Pediatric Pulmonology

Respiratory distress syndrome is the most common respiratory disorder in preterm infants. Over the last decade, because of improvements in neonatal care and increased use of antenatal steroids and surfactant replacement therapy, mortality from respiratory distress syndrome has dropped substantially. However, respiratory morbidity, primarily bronchopulmonary dysplasia, remains unacceptably high. The management of respiratory distress syndrome in preterm infants is based on various modalities of respiratory support and the application of fundamental principles of neonatal care. To obtain best results, a multidisciplinary approach is crucial. This review discusses surfactant replacement therapy and some of the current strategies in ventilatory management of preterm infants with respiratory distress syndrome. Key words: pediatric, respiratory, pulmonary, respiratory distress syndrome, RDS, surfactant replacement therapy, preterm newborn, bronchopulmonary dysplasia. [Respir Care 2003;48(3):279 -286. © 2003 Daedalus Enterprises] ground-glass appearance of the lung fields, with hypoin-Ricardo J Rodriguez MD is affiliated with the

To assess the potential role of multiple bronchoalveolar lavages (BALs) in the treatment of children with lipoid pneumonia (LP). This prospective study included 10 children (7 female, 3 male) with LP secondary to mineral oil aspiration. The age ranged from 3 months to 7 years and 1-60 days history of mineral oil intake, with a 6 months clinic follow-up. High-resolution computer tomography (CT) was performed 1-7 days prior to treatment and 2-20 days after the last therapeutic BAL, and reviewed by two experienced chest radiologists. Oxygen saturation was measured with digital oximetry. Therapeutic BAL was performed weekly until BAL fluid was nearly transparent and the cell count returned to normal range values. In all children, the initial CT scans showed multifocal bilateral consolidation involving mainly the dorsal and central regions. The areas of consolidation had foci of decreased attenuation in eight patients. Following a total of 4-10 therapeutic BALs, the CT scans returned to normal in 3 patients, improved considerably in 5, and showed only slight improvement in 2. Oxygen saturation increased from 88.8 +/- 3.4% at presentation to 96.2 +/- 0.8% after treatment (P < 0.0001). Multiple lavages reduced (P < 0.003) numbers of lipid-laden macrophages and restored BAL cellularity to normal range values. Multiple therapeutic BAL of children with LP results in significant improvement of CT findings, oxygen saturation, restoration of BAL fluid cellularity and clinical recover without any evidence of respiratory distress at the end of treatment and 6 months after the last BAL.

Background: Pneumonia is a leading cause of death in children of low-resource settings. Barriers to care include an early and accurate diagnosis. Lung ultrasound is a novel tool for the identification of pediatric pneumonia; however, there is currently no standardized approach to train in image acquisition and interpretation of findings in epidemiological studies. We developed a training program for physicians with limited ultrasound experience on how to use ultrasound for the diagnosis of pediatric pneumonia and how to standardize image interpretation using a panel of readers. Methods: Twenty-five physicians participating in the training program conducted lung ultrasounds in all children with suspected pneumonia, aged 3 to 35 months, presenting to three subdistrict hospitals in Sylhet, Bangladesh, between June 2015 and September 2017. Results: A total of 9051 pediatric lung ultrasound assessments were conducted through 27 months of data collection. Study physicians underwent training and all were successfully standardized, achieving 91% agreement and maintained a sensitivity and specificity of 88% and 92%, respectively, when their diagnosis was compared with experts. Overall kappa between two readers was high (0.86, 95% confidence interval [CI], 0.84-0.87), and remained high when a third expert reader was included (0.80, 95% CI, 0.79-0.81). Agreement and kappa statistics were similarly high when stratified by age, sex, presence of danger signs, or hypoxemia. Conclusions: Lung ultrasound is a novel tool for the diagnosis of pediatric pneumonia with evidence supporting its validity and feasibility of implementation. Here we introduced a training program that resulted in a high level of inter-sonographer agreement.

lntrapulmonary percussive ventilation (IPV) is a novel form of chest physiotherapy delivered by a percussive pneumatic device (IPV, Percussionaire, Sand Point, ID). There are few published reports about the use of IPV for diseases other than cystic fibrosis. We report our experience with three pediatric patients and one adult patient with persistent pulmonary consolidation refractory to conventional therapies. Three of the four patients had neurornuscular disease; one patient had segmental atelectasis due to aspiration. Three of the four patients showed clinical and radiographic improvement within 48 hours of starting IPV. The fourth patient experienced brief episodes of third-degree atrioventricular block, hypoxemia, and bradycardia during two IPV treatments. IPV was safely restarted and he slowly improved. We conclude that while IPV requires further clinical evaluation, it appears to be a safe and effective therapy for selected patients. However, close observation is essential during and after IPV treatments, especially in patients who have difficulty mobilizing or expectorating sputum. Pediatr Pulmonol.

Cystic fibrosis (CF) is a complex, chronic, multisystem disease for which there is currently no cure. Nonetheless, advances in management have led to dramatic improvements in patient survival. With this development, new issues have arisen for CF patients and their care providers, including an increased symptom burden and increased frequency of comorbidities as patients reach older ages, leading to the need for a highly complicated and timeconsuming regimen of treatments. Such high symptom and treatment burden often leads to non-adherence and low levels of competence with administration of therapy, both of which may have detrimental impacts on CF outcomes. Optimal management is also hindered by other patient-related factors, including inadequacies in disease education which may lead to issues with self-management. This is particularly important during the transition from parent-directed therapy to independent self-management that occurs during adolescence and early adulthood. Clinicians are also faced with a considerable challenge when selecting interventions for individual patients; although the paradigm of aggressive care necessitates a wide range of therapies, there is a limited evidence base with which to compare available therapeutic regimens. Novel pharmacological agents are being developed to target the underlying cause of CF, while non-pharmacological interventions aim to improve competence and maximize adherence and health outcomes. Comparative effectiveness research is needed to simplify management and facilitate the implementation of appropriate treatment strategies. Pediatr Pulmonol.

