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Purpose Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis–related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. Methods Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. Results The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. Conclusion We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH). It involves a large, Canadian prospective (2005-2017) observational multicenter study of children at high risk for RSV infection. A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); "miscellaneous" (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The "miscellaneous" group increased over time (4.4% in 2005-2006 to 22.5% in 2016-2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged2 years, multiple conditions, and a residual "unclassified" group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4-18.2; Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required.· Main indications were prematurity (63.3%); "miscellaneous" (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%).. · The proportion of children in the "miscellaneous" group, comprised of those with trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged2 years, multiple conditions, and a residual "unclassified" group, increased over time (4.4% in 2005-2006 to 22.5% in 2016-2017).. · Respiratory illness-related hospitalization occurred in 2,054 children (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH: 1.6%)..

Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. For population studies, phase is often inferred from external data but read-based phasing approaches that span long genomic distances would be more accurate because they enable both genotype and phase to be obtained from a single dataset. To demonstrate how read-based phasing can provide functional insights, we sequenced 477 individuals with Cystic Fibrosis (CF) using linked-read sequencing. We benchmark read-based phasing with different short- and long-read sequencing technologies, prioritize linked-read technology as the most informative and produce a benchmark phase call set from reference sample HG002 for the community. The 477 samples display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, which facilitates understanding of complex CF alleles. Fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus demonstrates a 20 kb deletion and a PRSS2 missense variant p.Thr8Ile (rs62473563) independently contribute to meconium ileus risk (p=0.0028, p=0.011, respectively) and are PRSS2 pancreas eQTLs (p=9.5e-7 and p=1.4e-4, respectively), explaining the mechanism by which these polymorphisms contribute to CF. Phase enables access to haplotypes that can be used for genome graph or reference panel construction, identification of cis-effects, and for understanding disease associated loci. The phase information from linked-reads provides a causal explanation for variation at a CF-relevant locus which also has implications for the genetic basis of non-CF pancreatitis to which this locus has been reported to contribute.

BACKGROUND AND OBJECTIVES Cystic fibrosis (CF) screen–positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. METHODS Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive–screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. RESULTS The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. CONCLUSIONS Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

Background Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF. Methods In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016. Results Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8–206.2) vs. 75.0 (61.0–105.9); P n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3–126.8) vs. 73.7(60.0–96.0); P = 0.02). Conclusions Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID.

Background. Community-acquired pneumonia (CAP) is common within pediatrics and contributes disproportionately to morbidity and mortality. Necrotizing pneumonia is a well-documented complication of CAP. It is thought to be caused by necrosis and liquefaction of consolidated lung and can result in damage to lung parenchyma, including pneumatocele development. Management of necrotizing pneumonia with pneumatocele may include hospitalization, intensive care unit admission, and lengthy antibiotic courses. Severe cases may need invasive procedures. Case Presentation. We present a case of severe necrotizing pneumonia requiring prolonged venovenous extracorporeal membrane oxygenation (V-V ECMO) with development of persistent pneumatoceles, requiring pneumonectomy while on ECMO support to allow for decannulation and extubation. Conclusions. In critically ill patients with extensive unilateral necrotizing pneumonia with pneumatocele development, surgical intervention can be considered when attempts to wean ventilation have been unsuccessful. This case provides evidence that V-V ECMO and pneumonectomy is a viable salvage therapy in the most critically unwell children.

Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes.Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies.The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies.We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged

Background Airway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation. Methods Surfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD). Results CF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products. Conclusion We confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF.

