Showing papers in "Pediatric Pulmonology in 2016"

Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review

Abstract: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long-term therapeutics in PCD patients.

Respiratory effects of air pollution on children

Abstract: A substantial proportion of the global burden of disease is directly or indirectly attributable to exposure to air pollution. Exposures occurring during the periods of organogenesis and rapid lung growth during fetal development and early post-natal life are especially damaging. In this State of the Art review, we discuss air toxicants impacting on children's respiratory health, routes of exposure with an emphasis on unique pathways relevant to young children, methods of exposure assessment and their limitations and the adverse health consequences of exposures. Finally, we point out gaps in knowledge and research needs in this area. A greater understanding of the adverse health consequences of exposure to air pollution in early life is required to encourage policy makers to reduce such exposures and improve human health.

Protracted bacterial bronchitis: The last decade and the road ahead.

Abstract: Cough is the single most common reason for primary care physician visits and, when chronic, a frequent indication for specialist referrals. In children, a chronic cough (>4 weeks) is associated with increased morbidity and reduced quality of life. One common cause of childhood chronic cough is protracted bacterial bronchitis (PBB), especially in children aged <6 years. PBB is characterized by a chronic wet or productive cough without signs of an alternative cause and responds to 2 weeks of appropriate antibiotics, such as amoxicillin-clavulanate. Most children with PBB are unable to expectorate sputum. If bronchoscopy and bronchoalveolar lavage are performed, evidence of bronchitis and purulent endobronchial secretions are seen. Bronchoalveolar lavage specimens typically reveal marked neutrophil infiltration and culture large numbers of respiratory bacterial pathogens, especially Haemophilus influenzae. Although regarded as having a good prognosis, recurrences are common and if these are frequent or do not respond to antibiotic treatments of up to 4-weeks duration, the child should be investigated for other causes of chronic wet cough, such as bronchiectasis. The contribution of airway malacia and pathobiologic mechanisms of PBB remain uncertain and, other than reduced alveolar phagocytosis, evidence of systemic, or local immune deficiency is lacking. Instead, pulmonary defenses show activated innate immunity and increased gene expression of the interleukin-1β signalling pathway. Whether these changes in local inflammatory responses are cause or effect remains to be determined. It is likely that PBB and bronchiectasis are at the opposite ends of the same disease spectrum, so children with chronic wet cough require close monitoring.

Pediatric bronchiectasis: No longer an orphan disease.

Abstract: Bronchiectasis is described classically as a chronic pulmonary disorder characterized by a persistent productive cough and irreversible dilatation of one or more bronchi. However, in children unable to expectorate, cough may instead be wet and intermittent and bronchial dilatation reversible in the early stages. Although still considered an orphan disease, it is being recognized increasingly as causing significant morbidity and mortality in children and adults in both affluent and developing countries. While bronchiectasis has multiple etiologies, the final common pathway involves a complex interplay between the host, respiratory pathogens and environmental factors. These interactions lead to a vicious cycle of repeated infections, airway inflammation and tissue remodelling resulting in impaired airway clearance, destruction of structural elements within the bronchial wall causing them to become dilated and small airway obstruction. In this review, the current knowledge of the epidemiology, pathobiology, clinical features, and management of bronchiectasis in children are summarized. Recent evidence has emerged to improve our understanding of this heterogeneous disease including the role of viruses, and how antibiotics, novel drugs, antiviral agents, and vaccines might be used. Importantly, the management is no longer dependent upon extrapolating from the cystic fibrosis experience. Nevertheless, substantial information gaps remain in determining the underlying disease mechanisms that initiate and sustain the pathophysiological pathways leading to bronchiectasis. National and international collaborations, standardizing definitions of clinical and research end points, and exploring novel primary prevention strategies are needed if further progress is to be made in understanding, treating and even preventing this often life-limiting disease.

Age‐based analysis of pediatric upper airway dimensions using computed tomography imaging

Abstract: SummaryBackground Recent studies have challenged the historically accepted fact that the larynx is cone-shaped in infants and children. The present study used computed tomography (CT)-based measurements to evaluate airway dimensions. The purpose of this investigation was to determine the dimensional transition between the subglottic area and the cricoid ring in children. Methods This is a retrospective review of 220 CT scans of children aged 1 month to 10 years undergoing radiological evaluation unrelated to airways symptomatology. The CT scans were evaluated in children either sleeping naturally or sedated throughout the study period. Anteroposterior (AP) and Transverse (T) diameters were measured at the subglottic level and at the cricoid ring. Results The mean (±SD) age was 47.4 ± 33.1 months. The mean AP and transverse diameters were 9.2 ± 1.9 and 7.5 ± 1.6 mm at the subglottic area and 8.5 ± 1.7 and 8.3 ± 1.5 mm at the cricoid. AP dimension showed a decrease from the subglottis to the cricoid ring. A more rapid enlargement of the airway from the subglottis to cricoid ring is observed in the transverse dimension (P 0.7). Conclusion The narrower transverse dimension compared to the AP diameter suggests that the airway is elliptical immediately below the vocal cords. The present study demonstrates that the airway characteristics in children between the subglottic area and the cricoid change from an elliptical to a round (circular) shape. The cone-shaped airway characteristic, which has been historically proposed, was not observed. Given that subglottic transverse diameter is the smallest area dimension, one must assume this is the most likely area of resistance to the passage of an endotracheal tube rather than only the cricoid. Pediatr Pulmonol. 2016;51:267–271. © 2015 Wiley Periodicals, Inc.