Background Asthma prevalence in African children is high. Factors driving the prevalence or disease severity are poorly understood. This study aims to investigate environmental factors associated with asthma and severity in African children. Methods Population based cross-sectional study of children aged 13-14 years from 10 African centers who participated in ISAAC III. Self-reported environmental exposures included engaging in physical exercise, television watching, various biomass and ETS exposure, consumption of paracetamol, large family sizes and having pets in the home. Univariable and multivariable analyses were done adjusting for center variations. Prevalences, odds ratio and 95% confidence intervals (CI) were calculated. Results There were 258 267 children recruited among the 13-14-year-old participants. Of these, 28,391 respondents from 232 schools completed both the written questionnaire (WQ) and environmental questionnaire (EQ). The prevalence of asthma and severe asthma ...

Measurement of esophageal pressure, as a reflection of pleural pressure, is essential for assessment of dynamic lung mechanics in neonates and infants. Conventionally, an esophageal balloon or a fluid-filled catheter is used, but considerable skill is required to obtain accurate results. Both devices have problems, and failure to achieve valid occlusion tests have been reported, particularly in small infants with lung disease. Recently, a flexible #3 French gauge (FG) microtransducer cathether (MTCB, Drager Netherlands) has become available for medical monitoring. We have assessed the accuracy and feasibility of using this device for measuring lung mechanics in 51 spontaneously breathing infants and small children aged 1 day to 24 months (weight 1.35 to 12.0 kg), 9 of whom were healthy neonates, the remainder suffering from a variety of cardio-respiratory diseases, and in 18 sick ventilated infants (weight 0.6 to 4.0 kg). Positioning of the catheter was well tolerated by all infants. The ratio of esophageal to airway opening pressure changes (AP,:APao) ranged from 0.94 to 1.09 [mean (SD) 1.01 3 (0.03)]

Background: Enhancement of mucociliary clearance by pulmonary rehabilitation (PR) is advocated in primary ciliary dyskinesia (PCD). Our primary aim was to compare the efficacy and safety of postural drainage, percussion and vibration [conventional PR (CPR)], and high frequency chest wall oscillation (HFCWO) by studying change in pulmonary function. Our secondary aim was to evaluate patient preferences regarding the two methods. Methods: This was a controlled randomized crossover study. PCD patients between the ages of 7 and 18 years were assigned to two groups, first group performed airway clearance with CPR at hospital for 5 days and after a 2-day washout period HFCWO was applied to the same group at home. HFCWO was applied first to the other group and then these patients were hospitalized for CPR. The primary outcome measure of the study was pulmonary function test (PFT). The secondary outcomes were pulse arterial oxygen saturation (SpO 2 ) and the perceived efficiency and comfort level. Results: PFT values of patients increased significantly after both PR methods (before/after): CPR: FVC: 77.0 AE 14.1/81.8 AE 13.0 (P ¼ 0.002); FEV 1 : 72.9 AE 14.8/78.7 AE 13.5 (P ¼ 0.001); PEF: 73.8 AE 14.5/82.5 AE 14.5 (P ¼ 0.001); FEF 25-75 : 68.6 AE 27.6/74.9 AE 29.3 (P ¼ 0.007). HFCWO: FVC: 75.1 AE 15.3/80.3 AE 13.9 (P ¼ 0.002); FEV 1 : 71.4 AE 16/77.4 AE 14.6 (P ¼ 0.001); PEF: 70.9 AE 18.0/78.3 AE 17.7 (P ¼ 0.002); FEF 25-75 : 70.5 AE 23.4/76.4 AE 25.6 (P ¼ 0.006). There were no significant differences in % predicted FVC, FEV 1 , PEF, and FEF 25-75 increased values with CPR and HFCWO. HFCWO was found more comfortable (P ¼ 0.04). Two PR methods were found efficient and no desaturation occurred during PR. Conclusions: PFTs were significantly increased after both PR methods. There were no differences in PFTs and SpO 2 between the CPR and HFCWO groups. Both PR methods were found efficient. HFCWO was found more comfortable. HFCWO may be an option in patients with chronic pulmonary disease and low adherence to PR. Pediatr Pulmonol.

Background: Previous research suggests that physical activity programs may improve fitness and reduce symptoms in children with asthma, but few studies have included severe asthmatics and focused on safety and parental satisfaction with the programs. Objective: To examine safety, parental satisfaction, and pre-to post-intervention changes in symptoms and quality of life (QOL) in a pilot study of the impact of vigorous physical activity (swimming) and moderate-intensity activity (golf) on inner-city children with asthma. Design/Methods: Children with asthma (7-14 years old) residing in Milwaukee's highest asthma prevalence zip codes were randomized to a 9-week swimming or golf program. Pre-and post-intervention data were obtained on safety, parental satisfaction, asthma symptoms, quality of life, and urgent asthma physician visits. Results: Twenty-eight children in the swimming group and 17 in the golf group completed the program. Combined group analysis (N ¼ 45) revealed that only six symptom exacerbations occurred during 1,125 person-sessions of swimming and golf (all resolved with bronchodilator therapy), 92% of parents were very or extremely satisfied with the program, and post-exercise decreases were observed in asthma symptom severity scores (9.3-7.3, P < 0.001), improved parental QOL (4.9-5.4, P < 0.001), and reduced urgent physician visits for asthma (1.3-0.2 visits per person, P ¼ 0.04). The study lacked sufficient power to perform intergroup comparisons. Conclusions: Findings from this pilot study indicate that vigorous (swimming) and moderate-intensity (golf) physical activity programs are well-tolerated, safe, and achieve high parental satisfaction. Participants and parents reported reduced childhood asthma symptoms and physician office visits and improved parental QOL. These findings suggest a potentially beneficial role for moderate to vigorous physical activity in childhood asthma.