Background: Caring for children with a tracheostomy at home may reduce costs. Prior to tracheostomy, in our institution, children may be cared for in inpatient (IP) wards or PICU. After tracheostomy, initial care occurs in PICU, then in a special section of IP area before transfer home. We initiated QI to improve care and shorten length of stay. We noted current classifications of indications for tracheostomy are based on anatomic/pathological findings, of limited value in QI. Objective: To review indications for tracheostomy and develop a classification system To map a child’s progress using this classification To use this data to identify opportunities for QI Methods: Tracheostomies were created in 100 children from 2005 to 2017, and we summarised the indications thus: Isolated airway anomaly (e.g. subglottic stenosis ), n=51 Complex syndrome with airway anomalies (e.g. Treacher Collins Syndrome) n=21 Tracheostomy to allow invasive ventilation (e.g. neuromuscular disease). N= 28 Results: Time (days) in different parts of our institution Conclusion: Categorization of indication for tracheostomy proved useful in QI. This categorization can be used by others to address service needs and compare programs

Introduction Esophageal atresia/tracheoesophageal atresia (EA/TEF) is a multisystem congenital anomaly. Initial treatment is complex and ongoing complications are numerous. Coordination of care has been shown to reduce costs and hospitalizations in complex populations. A previous study at our center demonstrated that children with EA/TEF lacked coordinated care. A multidisciplinary clinic was established to provide coordinated care, screen for complications, provide anticipatory guidance, and improve outpatient access. Methods This single-center retrospective cohort study included children with EA/TEF born between March 2005 and March 2011 and enrolled in the clinic. Patients with EA alone were excluded. A chart review was completed to identify demographics, hospitalizations, emergency visits, clinic visits, coordination of outpatient care, and adherence to the intended clinic schedule. Results Twenty-five patients were included; 84% had a C-type EA/TEF. Multidisciplinary clinics had an average of 4.3 health care providers (1.75 physicians) per visit. Adherence to the visit schedule was 91.4%. The average length of stay (46.2 + 37.9 days) for the initial hospital admission was similar to the previous study cohort. Subsequent hospital admissions were reduced in number and length of stay, most notably in the first two years of life (0–1 year: 1.28 + 1.2 admissions/patient; 10.7 + 19.1 days/admission; 1–2 years: 0.6 + 0.76 admissions/patient; 3.7 + 3.2 days/admission). Conclusions Multidisciplinary care clinics for medically complex children such as those with EA/TEF can improve care through coordination of visits with multiple health care providers and may contribute to reduced use of acute care services.

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study’s objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged

OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; “CF screen positive, inconclusive diagnosis” [CFSPID]) for disease manifestations. METHODS: Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life. RESULTS: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61–106] vs 144 [105–199] μg/L; P Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride ( P P = .009) levels than did CFSPID→CFSPID patients. CONCLUSIONS: A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.

Objectives Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. Methods We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Results Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Conclusions Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.

Croup develops in more than 80 000 Canadian children each year, making it the second most common cause of respiratory distress in the first decade of life.[1][1],[2][2] It affects boys more than girls (1.4:1) and young children between 6 months and 3 years of age more commonly than younger infants

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of autonomic dysregulation, characterized by alveolar hypoventilation especially during sleep. As a result, lifelong ventilatory assistance is necessary in these patients. Many infants and children initially require positive pressure ventilation via tracheostomy for support. Associated complications and psychosocial pressure may prompt early transition to non-invasive ventilation. We present the details of a patient with CCHS who successfully transitioned from tracheostomy to bilevel positive airway pressure ventilation at an early age of 3 years.