Initial experience with a new biodegradable airway stent in children: Is this the stent we were waiting for?

Abstract: Objective To report our experience with a new type of biodegradable airway stent in the setting of severe tracheobronchial obstruction in children. Design and Methodology We conducted a retrospective and prospective (since June 2014) study of pediatric patients with severe airway obstruction treated with biodegradable stents in our institution between 2012 and 2015. The following data were collected: demographics, indication for stenting, bronchoscopic findings, insertion technique complications, clinical outcome, stent related complications, re-stenting, and time of follow-up. Results Thirteen custom-made polydioxanone stents were placed in four infants (mean age, 4 months) with severe tracheobronchial obstruction: tracheomalacia (two patients), bronchomalacia (1), and diffuse tracheal stenosis (1). All the stents were bronchoscopically inserted uneventfully. Immediate and maintained clinical improvement was observed in every case. No major stent related complications have occurred and only mild or moderate granulation tissue was observed during surveillance bronchoscopy. Two patients required repeated stenting as expected. All the patients are alive and in a good respiratory condition with a follow-up ranging from 5 to 40 months. Conclusions Biodegradable airway stents seem to be safe, effective, and cause fewer complications than other types of stents. They can be an alternative to the classic metallic or plastic stents for severe tracheal stenosis or malacia in small children. More experience is needed in order to establish the definite clinical criteria for their use in pediatric patients.

Multidisciplinary care of children with repaired esophageal atresia and tracheoesophageal fistula.

Abstract: OBJECTIVES Children with congenital esophageal atresia with tracheoesophageal fistula (TEF) require complex medical and surgical care, but few guidelines exist to guide the long term care of this population. The purpose of this study is to describe the findings and initial management of a comprehensive aerodigestive team in order to understand the ongoing needs of children with repaired TEF. METHODS A retrospective chart review was performed on children with TEF who were seen in the multidisciplinary Aerodigestive Clinic at Children's Hospital Colorado. Diagnostic studies were ordered based on physician discretion. RESULTS Twenty-nine children with TEF were evaluated (mean age 3.8 years) between 2010 and 2014. All children had symptoms attributed to breathing, swallowing, and digestive difficulties. Less than half of the children had seen a pulmonary or gastrointestinal specialist in the past year. Tracheomalacia was diagnosed in all children who had a bronchoscopy (23/23), and the presence of dysphagia was correlated with severe tracheomalacia. 7/25 children who had a swallow study had aspiration. 7/25 children had a diagnosis of active reflux despite current management. Four patients were diagnosed with bronchiectasis as a result of the multidisciplinary evaluation. CONCLUSION Although all children had persistent aerodigestive symptoms, over 50% had not been seen by an appropriate subspecialist in the year prior to the clinic visit. The multidisciplinary evaluation resulted in new diagnoses of bronchiectasis and active reflux, which can both lead to long-term morbidity and mortality. Children with TEF require evaluation by multiple subspecialists to manage not only current symptoms but also long term risks. Ongoing care should be guided by protocols based on known risks. Pediatr Pulmonol. 2016;51:576-581. © 2015 Wiley Periodicals, Inc.

The burden of community-managed acute respiratory infections in the first 2-years of life.

Abstract: Background: Contemporary information on acute respiratory infections (ARIs) in children is based on hospital cohorts, primary healthcare presentations, and high-risk birth cohort studies. We describe the burden and determinants of symptomatic episodes of ARIs in unselected healthy infants in the first 2-years of life. Methods: One hundred and fifty-four infants from subtropical Brisbane, Australia participated in a longitudinal, community-based birth cohort study. A daily tick-box diary captured pre-defined respiratory symptoms. Parents also completed a burden diary, recording family physician and hospital visits, and antibiotic use. Results: Participants contributed 88,032 child-days (78.2% of expected), of which 17,316 (19.7%) days were symptomatic during 1,651 ARI episodes: incidence rate 0.56 ARIs per child-month (95%CI: 0.54, 0.59). Runny nose (14,220 days; 6.0-days median duration) and dry cough (6,880 days; 4.0-days median duration) were reported most frequently. Overall, 955 burden diaries recorded 455 family physician visits (1–8 visits per ARI) and 48 hospital presentations, including six hospital admissions. Antibiotics were prescribed on 209 occasions (21.9% of ARI episodes where burden diary submitted). Increasing age, non-summer seasons, and attendance at childcare were associated with an increased risk of ARI. Conclusions: ARIs are a common cause of morbidity in the first 2-years of life, with children experiencing 13 discrete ARI episodes and almost 5-months of respiratory symptoms. Most ARIs are managed in the community by parents and family physicians. Antibiotic prescribing remains common for ARIs in young children. Secular societal changes, including greater use of childcare in early childhood, may have maintained the high ARI incidence in this age-group. Pediatr Pulmonol. 2016;51:1336–1346.