Objective: Both healthy preterm infants and those with bronchopulmonary dysplasia (BPD) have poor lung function during childhood and adolescence, although there is no evidence whether prematurity alone explains the reduction in lung function found in BPD infants. Our study seeks to know if lung function, measured in infancy by means of rapid thoracic compression with raised volume technique, is different between preterm infants with and without BPD. Methods: Lung function was measured in 43 preterm infants with BPD and in 32 preterm infants without BPD at a chronological age range of 2-28 months. Forced vital capacity (FVC), forced expiratory volume at 0.5 sec, and forced expiratory flows at 50, 75, 85%, and 25-75% of FVC were obtained from maximal expiratory volume curves by means of rapid thoracic compression with raised volume technique. Maximal flow at functional residual capacity was measured using rapid thoracic compression at tidal volume. Multiple regression analysis and generalized least squares (GLS) random-effects regression model were used to control for variables such as gender, weeks of gestation, age, birth weight, and tobacco smoke exposure. A sub-analysis was performed in infants born at 28þ weeks of gestation. Results: BPD was associated to significantly lower flows (regression coefficients: À0.51, À0.54, À57, À0.53, and À0.82, respectively for FEF 50 , FEF 75 , FEF 85 , FEF 25-75). This association was driven by males and maintained in the subgroup of infants born at 28þ weeks of gestation. Conclusion: BPD is associated with an additional decrease of lung function during the first 2 years of life in infants born preterm. Pediatr Pulmonol.

Introduction: Hypoxemia is a life-threatening condition and is commonly seen in children with severe pneumonia. A government-led, NGO-supported, multifaceted oxygen improvement program was implemented to increase access to oxygen therapy in 29 hospitals in Kaduna, Kano, and Niger states. The program installed pulse oximeters and oxygen concentrators, trained health care workers, and biomedical engineers (BMEs), and provided regular feedback to health care staff through quality improvement teams. Objective: The aim of this study is to evaluate whether the program increased screening for hypoxemia with pulse oximetry and prescription of oxygen for patients with hypoxemia. Methodology: The study is an uncontrolled before-after interventional study implemented at the hospital level. Medical charts of patients under 5 admitted for pneumonia between January 2017 and August 2018 were reviewed and information on patient care was extracted using a standardized form. The preintervention period of this study was defined as 1 January to 31 October 2017 and the postintervention period as 1 February to 31 August 2018. The primary outcomes of the study were whether blood-oxygen saturation measurements (SpO 2) were documented and whether children with hypoxemia were prescribed oxygen. Results: A total of 3418 patient charts were reviewed (1601 during the preintervention period and 1817 during the postintervention period). There was a significant increase in the proportion of patients with SpO 2 measurements after the interventions were conducted (adjusted odds ratio [aOR] 5.0; 4.3-5.7, P < .001). Before the interventions, only 13.7% (95% confidence interval [CI]: 12.2-15.3) of patients had SpO 2 measurements and after the interventions, 82.4% (95% CI: 80.7-84.1) had SpO 2 measurements. Oxygen administration for patients with clinical signs of hypoxemia also increased significantly (aOR 5.0; 4.2-5.9, P < .001)-from 22.8% (95% CI: 18.8-27.2) to 77.9% (95% CI: 73.9-81.5). Conclusion: Increasing pulse oximetry and oxygen therapy access and utilization in a low-resourced environment is achievable through a multifaceted program focused on strengthening government-owned systems.

Objectives: Kawasaki disease (KD) is a multisystemic vasculitis with predominant mucocutaneous manifestations. Pulmonary involvement in KD is distinctly uncommon and is not commonly recognized. We describe our experience of managing children with KD wherein the initial presentation was predominantly pulmonary. Methods: Six hundred and two children have been diagnosed with KD during the

Wheezing illnesses are characterized by phenotypic variability, which changes with age, but few studies report on a wide age range of children. We studied how prevalence, severity, and triggers of wheeze vary throughout childhood. We analyzed data from a large population-based cohort of children from Leicestershire, UK, who were followed from infancy through late adolescence using postal questionnaires. We used generalized estimating equations to describe age-related changes in prevalence of any wheeze: episodic viral and multiple trigger wheeze; wheeze triggered by exercise, aeroallergens, food/drinks, laughing/crying; and of severe wheeze (frequent attacks, shortness of breath, sleep disturbance, disturbance of daily activities) from age 1-18 years. We analyzed this in the entire cohort (absolute prevalence) and separately among children with wheeze (relative prevalence). This study included 7670 children. Current wheeze was most common in 1-year-olds (36%) and then decreased in p...

Objective: Several options are currently available in neonatal mechanical ventilation: complete breathing synchronization (patient triggered ventilation, synchronized intermittent positive pressure ventilation-SIPPV); positive pressure flow-cycled ventilation (pressure support ventilation, PSV); and volume targeted positive pressure ventilation (volume guarantee, VG). The software algorithm for the guarantee volume attempts to deliver a tidal volume (Vt) as close as possible to what has been selected by the clinician as the target volume. Main objectives of the present study were to compare patient-ventilator interactions and Vt variability in premature infants recovering from respiratory distress syndrome (RDS) who were weaned by various ventilator modes (SIMV/PSV þ VG/SIPPV þ VG and SIMV þ VG). Methods: This was a short-term crossover trial in which each infant served as his/her own control. Ten premature infants born before the 32nd week of gestation in the recovery phase of RDS were enrolled in the study. All recruited infants started ventilation with SIPPV and in the weaning phase were switched to synchronized intermittent mandatory ventilation (SIMV). Baseline data were collected during an initial 20-min period of monitoring with the infant receiving SIMV alone, then they were switched to SIPPV þ VG for a 20-min period and then switched back to SIMV for 15 min. Next, they were switched to PSV þ VG for the study period and switched back to SIMV for a further 15 min. Finally, they were switched to SIMV þ VG and, at the end of monitoring, they were again switched back to SIMV alone. Results: Each mode combined with VG discharged comparable Vts, which were very close to the target volume. Among the VG-combined modes, mean variability of Vt from preset Vt was significantly different. Variability from the target value was significantly lower in SIPPV and PSV modes than in SIMV (P < 0.0001 and P < 0.04 respectively). SIPPV þ VG showed greater stability of Vt, fewer large breaths, lower respiratory rate, and allowed for lower peak inspiratory pressure than what was delivered by the ventilator during other modes. No significant changes in blood gases were observed after each of the study periods. Conclusions: With regards to the weaning phase, among combined modes, both of the ones in which every breath is supported (SIPPV/PSV) are likely to be the most effective in the delivery of stable Vt using a low working pressure, thus, at least in the short term, likely more gentle for the neonatal lung. In summary, we can suggest that the VG option, when combined with traditional, patient triggered ventilation, adheres very closely to the proposed theoretical algorithm, achieving highly effective ventilation.