Introduction : Surfactant dysfunction in cystic fibrosis contributes to longitudinal declines in pulmonary function and susceptibility to infection. The cause of the dysfunction is not fully understood. Aims and objectives: To determine the role of cholesterol and oxidation of unsaturated phospholipids in surfactant dysfunction and to attempt reversal of the dysfunction with methyl-β-cyclodextrin (MβCD). Methods : Surfactant was extracted from surplus broncho-alveolar lavage (BAL) fluid obtained for routine diagnostic purposes in a paediatric population of CF patients. BAL from lung healthy children was used as control. Surfactant function was measured in a captive bubble surfactometer (CBS). Cultures for microbial pathogens, differential cell counts and lipid biochemistry were assayed. Results : Cholesterol concentration and neutrophils were significantly elevated in the CF BAL compared to controls. Surfactant function was markedly impaired in all but 3 of the 25 CF children. Surfactant from 16 CF children with dysfunctional surfactant were retested after incubation with MβCD; 14 of 16 were restored to normal function. In vitro mechanistic studies revealed that the dysfunction could be attributed to both excess cholesterol and an interaction between cholesterol, oxidized phospholipids and pro-inflammatory hydrolysis products of phosphatidylcholine; free fatty acids and lysophosphatidylcholine. Conclusion : This study reveals a previously unappreciated consequence of disturbance in pulmonary lipid homeostasis in causing surfactant dysfunction in cystic fibrosis. The dysfunction can be reversed in vitro in a majority of patients with a drug that sequesters lipids. Funded by AIHS/CRIO.

Objective The objective was to derive a simple clinical scoring instrument for assessing children with croup by telephone for use in clinical research studies. Methods We reviewed published literature on croup scores, surveyed experienced pediatric emergency nurses and physicians, and conducted a prospective cohort study. Score items were derived from published literature and surveys of experienced clinicians. We enrolled children with croup attending an urban pediatric emergency department. Families of children enrolled were contacted daily by telephone and asked standardized questions about their child's clinical symptoms and family functioning. Data from this survey were used to derive the clinical score. Results We identified 11 unique croup scores from the literature and interviewed 6 experienced clinicians. We enrolled 330 children and achieved complete follow-up for 301. Of the various groupings of items and duration of assessment, the 2-item score (barky cough and stridor) was the simplest and most reliable. Three days of follow-up yielded optimal correlations. Conclusions We derived a 2-item Telephone Out Patient score assessed daily for 3 days after an emergency department visit. Validation of this score in a future, independent prospective cohort is needed.

Background Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine (NE) may prevent intubation. Objectives To evaluate the efficacy and safety of NE in children presenting to emergency department (ED) or admitted to hospital with croup. Search methods We searched CENTRAL (The Cochrane Library 2010, Issue 4), containing the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (1966 to November Week 1, 2010), EMBASE (1980 to November 2010), Web of Science (1974 to November 2010), CINAHL (1982 to November 2010) and Scopus (1996 to November 2010). Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: NE versus placebo, racemic NE versus L-epinephrine (an isomer), and NE delivered by intermittent positive pressure breathing (IPPB) versus NE without IPPB. Primary outcome was change in croup score post-treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects. Data collection and analysis Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodologic quality assessment. One author extracted data while the second checked accuracy. We performed standard statistical analyses. Main results Eight studies (225 participants) were included. NE was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I2 statistic = 0%). This effect was not significant two and six hours post-treatment. NE was associated with significantly shorter hospital stay than placebo (one RCT, mean difference -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of NE via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42). Authors' conclusions NE is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or LE, or IPPB over simple nebulization. Plain Language Summary Nebulized epinephrine for croup in children Croup is a common childhood illness that is usually caused by a viral infection. Symptoms of croup include a hoarse voice, a 'barking' cough and noisy breathing. These symptoms are the result of swelling that occurs in the area of the windpipe (trachea) just below the voice box (larynx). Although most cases of croup are mild and resolve on their own, occasionally the swelling can be severe enough to cause difficulty in breathing. In these children, epinephrine (also called adrenaline) is a medication that is inhaled as a mist to temporarily shrink the swollen area in the trachea. This review looked at trials of inhaled epinephrine for the treatment of children with croup. Compared to no medication, inhaled epinephrine improved croup symptoms in children at 30 minutes following treatment (three studies, 94 children). This treatment effect disappeared two hours after treatment (one study, 20 children). However, children's symptoms did not become worse than prior to treatment. No study measured adverse events. This review is comprised of only eight studies and the number of included children was small (225). Few studies examined similar outcomes, therefore data could often not be pooled and conclusions are based on one or few studies.