Long term continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) in children: Initiation criteria in real life

Abstract: Summary Introduction Long term noninvasive continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are increasingly used in children but limited information is available on the criteria and conditions leading to the initiation of these treatments. The aim of the study is to describe the objective overnight respiratory parameters and clinical situations that led to the initiation of CPAP/NIV in a pediatric NIV unit. Material and Methods Retrospective analysis of the data of all the children discharged on home CPAP/NIV over a 1 year period. Results Seventy-six patients were started on CPAP (n = 64) or NIV (n = 12). CPAP/NIV was initiated because of CPAP/NIV weaning failure (Acute group) in 15 patients. None of these patients had an overnight gas exchange or sleep study before CPAP/NIV initiation. In 18 patients, CPAP/NIV was initiated on abnormal nocturnal gas exchange alone (Subacute group). These patients had a median of three of the following five overnight gas exchange abnormalities: minimal pulse oximetry (SpO2) 50 mmHg, time spent with SpO2 50 mmHg ≥2% of recording time, oxygen desaturation index >1.4/hr. In the last 43 patients, CPAP/NIV was initiated after an abnormal sleep study (Chronic group) on a mean of four of the aforementioned criteria and an apnea-hypopnea index >10/hr. Conclusion In clinical practice, CPAP/NIV was initiated in an acute, subacute and chronic setting with most patients having an association of several abnormal gas exchange or sleep study parameters. Future studies should evaluate the effectiveness and benefits of CPAP/NIV according to the clinical situation and initiation criteria. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

Cardiac phenotype determines survival in Duchenne muscular dystrophy.

Abstract: SummaryObjective To identify determinants of survival by comparing cardiopulmonary function in two patient groups: prolonged survivors of Duchenne muscular dystrophy (DMD) versus DMD patients who experienced early death (ED). Methods Retrospective chart review of our DMD patients from 1999 to 2013. Prolonged Survival (PS) was defined as alive and ≥30 years old. Early death (ED) was defined as death at < 30 years old. Exclusion criteria: steroid therapy. Results Eleven patients met criteria for PS and 14 patients for ED (mean age ± SD: 34.3 ± 4.3 years vs. 21.7 ± 3.8 years, respectively; P < 0.001). Pulmonary function was better in the ED patients: all PS patients had a vital capacity of 0 ml (n = 11) versus 23% (3/13) of the ED patients (P < 0.001). Thirteen of 14 ED patients and all PS patients received assisted ventilation. Heart function was worse in the ED patients: ejection fraction (EF) was 42.2 ± 14.2% in the PS patients (n = 11) versus 29.2 ± 14.1% in the ED patients (n = 13; P = 0.035). Dilated cardiomyopathy was present in 36% (4/11) of PS patients versus 78% (11/14) of ED patients (P =0.048). Among ED patients, 57% (8/14) died from progressive cardiomyopathy. Conclusion In our study group, good heart function was a pre-condition for PS and poor heart function was the primary cause of early death. Our results suggest that, when DMD patients are treated with assisted ventilation, heart function is the main determinant of their survival. Pediatr Pulmonol. 2016;51:70–76. © 2015 Wiley Periodicals, Inc.

Lung CT imaging in patients with bronchopulmonary dysplasia: A systematic review

Abstract: SummaryBackground Bronchopulmonary dysplasia (BPD) is a common respiratory complication of preterm birth and associated with long-term respiratory sequelae. Chest computed tomography (CT) is a sensitive tool to obtain insight in structural lung abnormalities and may be a predictor for later symptoms. Objectives To give an overview of chest CT scoring methods that are used to evaluate chest CT scans of BPD patients. To review which structural lung abnormalities are described in children and adults with BPD and whether these are related to clinical outcomes. Methods An extensive literature search was conducted for relevant studies on chest CT imaging in patients born preterm with BPD. Results We retrieved 316 original papers of which 16 articles and three abstracts fulfilled our inclusion criteria. Overall, we identified nine different semi-quantitative scoring methods. Chest CT scans revealed structural abnormalities in >85% of BPD patients. These abnormalities are decreased pulmonary attenuation, opacities, bronchial wall thickening, and consolidations. Some have been found to be negatively correlated with lung function and respiratory symptoms. Conclusions None of the currently described scoring systems are appropriately validated or superior over another. Future studies are needed to generate a validated and universal chest CT quantitative scoring method for patients with BPD. Pediatr Pulmonol. 2016; 51:975–986. © 2016 Wiley Periodicals, Inc.

Therapeutic challenges posed by critical drug-drug interactions in cystic fibrosis.

Abstract: Summary This review seeks to re-introduce cystic fibrosis (CF) clinicians to the pharmacology of drug–drug interactions among medications commonly used in CF and provide a framework for understanding these interactions among medications outside the scope of this discussion. We here focus on drugs impacted by the cytochrome P-450 (CYP450) enzyme system and on interactions involving antimicrobials, psychotropic medications, and cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Particular attention is needed when prescribing rifampin, azole antifungals and the CFTR modulators, ivacaftor, and lumacaftor/ivacaftor, in combination with other medications. The complexities of these interactions provide a strong rationale for case management by pharmacists and pharmacologists as a routine part of CF care. Pediatr Pulmonol. 2016;51:S61–S70. © 2016 Wiley Periodicals, Inc.