Cystic ®brosis (CF) is the most common autosomal-recessive disease in Caucasians. Colonization with Pseudomonas aeruginosa (P. aeruginosa) of the CF airways causes deterioration of pulmonary status. TOBI R (Tobramycin solution for inhalation) is an inhaled antibiotic that can improve the pulmonary disease.

A double-blind study was performed to demonstrate that bronchodilator can be administered reliably to infants and children under 3 years of age from a metered-dose inhaler (MDI) by means of an economical valved aerosol-holding chamber device (Aerocharnberp fitted with a mask. Symptoms of cough and breathlessness were compared for two 1-week crossover periods with the child either taking active drug or placebo. The MDI and Aerochamber with mask is an effective delivery system for respiratory therapy in these young children. Pediatr Pulmonol. 1989; 6:263-267.

The objective of our study was to evaluate the pressurized metered dose inhaler (pMDI) with holding chamber technique of asthmatic children attending out patient pediatric chest clinic and determine factors associated with incorrect technique. All patients had previously received instructions regarding inhalation technique. The inhalation technique was assessed on a five-point checklist, four of which were considered essential. Two hundred and thirteen children (mean ± SD age, 7.3 ± 3.8 years; 151 boys) completed the study. Children were using their inhaler for a median duration of 6 months (range 1–96 months). One hundred and eighty-eight patients (88.3%) performed all essential steps correctly. The commonest mistake among the essential steps was not shaking the inhaler (n = 21, 9.9%) followed by inability to make a tight seal around the mouthpiece of the holding chamber (n = 12, 5.6%). Correct technique was not affected by gender, asthma severity and socio-economic indices: education level of parents, percapita monthly income, rural or urban background. Our study indicates that a large majority of children from a developing country setting, irrespective of lower education and income levels can be successfully educated to appropriately use inhalation device. Inhalation performance is not affected by socio-economic background of the patients. Comprehensive inhalation instructions and monitoring at each visit are however critical to ensure reliable and consistent performance of correct technique among asthmatic children. Pediatr Pulmonol. 2006, 41:1082–1087. © 2006 Wiley-Liss, Inc.

Background: Physiotherapists sometimes use elective surgical procedures for children with cystic fibrosis as an opportunity to perform physiotherapy treatments during anesthesia. These treatments theoretically facilitate direct endotracheal airway clearance and compensate for any post-operative respiratory deterioration related to the anaesthetic and surgery. Materials, patients, and methods: Children were randomized either to receive physiotherapy or not following anesthesia and intubation. Respiratory mechanics (C rs and R rs ), tidal volume, and peak inspiratory pressure (PIP) were measured immediately before and after physiotherapy. FEV 1 was measured before and after surgery and post-operative physiotherapy requirements were recorded. Results: Eighteen patients, mean age 12 years (range 2.8-15 years) were recruited, with nine in each group. Both groups showed a non-significant decline in FEV 1 the day after surgery compared with pre-operative values (À5.8%: physiotherapy and À7.1%: control). Both PIP and R rs increased significantly following physiotherapy (within-and between-groups, P < 0.05). In addition, there was a significant within-group reduction in C rs after physiotherapy which approached significance between-groups (P ¼ 0.07). There were no significant within-or between-group differences in tidal volume following treatment in either group. Conclusion: The unanticipated decline in respiratory function immediately following physiotherapy was short-lived and not discernible in longer term outcomes measured by FEV 1 or physiotherapy requirements post-operatively. If respiratory physiotherapy under anesthesia is considered necessary and the benefits of removing secretions are deemed to outweigh the short-term risks, it may be necessary for the anaesthetist to consider modifying ventilatory support to counteract any short-term negative effects of the treatment.

Objectives: To develop a simple, clinically meaningful radiographic score for bronchopulmonary dysplasia (BPD). To investigate its reliability, validity, and usefulness and to compare it to the Edwards score. Working hypothesis: Our radiographic scoring of BPD is reliable, correlates with respiratory support, and provides a necessary standardization in comparing severity of respiratory disease between hospitals. Study design: Prospective cohort study. Patient selection: The study included all neonates (n = 366) with birth weight below 1501 g admitted to 7 neonatal intensive care units, who had chest radiographs taken at age 25-35 days. Methodology: A simple radiographic scoring system was developed. Scores ranging from 0 to 6 were assigned based on standard radiographs and descriptors of degree of abnormality. All radiographs taken between days 25 and 35 of age (n = 1087) were graded by a radiologist and a neonatologist. Radiographs from a stratified random sample of 37 neonates (10%) were also scored by the method of Edwards (n = 128 radiographs). A respiratory support index was constructed for days 25-35 and correlated with the radiographic score. Results: Between-reader correlation was r = 0.87 for our score and r = 0.88 for the Edwards score. The two scores correlated with each other at r = 0.94. The respiratory support index correlated with our radiographic score at r = 0.75 overall, and r = 0.56 to 0.88 within hospitals. Higher postnatal coriicosteroid use was found at the hospitals with the lower correlations. Conclusions: Our radiographic scoring is reliable, valid, and gives results similar to the Edwards score. Radiographs play a standardizing role in assessing severity of BPD between hospitals.

