Showing papers in "Pediatric Pulmonology in 2012"

Dysphagia and aspiration in children.

Abstract: Aspiration is a significant cause of respiratory morbidity and sometimes mortality in children. It occurs when airway protective reflexes fail, especially, when dysphagia is also present. Clinical symptoms and physical findings of aspiration can be nonspecific. Advances in technology can lead to early diagnosis of dysphagia and aspiration, and, new therapeutic advances can significantly improve outcome and prognosis. This report first reviews the anatomy and physiology involved in the normal process of swallowing. Next, the protective reflexes that help to prevent aspiration are discussed followed by the pathophysiologic events that occur after an aspiration event. Various disease processes that can result in dysphagia and aspiration in children are discussed. Finally, the various methods for diagnosis and treatment of dysphagia in children are reviewed.

A study of the use of impulse oscillometry in the evaluation of children with asthma: analysis of lung parameters, order effect, and utility compared with spirometry.

Abstract: Background The ability to objectively measure lung function in children is critical in the assessment and treatment of asthma in this age group. We thus determined the effectiveness of impulse oscillometry (IOS) as a non-invasive technique to assess lung function in children and in comparison to spirometry for sensitivity and specificity, testing variability, and the order effect of sequential testing of IOS and spirometry.

Hospital readmissions for newly discharged pediatric home mechanical ventilation patients

Abstract: Background Ventilator-dependent children have complex chronic conditions that put them at risk for acute illness and repeated hospitalizations.

Lung function decline from adolescence to young adulthood in cystic fibrosis.

Abstract: Background Despite improving survival in cystic fibrosis (CF) patients, there is a mortality peak in early adulthood Defining risk factors that predict significant worsening of lung disease in young adulthood may identify opportunities to improve outcomes in adults Methods We identified 4,680 patients in the Epidemiologic Study of Cystic Fibrosis 1994–2005 with data in both adolescence (age 140–174 years) and young adulthood (age 185–220 years) and analyzed 2,267 who had ≥5 encounters and ≥5 measurements of forced expiratory volume in 1 second (FEV1) spanning ≥1 year during both adolescence and young adulthood, and ≥1 encounter with weight and height and ≥1 FEV1 measurement age 175–185 years We compared the annualized rates of decline in FEV1 during adolescence and young adulthood stratified by best FEV1 around age 18 Logistic regression was used to identify risk factors associated with substantial decline (>20 points) in FEV1% predicted in young adulthood Results Annual rate of decline was greater in young adulthood than in adolescence Risk factors for substantial decline included slower rate of FEV1 decline, greater FEV1 variability, faster body mass index (BMI) decline, male sex, chronic inhaled antibiotics, Haemophilus influenzae detection, and absence of multidrug-resistant Pseudomonas aeruginosa in adolescence, and lower than expected FEV1 and BMI around age 18 Conclusions Decline in lung function accelerates in young adults with CF, especially in those with early stage lung disease Adolescents at risk for substantial decline in lung function in young adulthood have higher FEV1 and worse nutritional status, among other identifiable risk factors Pediatr Pulmonol 2012; 47:135–143 © 2011 Wiley Periodicals, Inc

Managing treatment complexity in cystic fibrosis: challenges and opportunities.

Abstract: 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 co-morbidities as patients reach older ages, leading to the need for a highly complicated and time-consuming 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.

Lower airway microbiology and cellularity in children with newly diagnosed non-CF bronchiectasis