Improving knowledge, technical skills, and confidence among pediatric health care providers in the management of chronic tracheostomy using a simulation model

Abstract: SummaryObjective The results from a recent national survey about catastrophic complications following tracheostomy revealed that the majority of events involved a loss of airway. Most of the events due to airway loss involved potentially correctable deficits in caregiver education. Training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the knowledge and confidence level of pediatric health care providers at a large tertiary care children's hospital in routine and emergency tracheostomy care and evaluated the efficacy of a comprehensive simulation-based tracheostomy educational program. Methods The prospective observational study was comprised of 33 subjects including pediatric residents, internal medicine–pediatric residents, pediatric hospitalist faculty physicians, and advanced practice registered nurses who are involved in the care of patients with tracheostomies within a tertiary-care children's hospital. The subjects completed self-assessment questionnaires and objective multiple-choice tests before and after attending a comprehensive educational course that employed patient simulation. The outcome measurements included pre- and post-course questionnaires, pre- and post-course test scores, and observational data from the simulation sessions. Results Before the education and simulation, the subjects’ comfort and confidence levels on a five-point Likert scale in performing routine tracheostomy tube care, routine tracheostomy tube change, and an emergency tracheostomy tube change were as follows (median (Q1, Q3)): 1 (1, 2), 1 (1, 2), and 1 (1, 2), respectively (n = 28). The levels of comfort and confidence after completing the course improved significantly to 4 (4, 5), 4 (4, 5), 4 (4, 5), respectively (P < 0.001) (n = 20). For the knowledge assessment, the pre-course test mean score was 0.53 ± 0.50, and the scores on the post-course test improved significantly with a mean score of 0.82 ± 0.39 (P < 0.001). During the educational intervention, specific deficiencies observed included a lack of understanding or familiarity with different types of tracheostomy tubes (e.g., cuffed versus uncuffed), physiological significance of the cuff, mechanism of action and physiological significance of the speaking valve, and the importance of the obturator in changing the tracheostomy tube. Conclusion There is a need for improved tracheostomy education among pediatric health care providers. Incorporation of patient-simulation into a tracheostomy educational program was effective in improving knowledge, confidence, and skills. Pediatr Pulmonol. 2016;51:696–704. © 2015 Wiley Periodicals, Inc.

Bronchiolitis: Analysis of 10 consecutive epidemic seasons

Abstract: Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330-1335. © 2016 Wiley Periodicals, Inc.

Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula.

Abstract: SummaryObjective To measure mean airway pressure (MAP) delivered through the RAM Cannula® when used with a ventilator in CPAP mode as a function of percent nares occlusion in a simulated nasal interface/test lung model and to compare the results to MAPs using a nasal continuous positive airway pressure (NCPAP) interface with nares fully occluded. Study Design An artificial airway model was connected to a spontaneous breathing lung model in which MAP was measured at set NCPAP levels between 4 and 8 cmH2O provided by a Drager Evita XL® ventilator and delivered through three sizes of RAM cannulae. Measurements were performed with varying leakage at the nasal interface by decreasing occlusion from 100% to 29%, half-way prong insertion, and simulated mouth leakage. Comparison measurements were made using the Drager BabyFlow® NCPAP interface with a full nasal seal. Results With simulated mouth closed, the Drager interface delivered MAPs within 0.5 cmH2O of set CPAP levels. For the RAM cannula, with 60–80% nares occlusion, overall delivered MAPs were 60 ± 17% less than set CPAP levels (P < 0.001). Further, MAP decreased progressively with decreasing percent nares occlusion. The simulated open mouth condition resulted in significantly lower MAPs to <1.7 cmH2O. The one-half prong insertion depth condition, with closed mouth, yielded MAPs approximately 35 ± 9% less than full insertion pressures (P < 0.001). Conclusions In our bench tests, the RAM interface connected to a ventilator in NCPAP mode failed to deliver set CPAP levels when applied using the manufacturer recommended 60–80% nares occlusion, even with closed mouth and full nasal prong insertion conditions. Pediatr Pulmonol. 2016;51:60–69. © 2015 Wiley Periodicals, Inc.

Validating chest MRI to detect and monitor cystic fibrosis lung disease in a pediatric cohort

Abstract: Summary Background Computed Tomography (CT) is the gold standard to assess bronchiectasis and trapped air in cystic fibrosis (CF) lung disease, but has the disadvantage of radiation exposure. Magnetic Resonance Imaging (MRI) is a radiation free alternative. Objective To validate MRI as outcome measure by: correlating MRI scores for bronchiectasis and trapped air with clinical parameters, and by comparing those MRI scores with CT scores. Methods In patients with CF (aged 5.6–17.4 years), MRI and CT were alternated annually during routine annual check-ups between July 2007 and January 2010. Twenty-three children had an MRI performed 1 year prior to CT, 34 children had a CT 1 year prior to MRI. Bronchiectasis and trapped air were scored using the CF-MRI and CF-CT scoring system. CF-MRI scores were correlated with clinical parameters: FEV1, Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms measured on the Cystic Fibrosis Questionnaire-Revised (CFQ-R), using Spearman's correlation coefficient. MRI and CT scores were compared using intra-class correlation coefficients (ICC) and Bland–Altman plots. Results Fifty-seven patients who had an MRI, CT and CFQ-R during the study period were included. CF-MRI bronchiectasis correlated with FEV1, Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory symptoms. CF-MRI trapped air only correlated with FEV1 and Pseudomonas aeruginosa. ICCs between MRI and CT bronchiectasis and trapped air were 0.41 and 0.35 respectively. MRI tended to overestimate bronchiectasis compared to CT. Conclusion The associations between CF-MRI scores and several important clinical parameters further contributes to the validation of MRI. MRI provides different information than CT. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