Pulmonary function of children aged 6-1 8 years is described based on 82,462 annual measurements of forced vital capacity (FVC), forced expired volume in 1 second (FEV,), and forced expiratory flow between 25% and 75% of FVC (FEFZ5-,,%) from 11,630 white children and 989 black children. Median height, FVC, FEV,, FEVJFVC, and F E F , , , , for each 3 months of age are compared among race and sex subgroups. Race-and sex-specific percentile distributions of FVC, FEV,, FEVJFVC. and F E F , , . , , , are presented for each centimeter of height (growth curves). For the same height, boys have greater lung function values than girls, and whites have greater ones than blacks. Lung function increases linearly with age until the adolescent growth spurt at about age 10 years in girls and 12 in boys. The pulmonary function vs. height relationship shifts with age during adolescence. Thus, a single equation or the pulmonary function-height growth chart alone does not completely describe growth during the complex adolescent period. Nevertheless, race-and sex-specific growth curves of pulmonary function vs. height make it easy to display and evaluate repeated measures of pulmonary function for an individual child. Race-, sex-, and age-specific regression equations based on height are provided, which permit the evaluation of growth during adolescence with improved accuracy and, more importantly, in comparison with previous observations for the same child. Pediatr Pulmonol. 1993; 15:75-88. @I 1993 Wiley-Uss, Inc.

Background: Mechanical ventilation (MV) strategies are continuously evolving in an effort to minimize adverse events. The objective of this study was to determine the complications associated with MV in children. Study Design: Prospective observational study. Over a period of 10 consecutive months, 150 patients (median age 0.8 years, IQR 4.4, 59% male) were enrolled in this study. Results: The median duration of MV was 3.1 days (IQR 3.9). A total of 85 complications were observed in 60 (40%) patients (114 complications per 1,000 ventilation days). 16.7% of patients developed atelectasis, 13.3% post-extubation stridor, 9.3% failed extubation, 2.0% pneumothorax, 3.3% accidental extubation, 2.7% nasal or perioral tissue damage and 1.9% ventilator associated pneumonia. Atelectasis occurred most often in the left lower lobe (36%) or in the right upper lobe (26%). The incidence of atelectasis in children <1 year of age was 12% (31 episodes per 1,000 days of ventilation) compared to 18% (57 episodes per 1,000 days of ventilation) in children !1 year of age (P < 0.05). Patients that failed extubation were ventilated for a median of 8.5 (IQR 8.8) days compared to 2.9 days (IQR, 3.8) in patients that were successfully extubated (P < 0.01). The absence of an air leak prior to extubation did not correlate with failed extubation. Accidental extubation was limited to orally intubated patients. Conclusion: MV complications occurred in 40% of patients and most often consisted of atelectasis and post-extubation stridor. Further studies are needed to examine associated risk factors and strategies to reduce their occurrence.

Background: Little is currently known about the co-morbidity of depression and cystic fibrosis (CF) and there is currently no empirical research on the effects of depressive symptoms on adherence in children and adolescents with CF. The primary aim of this study was to evaluate the extent of depressive symptoms in children and adolescents with CF and their parents, and determine whether depressive symptoms in the child and/or parent was associated with adherence to airway clearance. We also evaluated whether children's perceptions of relational security with a parent were associated with adherence to airway clearance. Methods: Participants included 39 children with CF ages 7-17 years and their primary caregivers. Depressive symptoms were measured with the Children's Depression Inventory (CDI) and the Center for Epidemiological Studies-Depression Scale (CES-D). The Relatedness Questionnaire assessed the quality of parent-child relational security. Adherence to airway clearance was measured using the daily phone diary (DPD), an empirically validated adherence measure for youth with CF. Results: Rates of depressive symptoms were elevated in children with CF and their parents (29% for children; 35% for mothers; 23% for fathers). Child depressive symptoms were significantly associated with lower rates of adherence to airway clearance, after controlling for demographic variables (r ¼ À0.34, P ¼ 0.02). Child depressive symptoms were associated with worse perceptions of parental relationships (t(35) ¼ 3.2; P ¼ 0.002) and the quality of this relationship was also related to worse adherence (r ¼ 0.42, P ¼ 0.005). Conclusions: A large percentage of youth with CF and their parents reported elevated symptoms of depression. Children scoring in the depressed range on a standardized screening measure and those with less secure parent-child relationships were at greatest risk for poor adherence. Thus, depressive symptoms and family relationships are appropriate targets for adherence promotion interventions, which may ultimately improve health outcomes.

Purpose To understand potential benefits of exercise in the cystic fibrosis (CF) population, there needs to be accurate methods to quantify it. The Habitual Activity Estimation Scale (HAES) questionnaire has been shown to be a feasible tool to measure physical activity however the reliability and validity has yet to be determined in the CF population. Methods: Fourteen (seven male, seven female) patients aged 16.2 AE 4.2 years with CF participated in this study. Participants were clinically stable at the time of the study and participating in their habitual physical activity. To assess reliability, patients completed the HAES and a validated 3-day activity diary, and wore an ActiGraph TM Accelerometer for two consecutive weeks. Validity was assessed by comparing the activity results of each of the three instruments over a single week time period. Results: ICC estimates of reliability for the HAES, diary, and accelerometer were 0.72 (P < 0.0001), 0.76 (P < 0.0001), 0.63 (P < 0.0001), respectively. Validity analysis indicated that there were significant relationships between the participants' activity results as estimated by the HAES, diary and accelerometer. Further, significant relationships were detected between activity measures when broken into morning, afternoon, or evening periods, and between measures from weekday or weekend days. There were also significant relationships among the three instruments when recording different activity levels (somewhat inactive, somewhat active, and very active). Conclusion: The findings of this study suggest that the HAES questionnaire is a reliable and valid instrument that can be used to assess activities of varying intensity in patients with CF.