Background Asthma is characterized by chronic airway inflammation and affects many children. One treatment option used to control asthma symptoms is the class of medications known as the long acting β2-agonists (LABA) and they are often used in combination with inhaled corticosteroids (ICS). The use of LABA in children has been widely debated in the literature. Objectives To synthesize the evidence currently in the Cochrane Library of systematic reviews related to the question: ‘In children with symptomatic asthma, does treatment with a LABA as a primary or add-on therapy to ICS improve objective measures of lung function and asthma symptom control, reduce exacerbations, and improve quality of life?’. Methods The Cochrane Database of Systematic Reviews was searched using the term ‘asthma’ in the title for all systematic reviews examining LABA vs any other pharmacological agent for the treatment of asthma. Data were extracted and entered into tables; syntheses occurred using qualitative and quantitative methods. Main Results Seven reviews were identified; however, only four reviews contained data for children. There was no significant difference in the asthma exacerbations among those treated with LABA or any other treatment. For those treated with LABA with no/varied ICS vs placebo with no/varied ICS, there was a significant improvement in percent predicted forced expiratory volume in the first second (FEV1) and a significant number of children had a ≥ 15% increase in FEV1. There was also a significant reduction in the change in whole day rescue medication, fewer asthma related night-time wakenings, and lower symptom scores for LABA with no/varied ICS. Change in FEV1 (Litres (L) or percent predicted) and improvement in morning and evening peak expiratory flow (PEF) favoured LABA and ICS vs fixed dose ICS and placebo. There was a significantly higher risk of adverse events among those receiving LABA and ICS compared to ICS with or without placebo. Authors' Conclusions There is no clear benefit to LABA in preventing asthma exacerbations in children. While there is a paucity of evidence in this area, ICS should remain the controller therapy of choice; however, the addition of LABA to ICS may result in improvement in pulmonary function measures, reduce the use of rescue medications and improve quality of life measures in children with chronic asthma. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Background Asthma is a common childhood disease characterised by chronic inflammation of the airways. One treatment option is the class of medications known as the leukotriene receptor antagonists (LTRAs). The use of LTRA in combination with inhaled corticosteroid (ICS) may improve asthma control by reducing mucus secretion, inflammation and bronchoconstriction via this alternate pathway. Objectives To synthesise the evidence currently in The Cochrane Library Database Of Systematic Reviews (CDSR) related to the question, ‘In children with symptomatic but stable asthma, does treatment with a LTRA as a primary or add-on therapy to ICS improve objective measures of lung function and asthma symptom control, reduce exacerbations, and improve quality of life compared to standard care?’ Methods CDSR was searched using the term ‘asthma’ in the title for all systematic reviews examining anti-leukotriene agents vs any other pharmacological agent for the treatment of asthma. Data were extracted and entered into tables; data were synthesised using qualitative and quantitative methods. Main Results Three reviews were identified; however, only two reviews contained data in children. There was no significant difference in change in FEV1, number of missed school days, or the proportion of children requiring oral corticosteroid treatment, or proportion of children who experienced an asthma exacerbation requiring hospital admission among those randomised to LTRA vs ICS. The addition of LTRA treatment to ICS resulted in no significant difference in the change in FEV1 or morning PEFR, use of β2-agonist rescue medication, proportion of children admitted to the hospital due to an asthma exacerbation, or quality of life. Authors' Conclusions Until further evidence is available for children, LTRAs should not be substituted for ICS as monotherapy and ICS should remain the first line therapy for children with asthma. Currently, there is insufficient evidence to conclude that anti-leukotriene agents added to ICS therapy improves asthma control, steroid-sparing effect, or improved quality of life. Future research should address the gaps in children, including those as young as 2 years of age. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Background: RSV in infants with CF has significant morbidities. Objectives: To evaluate effectiveness and safety of palivizumab RSV prophylaxis in infants with CF. Methods: Data on respiratory illness and RSV hospitalizations(RIH and RSVH) were collected in infants Results: 130 infants(43 PVZ;87 UPVZ) were included. PVZ group had more infants diagnosed by newborn screen(60.5% vs. 23.0%,χ 2 =17.7,df=1,p 2 =3.7,df=1,p=0.05) than UPVZ. 49 infants had a total of 82 RIH and 6 infants had 8 RSVH. PVZ treatment did not predict number of RIH(Incidence Rate Ratio [IRR]=1.1,95%CI=0.6-1.8,p=0.8), after adjustment for CF diagnosis method and FTT, while FTT itself was a significant predictor(IRR=1.7,95%CI=1.1-2.7,p=0.03). RSVH was not predicted by PVZ treatment(IRR=0.3,95%CI=0.04-2.84,p=0.3), method of CF diagnosis(IRR=0.4,95%CI=0.04-3.32,p=0.4) nor FTT(IRR=1.5,95%CI=0.4-6.0,p=0.5). For RSVH, there were no differences between groups in days of intensive care(mean 5.0±5.7,n=2), O 2 use(mean 6.5±0.7,n=2) or total length of stay(mean 34.5±36.1,n=6,U=0.00,p=0.3). There were no serious adverse events related to PVZ. Conclusions: There were no differences in RSVH and RIH or morbidities between groups. Though sample size is one of the largest reported, power may be insufficient to detect differences. Further larger prospective studies are needed.