A multicenter study on the utility and safety of EBUS-TBNA and EUS-B-FNA in children.

Abstract: Summary Background and Aim Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound with an echobronchoscope-guided fine needle aspiration (EUS-B-FNA) are useful modalities in the evaluation of mediastinal lymphadenopathy in adults; however, there is sparse data in children. The aim of this multicenter study is to describe the efficacy and safety of EBUS-TBNA and EUS-B-FNA in children with mediastinal lymphadenopathy of undefined etiology. Methods Retrospective analysis of consecutive pediatric (<18 years) subjects who underwent EBUS-TBNA or EUS-B-FNA for the evaluation of mediastinal lymphadenopathy. The demographic characteristics, indications, procedural details, pathological, cytological and microbiological diagnosis, diagnostic yield, and complications are presented. Results Of the 3,424 EBUS/EUS-B-FNA procedures, 67 (1.9%) were performed in the pediatric (3–17 years) population. Of these, 19 (28.4%) were performed in children ≤12 years of age. Overall, EBUS-TBNA and EUS-B-FNA were performed in 53 and 12 subjects, respectively. In two subjects, no significant lymph node was seen on EBUS. The procedure was performed under moderate sedation in spontaneously breathing subjects in 54 (80.6%) instances. An adequate sample was obtained in 60 (92.3%) subjects while a diagnostic sample was obtained in 37 (56.9%) of the 65 subjects. The diagnostic yield was not significantly different (P = 0.59) between EBUS-TBNA (58.5%) and EUS-B-FNA (50%). The sensitivity of EBUS-TBNA/EUS-B-FNA was 79.1% and led to a change in diagnosis in 28 (41.8%) subjects. Complications, all minor were encountered in six (8.9%) subjects. Conclusions EBUS-TBNA and EUS-B-FNA are safe techniques with a good diagnostic yield in the evaluation of children with mediastinal lymphadenopathy. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: Systematic review with meta-analysis.

Abstract: SummaryRationale Systemic corticosteroids (SCS) are used for treat preschoolers with acute asthma or wheezing exacerbations, with conflicting results. Objective To evaluate the effectiveness of oral corticosteroids (OCS) compared to placebo in preschoolers presenting with acute asthma/wheezing exacerbations. Methods Five electronic databases were searched for all placebo-controlled, randomized clinical trials of OCS in children <6 years of age presenting with recurrent wheezing/asthma exacerbations of any severity. Primary outcomes were hospitalizations, unscheduled emergency department (ED) visits in following month, need of additional OCS courses, and length of stay (ED or hospital). Results Eleven studies met inclusion criteria (n = 1,733); four were conducted on an outpatient basis, five in inpatients, and two in the ED. Significant heterogeneity was found when pooling all studies, and thus analysis was stratified by trial setting. Among the outpatient studies, children who received OCS had a higher hospitalization rate (RR: 2.15 [95%CI = 1.08–4.29], I2 = 0%) compared to those to received placebo. Among the ED studies, children who received OCS had a lower risk of hospitalization (RR: 0.58 [0.37–0.92], I2 = 0%). Among the inpatient studies, children who received OCS needed fewer additional OCS courses than those on placebo (RR: 0.57 [0.40–0.81], I2 = 0%). Conclusions Treatment with OCS in the ED or hospital may be beneficial in toddlers and preschoolers with frequent asthma/wheezing exacerbations. However, more studies are needed before OCS can be broadly recommended for this age group. Future trials should be carefully designed to avoid bias and according to our findings regarding administration setting. Pediatr Pulmonol. 2016;51:868–876. © 2016 Wiley Periodicals, Inc.

Early detection and sensitive monitoring of CF lung disease: Prospects of improved and safer imaging.

Abstract: Recent imaging studies using chest computed tomography (CT) in presymptomatic infants and young children with cystic fibrosis (CF) diagnosed by newborn screening presented compelling evidence of early onset and progression of structural lung damage in CF. These data argue persuasively that non-invasive outcome measures for early detection and sensitive monitoring of lung disease applicable in the clinical setting will be instrumental for further improvement of clinical care and the development of early intervention therapies that have the potential to prevent irreversible lung damage. In this context, the use of CT imaging for early detection and long-term monitoring has the disadvantage of the risk to induce malignancies due to cumulating ionizing radiation exposure. More recently, magnetic resonance imaging (MRI) has emerged as an alternative radiation-free imaging technique for quantitative assessment of CF lung disease. In addition to structural lung damage, chest MRI enables non-invasive assessment of abnormalities in lung perfusion and ventilation characteristically associated with mucus plugging in CF lung disease. Here, we review recent developments and the prospects of MRI for improved and safer imaging with a focus on recent studies that support its utility as a sensitive non-invasive outcome measure of early lung disease in young children with CF. Pediatr Pulmonol. 2016;51:S49-S60. © 2016 Wiley Periodicals, Inc.