The primary molecular defect in most CF patients is caused by misfolding and subsequent degradation of ΔF508 CFTR. Phe508 is located in the first nucleotide binding domain (NBD1) of CFTR, where it decreases NBD1 folding efficiency (in cells), and thermodynamic stability (in vitro). In addition, the efficiency of NBD1 folding is a limiting factor in CFTR trafficking, which is further compromised by the ΔF508 mutation. An important goal in CF therapeutics, therefore, is to understand how NBD1 acquires and maintains its folded state in the cellular environment and to devise pharmacological strategies to improve folding efficiency. To address this problem, we developed a FRET-based method to define the de novo NBD1 folding pathway (Khushoo A, et al. Mol Cell. 2011;41:682-92). The ability to monitor NBD1 folding directly on the ribosome is appealing because it allows access to folding intermediates that exist only transiently during CFTR synthesis and thus provides a potential means to pharmacologically manipulate the cotranslational folding pathway. Cell free translation systems enable quantitative incorporation of fluorescent probes with extraordinary specificity and selectivity. However, the low concentration of protein obtained from stalled ribosomes is exceedingly low (~1nM). We therefore developed a solid-state system to immobilize His-tagged NBD1 ribosome-nascent-chain complexes (RNCs) on Ni agarose beads, which improves FRET sensitivity several orders of magnitude. With continued improvement of this method, we are now able to detect as little as 1 attomole (~650,000 molecules) of in vitro synthesized nascent NBD1 by fluorescence microscopy when immobilized at surface densities of 130 RNCs/μm 2 on 40 μm beads (~10% geometric saturation). A standard 250 μl translation reaction therefore yields sufficient material for a minimum of 100,000 separate fluorescent measurements. To validate this system, donor and/or donor+acceptor (1:1 stoichiometry) probes were cotranslationally incorporated into NBD1, and FRET was measured by imaging beads that contained truncated, ribosome-bound nascent polypeptides. Incorporation of the acceptor dye adjacent to the N-terminal CFP donor probe (residue 389) yielded approximately 65% FRET, in excellent agreement with solution-based studies. Placing the acceptor dye at residue 450 further demonstrated that immobilized NBD1 undergoes N-terminus subdomain folding as residues 500-550 move outside the ribosome tunnel and that kinetically trapped NBD1 can be folded on the bead upon ribosome release. Thus, solid-state measurements recapitulate nascent chain folding observed in solution with a >10,000 fold improvement in sensitivity. Currently, we are using high content microscopy to adapt this platform for high throughput screening of small molecules that interact with and stabilize nascent NBD1. (Supported by CFF and NIH DK51818.)

Objective: To analyze the initial experience in mechanical ventilation courses held by the Respiratory Group of the Spanish Paediatric Intensive Care Society. Materials and methods: From 2002 to 2006, 15 courses on paediatric mechanical ventilation were held in eight hospitals in Spain, attended by a total of 367 physicians (53.4 % trainees and 46.6 % staff physicians from Paediatrics, Neonatology or Emergency). An initial theoretical written test of 40 questions was completed by participants, followed by short theory classes and practical workshops based on clinical situations, with ventilators and ventilation simulators, with five to seven students per workshop. At the end of the course participants completed a theoretical written test, in which it was considered necessary to answer correctly at least 70% of the questions, a practical evaluation (with assessment grades from 1 to 5) and a written survey about the quality of the course (with assessment grades from 0 to 10). Results: In the initial test, only 20% of students answered 70% of questions correctly, whilst in the final test 93% hit this target, (p < 0.001). In the practical evaluation, 96% of students demonstrated sufficient acquisition of practical skills (grades equal to or greater than 3). In the participant survey, the course methodology was rated at 8.7 AE 0.5, organization 8.7 AE 0.4, teaching staff 9.2 AE 0.2, theoretical classes 8.7 AE 0.4, and practical sessions 8.8 AE 0.3. Conclusions: Mechanical ventilation courses are a useful educational method for health professionals in theoretical and practical mechanical ventilation.

Congenital central hypoventilation syndrome (CCHS) is an increasingly recognized diagnosis causing central hypoventilation and may be definitively diagnosed by genetic testing. Previous authors reported the association between CCHS and central sinus venous thrombosis (CSVT) and hypothesized that CCHS could be secondary to CSVT. We report a case of CCHS with the typical PHOX2B mutation who also suffered from CSVT. We assume that effects, secondary to CCHS, upon the central venous system may explain the etiological connection between CSVT and CCHS including dysautoregulation, venous stasis or polycythemia. We believe that CCHS should be included in the differential diagnosis of patients with CSVT accompanied by respiratory abnormalities.

Alveolar epithelial cells of neonates are directly exposed to aspirated meconium during meconium aspiration syndrome (MAS). This study was designed to investigate the influence of quantity and time of meconium exposure on the cell viability and caspase activity in type II human alveolar epithelial cells. Human alveolar epithelial cells were incubated with human meconium suspension at different concentrations and for different times. Cell viability and DNA fragmentation were investigated together with caspases activity and the amount of Bcl-2 protein present. We found that cell viability was significantly lower in cells exposed to a higher concentration of meconium. This was also true for cells exposed to meconium for longer. Significantly higher DNA fragmentation, an approximately two-to fivefold increase, was observed in cells that had been exposed to higher (5% and 10%) concentration of meconium compared to those treated with lower (0.1% and 1%) concentrations (P < 0.05). The activity of most apoptotic initiators (caspase 2, 8, 9, 10) and effectors (caspase 3, 6) were found to be significantly higher in cells subject to greater meconium exposure compared to cells with no or minor meconium exposure. The level of Bcl-2 was also found to be significantly decreased in meconium-exposed cells (P < 0.05). In conclusion, human meconium would seem to induce direct cell death as well as caspase-dependent apoptosis in alveolar epithelial cells; the amount and period of exposure to meconium are crucial factors in this process. Thus, removing aspirated meconium should alleviate lung cell damage in neonates and improve the outcome with MAS.