background The benefits of dexamethasone treatment for moderate-to-severe croup are well established. However, most children with croup have mild symptoms, and it is unknown whether they would derive the same degree of benefit from dexamethasone treatment as children with more severe disease. methods We conducted a double-blind trial at four pediatric emergency departments in which 720 children with mild croup were randomly assigned to receive one oral dose of either dexamethasone (0.6 mg per kilogram of body weight) or placebo. The children had mild croup, as defined by a score of ≤2 on the croup scoring system of Westley et al. The primary outcome was a return to a medical care provider for croup within seven days after treatment. The secondary outcome was the presence of ongoing symptoms of croup on days 1, 2, and 3 after treatment. Other outcomes included economic costs, hours of sleep lost by the child, and stress on the part of the parent in relation to the child’s illness. results Baseline clinical characteristics were similar in the two groups. Return to medical care was significantly lower in the dexamethasone group (7.3 percent vs. 15.3 percent, P

The case of Munchausen’s syndrome presenting as hemop-tysis in a 12-year-old girl is presented. The features of Munchausen's syndrome are reviewed. Munchausen’s syndrome should be included in the differential diagnosis of hemoptysis in a child, especially when accompanied by a dramatic presentation, changing symptoms and negative diagnostic investigations.

Background Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine may prevent intubation. Objectives To assess the efficacy (measured by croup scores, rate of intubation and health care utilization such as rate of hospitalization) and safety (frequency and severity of side effects) of nebulized epinephrine versus placebo in children with croup, evaluated in an emergency department (ED) or hospital setting. Search methods We searched CENTRAL 2013, Issue 6, MEDLINE (1966 to June week 3, 2013), EMBASE (1980 to July 2013), Web of Science (1974 to July 2013), CINAHL (1982 to July 2013) and Scopus (1996 to July 2013). Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: nebulized epinephrine versus placebo, racemic nebulized epinephrine versus L-epinephrine (an isomer) and nebulized epinephrine delivered by intermittent positive pressure breathing (IPPB) versus nebulized epinephrine without IPPB. Primary outcome was change in croup score post-treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects. Data collection and analysis Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodological quality assessment. One author extracted data while the second checked accuracy. We use the standard methodological procedures expected by the Cochrane Collaboration. Main results Eight studies (225 participants) were included. In general, children included in the studies were young (average age less than two years in the majority of included studies). Severity of croup was described as moderate to severe in all included studies. Six studies took place in the inpatient setting, one in the ED and one setting was not specified. Six of the eight studies were deemed to have a low risk of bias and the risk of bias was unclear in the remaining two studies. Nebulized epinephrine was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I2 statistic = 0%). This effect was not significant two and six hours post-treatment. Nebulized epinephrine was associated with significantly shorter hospital stay than placebo (one RCT, MD -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of nebulized epinephrine via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42). None of the studies sought or reported data on adverse effects. Authors' conclusions Nebulized epinephrine is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or L-epinephrine, or IPPB over simple nebulization. The authors note that data and analyses were limited by the small number of relevant studies and total number of participants and thus most outcomes contained data from very few or even single studies.

Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine (NE) may prevent intubation.To evaluate the efficacy and safety of NE in children presenting to emergency department (ED) or admitted to hospital with croup.We searched CENTRAL (The Cochrane Library 2010, Issue 4), containing the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (1966 to November Week 1, 2010), EMBASE (1980 to November 2010), Web of Science (1974 to November 2010), CINAHL (1982 to November 2010) and Scopus (1996 to November 2010).Randomized controlled trials (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: NE versus placebo, racemic NE versus L-epinephrine (an isomer), and NE delivered by intermittent positive pressure breathing (IPPB) versus NE without IPPB. Primary outcome was change in croup score post-treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects.Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodologic quality assessment. One author extracted data while the second checked accuracy. We performed standard statistical analyses.Eight studies (225 participants) were included. NE was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I(2) statistic = 0%). This effect was not significant two and six hours post-treatment. NE was associated with significantly shorter hospital stay than placebo (one RCT, mean difference -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of NE via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42).NE is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or LE, or IPPB over simple nebulization.

BACKGROUND Tracheoesophageal fistula (TEF) is a rare congenital anomaly with chronic morbidities. Aside from health care costs, the authors suspected that additional burden rests on the family due to hospitalizations, radiological and surgical procedures, and frequent outpatient visits. It was speculated that this complex care is poorly coordinated. The objective of the present study was to document utilization and coordination of health care services for children with TEF at the Alberta Children's Hospital (Calgary, Alberta). METHODS Medical records of children with TEF (primary surgical repair at Alberta Children's Hospital between April 1994 and September 1999) were reviewed for demographics, TEF type, associated anomalies, age at diagnosis and repair, health services utilization data, and radiological and surgical procedures. RESULTS Twenty-two children were identified, of whom 18 survived beyond one year. Ten of these 18 children were male. Average gestational age and birth weight were 37.4 weeks (range 32 to 42 weeks) and 2512 g (range 780 g to 3950 g), respectively. Seventy-eight per cent of children had at least one associated anomaly. Median initial hospital and intensive care unit stays were 27.5 days and 12 days, respectively. During year 1 of life, there was a median of 31 radiological examinations, five surgical procedures, 2.5 hospital admissions and five outpatient clinic visits. Coordination of procedures and outpatient visits was poor. In year 2 of life, children had fewer procedures, admissions and outpatient visits; between years 2 and 5, procedures or admissions were rare. CONCLUSIONS Children with TEF endure multiple procedures and lengthy hospital admissions in early life. There was easy access to, but minimal coordination of, subspecialist care, procedures and admissions. A dedicated multidisciplinary clinic for children with TEF should improve care.

There are striking differences between the genders with respect to the onset age and subsequent prevalence of asthma over the human lifespan. Boys appear to have a slight disadvantage in terms of pulmonary mechanics in the early years of life, which may predispose them to higher risks of wheezing and subsequent diagnosis of asthma. In early childhood, boys are more likely to be diagnosed with asthma than girls. As adolescence approaches, there is a noticeable shift, with the female population carrying a larger proportion of asthma, which is a trend that continues into adulthood. The reasons for these changes are certainly a result of a complex combination of factors, including gender-related factors, which are addressed in this chapter. Some of the evidence such as longer hospitalizations for women suggests that asthma might be more severe as well as more prevalent in women.