Infection and inflammation in induced sputum from preschool children with chronic airways diseases.

Abstract: Summary Background: We hypothesized airway inflammation can be detected non-invasively by induced sputum (IS) or peripheral blood eosinophilia, and IS can detect bacterial and viral infection in preschool children with airway disease, with results comparable to broncho-alveolar lavage (BAL). Methods: Preschool children with cystic fibrosis, recurrent wheeze, or wet cough underwent IS with nebulized hypertonic saline, chest physiotherapy, and oropharyngeal suction. Samples were analyzed for inflammation by cytology and bacterial culture, viral detection by PCR. Results were compared to BAL and blood in a sub-group undergoing clinically indicated bronchoscopy. Results: 64 children (median age 33 [7–76] months) underwent IS without adverse events. IS was obtained from 61/64. Twenty out of sixty-four underwent BAL and IS, no IS was obtained in 2/23. Thirteen out of twenty-one (62%) had matching bacteria and viruses, 4/21 had positive BAL bacterial growth with negative IS, and 3/21 had negative BAL growth with positive IS. 67% of sputum samples were processed for cytology, 46% had <80% squamous cells; the proportion of squamous cells reduced with increasing age (r = −0.55, P < 0.01). IS was significantly more neutrophilic and less eosinophilic than BAL; 2/21 IS samples contained eosinophils compared to 17/23 BAL. There was a positive correlation between blood and BAL eosinophilia (r = 0.75, P < 0.01). Conclusion: IS from preschool children can be used to assess infection. BAL and IS culture concurred in approximately two-thirds. However, inflammation was measureable in only one-third of IS samples and the cell differential was predominantly neutrophilic compared to BAL. Blood eosinophils may provide a better reflection of lower airway eosinophilia in this age group. Pediatr Pulmonol. 2016;51:778–786. © 2015 WileyPeriodicals, Inc.

Genetic Medicines for CF: Hype versus Reality

Abstract: Since identification of the CFTR gene over 25 years ago, gene therapy for cystic fibrosis (CF) has been actively developed. More recently gene therapy has been joined by other forms of "genetic medicines" including mRNA delivery, as well as genome editing and mRNA repair-based strategies. Proof-of-concept that gene therapy can stabilize the progression of CF lung disease has recently been established in a Phase IIb trial. An early phase study to assess the safety and explore efficacy of CFTR mRNA repair is ongoing, while mRNA delivery and genome editing-based strategies are currently at the pre-clinical phase of development. This review has been written jointly by some of those involved in the various CF "genetic medicine" fields and will summarize the current state-of-the-art, as well as discuss future developments. Where applicable, it highlights common problems faced by each of the strategies, and also tries to highlight where a specific strategy may have an advantage on the pathway to clinical translation. We hope that this review will contribute to the ongoing discussion about the hype versus reality of genetic medicine-based treatment approaches in CF. Pediatr Pulmonol. 2016;51:S5-S17. © 2016 Wiley Periodicals, Inc.

Respiratory function and symptoms in young preterm children in the contemporary era.

Abstract: Summary Objective To determine the relationships between respiratory symptoms, lung function, and neonatal events in young preterm children. Methods Preterm children (<32 w gestation), classified as bronchopulmonary dysplasia (BPD) or non-BPD, and healthy term controls were studied. Lung function was measured by forced oscillation technique (respiratory resistance [Rrs] and reactance [Xrs]) and spirometry. Respiratory symptom questionnaires were administered. Results One hundred and fifty children (74 BPD, 44 non-BPD, 32 controls) 4–8 years were studied. Lung function (median Z-score [10,90th centile]) was significantly impaired in preterm children compared to controls for FVC (0.00 [−1.18, 1.76], 0.69 [−0.17,1.86]), FEV1 (−0.44 [−1.94, 1.11], 0.49 [−0.83, 2.51]), Xrs (−1.26 [−3.31, 0.11], −0.11 [−0.97, 0.73]), and Rrs (0.55 [−0.48, 1.82], 0.28 [−0.99, 0.96]). Only Xrs differed between the BPD and non-BPD (−1.51 [−3.59, −0.41], −0.89 [−2.64, 0.52]). The prevalence of recent respiratory symptoms (range: 32–36%) did not differ between BPD and non-BPD children. Supplemental O2 in hospital was positively associated with worsening Xrs and FEV1. Conclusion Preterm children have worse lung function than healthy controls. Only respiratory reactance differentiated between preterm children with and without BPD and was influenced by days of O2 in hospital. Pediatr Pulmonol. 2016; 9999:1–9. © 2016 Wiley Periodicals, Inc.

Mid-childhood lung function in a cohort of children with "new bronchopulmonary dysplasia".