Background: Bronchial hyperresponsiveness (BHR), a characteristic feature of asthma, can be assessed through standardized bronchial provocation tests (BPT). Exercise as a BPT is used in diagnosing and monitoring exercise induced bronchoconstriction (EIB). Recently a novel osmotic BPT has been developed, using dry powder mannitol. The aim of this study was to investigate the clinical utility of the mannitol challenge to identify asthmatic children with EIB. Materials and Methods: Thirty-three clinically stable children, aged 9-18 years, with a history of EIB, performed both mannitol and exercise provocation challenges. Data were composed of a cross tabulation comparing the reaction on exercise provocation challenge to mannitol challenge. Correlations between post-exercise fall in FEV 1 and response-dose ratio (RDR) and PD 15 of mannitol were calculated. Results: Twenty-five children completed both tests. Pearson's correlation between log-transformed RDR for mannitol and post-exercise fall in FEV 1 was r p ¼ 0.666 (P < 0.001). There was no significant relationship between the log PD 15 of mannitol and post-exercise fall in FEV 1 . Children on long acting bronchodilator agents (LABA) were significantly (P < 0.05) more likely to have a positive response on the mannitol challenge. Positive and negative predictive values of the mannitol challenge for EIB were 69% and 91%. Conclusion: Mannitol challenge appears to be a suitable alternative for an exercise provocation test to assess EIB in asthmatic children. Given the negative predictive value of 91%, it is especially useful to exclude EIB.

Exhaled nitric oxide (NO) remains a promising non-invasive marker for measuring inflammation in lung diseases. In cystic fibrosis (CF), exhaled NO measured at a single expiratory flow has been found to be normal or low. However, this measure cannot localize the anatomical site of NO production. The aims of this study were to apply a multiple-flow NO analysis to compare alveolar NO concentration and bronchial NO flux in CF children with healthy controls. Twenty-two children with CF and 17 healthy controls had exhaled NO measured at four different expiratory flows to calculate bronchial NO flux and alveolar NO concentration. Median (range) alveolar NO concentration was 2.2 (0.6-5.6) ppb for children with CF and 1.5 (0.4-2.6) ppb for healthy controls. Median (range) bronchial NO flux was 445 (64-1,256) pL/sec for children with 913) pL/sec for healthy controls. Children with CF had a significantly higher alveolar NO concentration, but no significant difference in bronchial NO flux compared to healthy children. In conclusion, children with CF have increased alveolar NO production, but not bronchial NO flux compared to healthy controls. The distal airway is a major site of inflammation in CF, and measuring alveolar NO may be a marker of distal inflammation in this disease.

Recent developments in pulmonary function tests (PFTs) in preschool children (2-5 years of age) have meant that objective assessments of respiratory function are now possible for this age group. However, the application and interpretation of these tests may be limited by the relative paucity of appropriate reference equations. This review summarizes available preschool reference equations, identifies the current gaps and limitations in the methodologies and statistics used and proposes future directions for improving reference data. A PubMed search which included the MeSH terms (preschool [2-5years]), (respiratory function test), and (reference value) yielded 214 publications which were screened to identify 34 publications presenting 36 reference equations for seven techniques. There were considerable differences with respect to population characteristics, recruitment strategies, equipment and methodologies and reported parameters both within and between each measurement technique. Despite an increasing number of reference equations for PFT for preschool children, the extent to which these can be generalized to other populations may be limited in some cases by inclusion of relatively few children less than 5 years of age, a lack of details regarding the sample populations and measurement techniques and/or inappropriate statistical analysis. A fresh approach based on large sample sizes, clearly documented population characteristics, equipment and protocols, and more rigorous modern statistical methods both for developing reference equations and interpreting results could enhance clinical application of these tests. This in turn would maximize the tremendous opportunities to detect early lung disease offered by the recent surge in developing suitable tests for preschool children. Pediatr Pulmonol. 2007; 42:962-972. ß 2007 Wiley-Liss, Inc.

Objectives: Recurrent/persistent pneumonia in children continues to be a major challenge for the pediatricians. The aim of our study was to establish the prevalence and underlying causes of recurrent/persistent pneumonia in children in Upper Egypt. Settings: Assiut University Children Hospital, Assiut, Egypt. Patients and Methods: Patients, admitted for pneumonia to the hospital during 2 years, were investigated with microbiological, biochemical, immunological and radiological tests in order to establish the prevalence of recurrent/persistent pneumonia and to find out its underlying causes. Results: 113 out of 1228 patients (9.2%) met the diagnosis of recurrent /persistent pneumonia. Identified causes were; aspiration syndrome (17.7%), pulmonary TB (14.0%), congenital heart disease (11.5%), bronchial asthma (9.7%), immune deficiency disorders (8.8%) and vitamin D deficiency rickets (7.0%). Other causes included; congenital anomalies of the respiratory tract, interstitial lung diseases, bronchiectasis, and sickle cell anemia. No predisposing factors could be identified in 15% of cases. Conclusion: Approximately 1 out of 10 children with diagnosis of pneumonia in Assiut University Children Hospital had recurrent/persistent pneumonia. The most frequent underlying cause for recurrent/persistent pneumonia was aspiration syndrome, followed by pulmonary TB.

The aim of the present study was to evaluate if high-frequency oscillatory ventilation (HFOV) might reduce lung inflammation in preterm infants with infant respiratory distress syndrome (RDS) in comparison with the early application of another potentially lung-protective ventilation strategy, such as pressure support ventilation plus volume guarantee (PSV þ VG). Infants at less than 30 weeks of gestation with RDS were enrolled consecutively in the study if they required mechanical ventilation, and were randomly allocated to receive HFOV or PSV þ VG. Bronchial aspirate samples for the measurement of interleukin (IL)-1b, IL-8, and IL-10 were obtained before surfactant treatment (T1), after 6-18 hr of ventilation (T2), after 24-48 hr of ventilation (T3), and before extubation (T4). Thirteen patients were enrolled in the HFOV group, and 12 in the PSV þ VG group. The mean values of IL-1b, IL-8, and IL-10 at T4 were lower in the HFOV group than in the PSV þ VG group. The present study demonstrates that early treatment with HFOV is associated with a reduction of lung inflammation in comparison with PSV þ VG in preterm infants with RDS.