Changes in reproductive hormones have important influences on asthma in women. In early childhood, asthma is less common in girls (the female to male ratio is about 1: 2), but by menarche, the gender ratio is equal. Perimenstrual exacerbation(s) of asthma occurs in about 40% of women. Asthma symptoms and exacerbation(s) may increase perimenstrually with considerable reduction in expiratory airflow or change in non-specific airways hypereactivity. Oral contraceptives may attenuate these changes, especially in those women who experience more severe exacerbations with menstruation compared to those not receiving oral contraceptives. This appears to be related to suppression of the luteal phase rise in reproductive hormones caused by oral contraceptives. Case reports demonstrating a reduction in the frequency and severity of asthma exacerbation(s) during treatment with continuous gonadotropin releasing hormone antagonist analogues may also provide a clue to the mechanism(s) of perimenstrually exacerbated asthma. Leukotrienes are implicated in the pathogenesis of perimenstrually associated asthma and agents which block the effects of leukotrienes may be useful in the treatment of perimenstrually associated asthma. Further support for a relationship between reproductive hormones and asthma is derived from studies of asthma in pregnancy. Changes in asthma severity ranging from improvement to deterioration to no change may occur. Women generally experience a similar pattern from one pregnancy to the next, whatever the change. At menopause, the epidemiology of asthma changes again. The age-adjusted risk of asthma is lower in post-menopausal women who have never received hormone replacement therapy compared to pre-menopausal women or to post-menopausal women who have used hormone replacement therapy. The risk of asthma is greatest in women with the longest duration of hormone replacement therapy and those currently using conjugated estrogens. Previous exposure to an oral contraceptive agent(s) is independently associated with a small increased risk of asthma. These data suggest that female reproductive hormones play a significant role in the pathophysiology of asthma in women. The findings may have significant implications in the management of asthma in women.

Background. In an era of increasing antibiotic resistance, the prevalence of antibiotic usage and associated factors should be ascertained to optimize their use. We set out to determine the prevalence of antibiotic use in febrile children diagnosed with respiratory tract illnesses at a children's hospital emergency department; to determine how often viral studies were conducted; and to identify patient characteristics associated with antibiotic use. Methods. We conducted a retrospective study of antibiotic use in febrile children 3 months to 10 years old presenting with respiratory illnesses during two 1-month periods. Patient charts and laboratory tests were reviewed. Antibiotic use was related to diagnosis by logistic regression. Results. A total of 836 patient visits were selected. Antibiotics were prescribed for otitis media in 96% of patients, for pneumonia in 100%, for pharyngitis in 66%, for bronchiolitis in 38%, for reactive airway disease in 24% and for viral or upper respiratory tract illness in 14%. For viral illness or upper respiratory tract infection, antibiotic use was associated with a fever duration of >48 h [odds ratio (OR), 3.2; 95% confidence interval (CI) 1.7, 5.9] and having a chest radiograph performed (OR 2.1; 95% CI 1.02, 4.37). Patients with pharyngitis who had a throat swab were less likely to receive an antibiotic (OR 0.08; 95% CI 0.02, 0.4) than those who did not have a swab. In this emergency department antibiotic use for these indications decreased by 11% during the 1997 to 1998 study interval (P < 0.001). Conclusion. Antibiotics were commonly prescribed for pharyngitis, bronchiolitis and reactive airway disease, which are conditions principally caused by viruses. Addressing reasons why there is a difference between guidelines and antibiotic use in these conditions may be important.

Croup is a common childhood illness. The majority of children presenting with an acute onset of barky cough, stridor and indrawing have croup. A careful history and physical examination is necessary to confirm the diagnosis of croup, and to rule out potentially serious alternative causes of upper airway obstruction. Nebulized adrenaline is effective for the temporary relief of airway obstruction. Corticosteroids are the mainstay of treatment in children with croup of all levels of severity.