Abstract: SummaryObjective Recent advances in perinatal care and neonatal respiratory therapy have led to a new phenotype of bronchopulmonary dysplasia (“new BPD”). The long-term respiratory outcome of this new form of BPD has yet to be adequately described. Aim of this study was to provide longitudinal data on lung function of an unselected cohort of children born extremely premature (EP) with an extremely low birth weight in the post-surfactant era. Study Design Respiratory function was assessed twice (at 8 and 12 years) in 48 children born at a gestational age <28 weeks with a birth weight <1,000 g. Twenty-eight of them had BPD (oxygen-dependency at 36 weeks postmenstrual age) (EP-BPD), and 20 not (EP non-BPD). Twenty-seven children born at term served as control group. Results The EP-BPD group had significantly lower spirometric values (given as z-scores) than controls, especially in parameters indicating airflow obstruction (8 ys: zFEV1:−1.3 ± 1 vs. 0.5 ± 0.8; 12 ys:−1.6 ± 1 vs. 0.5 ± 0.8, P < 0.001). Despite their better spirometric profile, EP-non-BPD children also had significantly lower parameters than controls (8ys: zFEV1:−0.5 ± 0.8; 12 ys:−0.5 ± 0.9, P < 0.001). During the 4-year follow-up, EP-non-BPD and controls had stable mean z-scores, but EP-BPD had a significant decline in mean zFEV1 (from −1.3 ± 1 to −1.6 ± 1, P = 0.03), zFEV1/FVC (from −0.4 ± 1 to −1.1 ± 1, P = 0.008), and zFEF 25–75% (from −1.2 ± 1 to −1.8 ± 1, P = 0.03). Conclusion EP children born in the post-surfactant era showed a significant airflow limitation, particularly pronounced in BPD subjects who in addition, presented an abnormal airway growth trajectory with a decline in lung function between the ages of 8 and 12 years. Pediatr Pulmonol. 2016;51:1057–1064. © 2016 Wiley Periodicals, Inc.

Oxygen weaning after hospital discharge in children with bronchopulmonary dysplasia.

Abstract: SummaryBackground In the United States, approximately 12,000 preterm infants are diagnosed with bronchopulmonary dysplasia (BPD) and many of these infants require supplemental oxygen after initial hospital discharge. In children with BPD we sought to identify factors associated with supplemental oxygen use after initial hospital discharge, factors associated with duration of supplemental oxygen use, and methods used to wean off supplemental oxygen in the home environment. Methods All subjects (n = 420) with the diagnosis of BPD were recruited from a single center Bronchopulmonary Dysplasia Clinic between 2008 and 2013. Subject information was obtained from patient history records, patient demographics, and caregiver questionnaires. Results Younger gestational age and having a Nissen fundoplication were associated with home supplemental oxygen use in subjects with BPD. Of the 154 subjects who received supplemental oxygen at home, 38% received flows ≤1/8 LPM, 30% received flows >1/8 LPM and ≤1/4 LPM, 21% received flows >1/4 LPM and ≤1/2 LPM, and 11% received flows >1/2 LPM. Among subjects receiving ≤1/8 LPM of oxygen, the median age of weaning off oxygen was 10.1 months, but increased depending on level of oxygen flow at initial outpatient visit. Of the 137 subjects weaned off of oxygen during the study period, weaning was not supervised by a physician in 32.1% of subjects. Conclusion Home supplemental oxygen use is common in infants diagnosed with BPD. In this study, the median age of weaning off supplemental oxygen was 10.1 months after initial hospital discharge. Unsupervised weaning of supplemental oxygen occurred in 32.1% of subjects with BPD. Pediatr Pulmonol. 2016;51:1206–1211. © 2016 Wiley Periodicals, Inc.

Recurrent diaphragmatic hernia: Modifiable and non-modifiable risk factors.

Abstract: SummaryRationale The risk of recurrence of Congenital Diaphragmatic Hernia (CDH) in an era of thoracoscopic surgery is unclear. Objectives (1) estimate the incidence and (2) evaluate the perioperative factors associated with the symptomatic recurrence of CDH. Methods Medical records of CDH infants operated on in the neonatal period at a single-tertiary hospital between January 2000 and January 2013 were retrospectively reviewed. Results Of 119 infants with CDH, 34 (28.6%) were excluded: 17 (14.3%) died without recurrence and 17 (14.3%) presented beyond neonatal period or were followed elsewhere. Of 85 survivors, 71 infants had an open repair and 14 had a thoracoscopic repair. Eleven of 85 survivors (13%) developed a recurrence on average 19.8 weeks (range 15–34) after the initial repair. Of 11 recurrences, 6 had an initial thoracoscopic repair and 5 had an open repair (6/14 [43%] vs. 5/71 [7%]; P = 0.002). Two children had multiple recurrences. Statistically significant associations were found between recurrence and the presence of persistent pulmonary hypertension (PPHTN) (P = 0.006), severe PPHTN (P = 0.002), inhaled nitric oxide, or sildenafil use for treatment of PPHTN (P = 0.002), need for perioperative high frequency oscillatory ventilation (HFOV) (P = 0.0006), length of hospital stay (LOS) (P = 0.02), duration of ventilation (P = 0.016), and need for home oxygen (P = 0.003). In multivariate regression analysis both the closure type and home oxygen requirement were statistically significant, independent factors predicting a recurrence (P = 0.04 and 0.02, respectively) but the type of surgery (thoracoscopic vs. open) only approached significance (P = 0.052). The recurrence rate for the seven surgeons who performed at least 5 repairs ranged from 7% to 40%. Conclusions A high survival rate of 85% with a 13% incidence of symptomatic CDH recurrence was demonstrated. Potentially, improved selection of cases for thoracoscopic repair and concentrating the thoracoscopic technique amongst a dedicated team of experienced thoracoscopic surgeons may reduce the rate of recurrence of CDH. Pediatr Pulmonol. 2016;51:394–401. © 2015 Wiley Periodicals, Inc.