Background: Pulmonary dysfunction represents one of the most undervalued and less recognized complications in patients with b-thalassaemia. Objectives: The aim of this study was to assess the pattern of pulmonary dysfunction and consequently to investigate possible associated factors that might contribute to lung impairment in young patients with b-thalassaemia major. Methods: Fifty-two children and young adults (mean age: 21.33 AE 6.24 years) with b-thalassaemia major on conventional treatment (transfusions and iron chelation therapy) were included in the study. A complete computerized pulmonary function testing (PFT) system for recording pulmonary diffusion capacity and simultaneous determination of alveolar volume and pulmonary volumes was equipped. Results: Results showed that 20 patients (38.46%) had restrictive pulmonary pattern that was preferentially observed in older and shorter patients. Serum ferritin levels were higher in the restrictive group (2,096 AE 1,831 ng/dl) compared to patients with normal pulmonary function (1,354 AE 942 ng/ dl) (P ¼ 0.066). Diffusional impairment characterized by significantly lower DLCO Ã % values, was observed in the restrictive group (P ¼ 0.004), implicating the 62.5% of the population studied. Paired linear correlations showed that age was negatively correlated to DLCO Ã % (r ¼ À0.548, P < 0.001) and SaO 2 % (r ¼ À0.789, P < 0.001) and with most of the pulmonary functional parameters that determine a restrictive. Multivariate regression analysis identified age as the major predictor for restrictive pulmonopathy followed by serum ferritin levels. Conclusions: Our study shows that pulmonary impairment is shown in a great proportion even among asymptomatic young thalassaemic patients, thus, regular screening of pulmonary function should be adopted in the routine clinical follow up of these patients. Pediatr Pulmonol.

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. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

Children requiring home mechanical ventilation (HMV) represent a select group of technology-dependent patients. We evaluated the prevalence of children using invasive HMV in Utah from 1996 to 2004. Residents of Utah, 16 years old and less ventilated via a tracheostomy between 1996 and 2004 were identified. Children ventilated in 1996 and 2004 were compared. Data including demographic information, diagnosis leading to HMV, and age at initiation were compared between the two groups. The prevalence of HMV in 1996 was 5.0/100,000 (95% CI: 4.4-8.1) and 6.3/100,000 (95% CI: 4.7-8.4) in 2004. Median age at initiation was 6.5 months (IQR: 1.3, 24.0). Sixty-one percent (n ¼ 47) were male, 84% (n ¼ 65) lived in an urban county, and 86% (n ¼ 66) had public insurance. The most frequent diagnostic category was abnormal ventilatory control (n ¼ 36, 47%), followed by chronic lung disease (n ¼ 19, 25%), airway abnormalities (n ¼ 12, 16%), and neuromuscular weakness (n ¼ 10, 13%). Thirteen patients died (17%). The median length of HMV was 39 months (IQR: 15, 102). Diagnostic categories, age at initiation of HMV, and sex did not differ significantly over the 8 years. The prevalence of children requiring HMV differed very little between 1996 and 2004. Moreover, the diagnoses for which children received this therapy remained constant.

Objective: To evaluate the short and long-term clinical effects and the treatmentfeasibility of inhaled-furosemide (IF) as compared with placebo via hood in hospitalized infants with viral-bronchiolitis (VB). Study-Design: A randomized, double-blind, placebo-controlled pilot-study was performed in previously healthy infants (0-12 months). Enrolled infants were randomized to receive either IF (2 mg/kg), or placebo nebulized by hood three times daily throughout the hospitalization. Clinical assessment (respiratory distress assessment instrument [RDAI]) was performed before, 30 and 60 min after the 1st daily inhalation. The short-term effects were evaluated by the RDAI, respiratory assessment change score (RACS) and oxygen requirement and the long-term effects by time to be weaned off oxygen, time to full enteral feeding, length of stay, and ''ready to discharge'' time. Results: Both groups (16 infants each) had comparable characteristics at study entry. Mean (AESD) age was 72 AE 43 days, and 29/32 infants were RSV positive. Oxygen requirement (FiO 2 ) decreased significantly at 30 min post-inhalation (30 AE 9.2% to 26 AE 7.1%, P < 0.05) only in the IF group. RACSs and long-term effects of both groups were comparable. Analysis of IF particles generated by the hood-nebulizer demonstrated that 36% and 49% of the particles were <3 and 5 mm, respectively. No side effects were observed during IF treatment. Conclusion: Based on our pilot study, IF has no significant clinical effects in hospitalized infants with VB. IF via hood seems to be feasible and safe.

The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous Pop (tcP,,) of 0.5 kPa (P < 0.01); afler a second dose given 30 minutes later, the mean increase was 1.2 kPa (P < 0.001). The increase in tcPo, after only one dose of salbutamol was significantly correlated to age (P < 0.01). No such correlation was observed after a second dose. The overall increase in tcP,, after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P < 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction. Pediatr Pulmonol. 1992; 14:7!&79.

BACKGROUND:
As survival and outcomes continue to improve in neonates born prematurely, there is an increasing need to promptly identify and treat pulmonary hypertension (PHT) in this population. Several echocardiographic indices have been used to evaluate for PHT. There is no clear consensus on how to utilize these parameters specifically for the evaluation of PHT in infants with chronic lung disease of prematurity.
OBJECTIVES:
Τhe objectives of the study were (1) to identify the different echocardiographic techniques for assessment of PHT in infants with chronic lung disease of prematurity in an evidence-based manner and (2) to establish an echocardiographic screening protocol based on available literature using different echocardiographic techniques.
METHODS:
We conducted a systematic review of the literature regarding use of echocardiographic techniques for evaluation of PHT in infants with bronchopulmonary dysplasia. On the basis of the available evidence, we came up with a screening algorithm using various echocardiographic techniques.
RESULTS:
We identified nine techniques that had been employed for detection of PHT noninvasively using echocardiography in 23 studies. Using these echocardiographic parameters, we came up with a flow chart to diagnose PHT in infants born prematurely, based on presence or absence of tricuspid regurgitation, presence or absence of patent ductus arteriosus, and direction of flow.
CONCLUSIONS:
We have proposed a new screening strategy for assessment of PHT using echocardiography in infants with chronic lung disease of prematurity. Further studies will be necessary to confirm its validity.