV. Targeted pulmonary vasodilator therapy was commenced in all but 4/43 (9%) patients in the cohort, and parenteral prostenoid used in 15/43 (35%) patients. Of 43 PPHR patients, 17 (40%) achieved the combined end-point of death/transplantation, with median [IQR] follow-up 3.3 years [0.44, 5.9]. Transplantation-free survival was 83% (95%CI 68-92%) 1 year after diagnosis and 56% (37-70%) at 5 years. Freedom from parenteral prostanoid, death and transplantation was 68% (95%CI 43-84%) at 1 year, 44% (21- 65%) at 2 years and 31% (12-53%) at 5 years in the eligible PPHR population. Demographic, symptomatology, echocardiographic and hemodynamic parameters were assessed for association with death/transplantation in univariable analysis. Of these, only female g

Purpose: Childhood idiopathic pulmonary arterial hypertension (IPAH) is characterized by elevated pulmonary vascular resistance. Care in specialized centers may result in better outcomes for these patients than standard care. Method(s): The Pediatric Pulmonary Hypertension Registry (PPHR) is a collaboration between 9 Australian and New Zealand hospitals from 1/1/2002 to 12/31/2013, enrolling patients 3 months to 18 years old at diagnosis. Children diagnosed before 2002 were included as historic controls. Expert center care was multidisciplinary, with specialized clinicians, nursing, social work and targeted pulmonary vasodilators including prostanoids. Standard centers provided usual medical care. Primary study end-points were death or lung transplantation, with targeted therapies and center specialization as secondary end-points. Result(s): Three of 9 PPHR hospitals were expert centers and managed 23 patients, 20 received standard care in other centers, and 15 historic control patients were managed before 2002. There was no difference in baseline parameters between the current era groups. Transplant-free survival was improved in expert compared to standard centers at 1 year post-diagnosis (p= 0.044). Fewer patients died in expert centers than historic controls (4/23 (17%) vs 8/15 (53%) p= 0.033), while the proportion of deaths in standard care centers (9/20 (45%)) was closer to the proportion for historic controls. Four patients underwent lung transplantation, 1 from a non-expert center. Expert center patients had the highest transplant-free survival of 95% (95% CI 72-99%) 1 year and 60% (33-78%) 5 years after diagnosis (P< .007 vs historic controls). Transplant-free survival in standard care centres was 70% (95% CI 45-85%) 1 year after diagnosis and 50% (25-71%) at 5 years; in historic controls transplant-free survival was 53% (95% CI 26-74%) 1 year and 33% (12-56%) 5 years after diagnosis. Combination therapy was more common in expert center patients (12/23, 52%)

Background: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged <=. 5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. Method(s): Of 168 CF children aged <=. 5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. Result(s): Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. Conclusion(s): CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children.Copyright © 2014 European Cystic Fibrosis Society.

AIM: To evaluate the reliability, validity and responsiveness of the High-level Mobility Assessment Tool (HiMAT) in children and adolescents with traumatic brain injury (TBI) and to compare the mobility skills of children with TBI to those of healthy peers. METHOD: The mobility skills of 52 children with moderate and severe TBI (36 males; mean age = 12 years, range = 6-17) were assessed using the HiMAT and the Pediatric Evaluation of Disability Inventory (PEDI). Inter-rater reliability, re-test reliability and responsiveness of the HiMAT were evaluated in sub-groups by comparing results scored at several time-points. The HiMAT scores of children with TBI were compared with those of a healthy comparative cohort. RESULTS: The HiMAT demonstrated excellent inter-rater reliability (ICC = 0.93), re-test reliability (ICC = 0.98) and responsiveness to change (p = 0.002). The PEDI demonstrated a ceiling effect in mobility assessment of ambulant children with TBI. The HiMAT scores of children with TBI were lower than those of their healthy peers (p < 0.001). INTERPRETATION: The HiMAT is a reliable, valid and sensitive measure of high-level mobility skills following childhood TBI. The high-level mobility skills of children with TBI are less proficient than their peers.

Objectives To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Study design Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Results Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P =.90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P =.48). Conclusions BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings. Copyright © 2014 Elsevier Inc. All rights reserved.

BACKGROUND: Use of inhaled tobramycin therapy for treatment of Pseudomonas aeruginosa infections in young children with cystic fibrosis (CF) is increasing. Safety data for pre-school children are sparse. METHODS: The aim of this study was to assess the safety of tobramycin solution for inhalation (TOBI®-TSI) administered twice daily for 2 months/course concurrently to intravenous (IV) tobramycin during P. aeruginosa eradication therapy in children (0-5 years). Audiological assessment and estimation of glomerular filtration rate (GFR) was measured prior to any exposure and end of the study. RESULTS: Data were available from 142 patients who were either never exposed to aminoglycosides (n=39), exposed to IV aminoglycosides only (n=36) or exposed to IV+TSI (n=67). Median exposure to TSI was 113 days [59, 119]. Comparison of effects on audiometry results and GFR, showed no detectable difference between the groups. CONCLUSIONS: Use of TSI and IV tobramycin in pre-school children with CF was not associated with detectable renal toxicity or ototoxicity.

Background Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Methods Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. Results 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospitalmanaged exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05). Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.

Background: Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Method(s): Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. Result(s): 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05). Conclusion(s): Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group. Copyright Article author (or their employer) 2013.

Objective: Our aim was to determine the safety of BAL in young children <6 years with CF. Method(s): As part of a multi-center study of BAL-directed therapy, children with CF <6 years had one or more BALs between September 1999 and December 2005. Adverse events were recorded intraoperatively and for 24 hr thereafter. Clinical characteristics before BAL, findings at bronchoscopy and BAL results were assessed as risk factors for adverse events. Result(s): 333 BALs were conducted in 107 (56 males) children, median age 23.5 (range 1.6-67.5) months, including 170 (51%) for pulmonary exacerbation. 29 BALs (8.7%) were followed by fever >=38.5degreeC and 10 (3%) had clinically significant episodes (five intraoperative hemoglobin desaturations to <90% requiring intervention, one tachyarrhythmia, two needing post-operative supplemental oxygen, one hospitalization for stridor). Two contaminated bronchoscopes were detected. 180 minor adverse events were recorded in 174 (52%) BAL procedures (137 altered cough, 41 fever <38.5degreeC). Low percentage BAL return (P = 0.002) and focal bronchitis (P = 0.02) were associated with clinically significant deterioration. Multivariable analysis identified Streptococcus pneumoniae (OR 22.3; 95% confidence interval (CI); 6.9,72), Pseudomonas aeruginosa (OR 2.4; 95% CI 1.0, 5.8), respiratory signs (OR 5.0; 95% CI 1.7, 14.6) and focal bronchitis (OR 5.9; 95% CI 1.2, 29.8) as independent risk factors for post-bronchoscopy fever >=38.5degreeC. Conclusion(s): Adverse events are common with BAL in young CF children, but are usually transient and well tolerated. Parents should be counseled that signs of a pre-existing lower respiratory infection are associated with increased risk of post-BAL fever. © 2008 Wiley-Liss, Inc.