Predictors of asthma following severe respiratory syncytial virus (RSV) bronchiolitis in early childhood

Abstract: Summary Background We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared. Methods This longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria. Results Prevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use. Conclusion Among children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

Neonatal hyperoxia increases airway reactivity and inflammation in adult mice

Abstract: Summary Background Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. Methods Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. Results Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP-1, IL-12, INF-γ) and at 15 weeks (LTB4, VEGF); Lipoxin-A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. Conclusions Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

Removal of foreign bodies in children's airways using flexible bronchoscopic CO2 cryotherapy.

Abstract: Summary Background The present retrospective study investigated the safety and efficacy of removing foreign bodies from children's airways using flexible bronchoscopic CO2 cryotherapy instead of traditional foreign body aspiration. Methods Between October 2012 and June 2014 in the Shanghai Children's Medical Center, we performed flexible bronchoscopic CO2 cryotherapy to remove foreign bodies from the airways of 12 children who ranged in age from 10 to 40 months and analyzed outcomes and complications. Results Using cryotherapy, we successfully and without complications removed the foreign bodies in eight of 12 children. In two cases, the foreign bodies were removed successfully, but cryotherapy partially damaged the airway mucosa, which caused partial airway obstruction because of the newly developed granulation tissue. We incompletely removed the foreign body in one case and failed to remove the foreign body in another case. No serious adverse reactions or complications were observed after the treatments. Conclusion Removal of foreign bodies from children's airways using flexible bronchoscopic CO2 cryotherapy may be a safe, easy, and effective method. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

Longitudinal assessment of lung function in children with sickle cell disease.

Abstract: Summary Objectives To prospectively assess longitudinal lung function in children with sickle cell disease (SCD). Working hypothesis Lung function in SCD children deteriorates with increasing age and the decline is more marked in younger children who have recently suffered ACS episodes. Study design Two prospective longitudinal studies. Patient-subject selection Two cohorts of SCD children and age and ethnic matched controls were recruited. Cohort One (47 SCD and 26 controls) had a median age of 8.8 years and follow up of 2 years and Cohort Two (45 SCD and 26 controls) a median age of 10.2 years and follow up of 10 years. Methodology Forced expiratory volume in one second (FEV1), vital capacity (VC), forced expiratory flow between 25% and 75% of VC (FEF 25–75), total lung capacity (TLC) and residual volume (RV) were measured on two occasions. Results In both groups of SCD children, lung function declined significantly, but in neither control group. ACS episodes were more frequent during the follow up period in Cohort One than Cohort Two (P < 0.0001). The rate of decline was greater in Cohort One than Cohort Two for FEV1 (P = 0.008), VC (P = 0.001), FEF25–75 (P = 0.030), TLC (P = 0.004), and RV (P = 0.043). In Cohort Two restrictive abnormalities were more common at follow up (P = 0.006). Conclusions Lung function deteriorated with increasing age in SCD children and the rate of decline was greater in younger children in whom ACS episodes were more common. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

A randomized trial of nebulized 3% hypertonic saline with salbutamol in the treatment of acute bronchiolitis in hospitalized infants

Abstract: Summary Objective Acute bronchiolitis is a common disorder of infants that often results in hospitalization. Apart from supportive care, no therapy has been shown to influence the course of the disease, except for a possible effect of nebulized hypertonic saline (HS). To determine whether this does have beneficial effects on length of stay in hospital or on severity scores, we undertook a double-blind, randomized, controlled trial in a pediatric department of a Portuguese hospital. Methods Previously healthy infants, younger than 12 months, hospitalized with mild-to-moderate acute viral bronchiolitis were randomized to receive either nebulized 3% (hypertonic, HS) or 0.9% (normal, NS) saline during their entire hospital stay. Primary endpoints were: length of hospital stay and severity scores on each day of hospitalization. Need for supplemental oxygen, further add-on medications and adverse effects were also analyzed. Results Sixty-eight patients completed the study (HS: 33; NS: 35). The median length of hospital stay did not differ between groups: HS: 5.6 ± 2.3 days; NS: 5.4 ± 2.1 days (P = 0.747). We found no difference between groups in severity scores from day 1 to day 4. There were no differences in need for supplemental oxygen or add-on medications. Patients in HS group had significantly more cough (46% vs. 20%, P = 0.025) and rhinorrhoe (58% vs. 31%, P = 0.30). Conclusion This study does not support the use of nebulized HS over NS in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.