Abstract: Background: Infection and inflammation are important in the pathogenesis of bronchiectasis. However, there are few published data describing the lower airway microbiology and cellularity in children. Methods: Children with non-cystic fibrosis (CF) bronchiectasis who underwent bronchoalveolar lavage (BAL) within 4 weeks of diagnosis were identified by a retrospective patient-record review. The effects of infection (>= 10(5) colony-forming units of respiratory bacteria/ml; or detectable Pseudomonas aeruginosa; mycobacteria, fungi, mycoplasma, or respiratory viruses) on airway cellularity and the impact of age, gender, indigenous status, immune function, radiographic involvement and antibiotic usage on infection risk were evaluated. Results: Of 113 children [ median age 63 months (IQR 32-95)] with newly diagnosed bronchiectasis, 77 (68%) had positive BAL cultures for respiratory bacterial pathogens. Haemophilus influenzae was most commonly detected, being present in 53 (47%) BAL specimens. P. aeruginosa was found in just 7 (6%) children, five of whom had an underlying disorder, while mycobacterial and fungal species were not detected. Respiratory viruses were identified in 14 (12%) children and Mycoplasma pneumoniae in two others. Overall, 56 (49.5%) children fulfilled our definition of a lower airway infection and of these, 35 (63%) had more than one pathogen present. Compared to children without infection, children with infection had higher total cell counts (610 vs. 280 X 10(6)/L), neutrophil counts (351 vs. 70 X 10(6)/L), and neutrophil percentages (69% vs. 34%). Age at diagnosis was most strongly associated with infection. Conclusions: BAL microbiology of children with newly diagnosed bronchiectasis is dominated by H. influenzae. In the absence of CF, isolation of P. aeruginosa may suggest a serious comorbidity in this group. Airway neutrophilia is common, especially with higher bacterial loads. Pediatr Pulmonol. 2012; 47:300-307. (C) Wiley Periodicals, Inc.

Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis

Abstract: BACKGROUND: The clinical relevance of parallel detection of multiple viruses by real-time polymerase chain reaction (RT-PCR) remains unclear. This study evaluated the association between the detection of multiple viruses by RT-PCR and disease severity in children with bronchiolitis. METHODS: Children less than 2 years of age with clinical symptoms of bronchiolitis were prospectively included during three winter seasons. Patients were categorized in three groups based on disease severity; mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). Multiplex RT-PCR of 15 respiratory viruses was performed on nasopharyngeal aspirates. RESULTS: In total, 142 samples were obtained. Respiratory Syncytial virus (RSV) was the most commonly detected virus (73%) followed by rhinovirus (RV) (30%). In 58 samples (41%) more than one virus was detected, of which 41% was a dual infection with RSV and RV. In RSV infected children younger than 3 months, disease severity was not associated with the number of detected viruses. Remarkably, in children older than 3 months we found an association between more severe disease and RSV mono-infections. CONCLUSION: Disease severity in children with bronchiolitis is not associated with infection by multiple viruses. We conclude that other factors, such as age, contribute to disease severity to a larger extent.

Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution

Abstract: Background Though tobramycin inhalation solution has been used for over a decade to improve lung function and reduce exacerbations in patients with cystic fibrosis (CF), its effects on mortality have not been well-described. This study aimed to assess the association between use of tobramycin inhaled solution and mortality in patients with CF and chronic Pseudomonas aeruginosa (PA) infection. Methods Longitudinal logistic regression was used to assess the association between current-year reported use of tobramycin inhalation solution and subsequent-year mortality of patients meeting recommended criteria for tobramycin inhalation solution use in the United States Cystic Fibrosis Foundation's Patient Registry (1996–2008). Results Among 12,740 patients meeting inclusion criteria, 2,538 deaths were observed during a median follow-up of 6 years. After regression adjustment, use of tobramycin inhaled solution was associated with a 21% reduction in the odds of subsequent year mortality (odds ratio (95% CI): 0.79 (0.72–0.88), P < 0.001). In our model, use of dornase alfa was also associated with a 15% reduction in the odds of subsequent year mortality (odds ratio (95% CI): 0.85 (0.76–0.95), P = 0.005). Underweight for age, CF-related diabetes, female gender, worse lung function and cultures positive for Pseudomonas aeruginosa or Burkholderia cepacia complex, among multiple other patient characteristics, were associated with significantly increased mortality. Adjusted mortality rates for patients reporting tobramycin inhalation solution use in all versus none of the follow-up years were 1.3% versus 2.1% at 2 years, 5.2% versus 8.0% at 5 years, and 9.9% versus 15.0% at 10 years. Conclusion After adjustment for multiple patient characteristics and known risk factors, use of tobramycin inhalation solution was associated with significantly reduced mortality among patients with CF. Pediatr Pulmonol. Pediatr Pulmonol. 2012; 47:44–52. © 2010 Wiley Periodicals, Inc.

Comparison of pressure-, flow-, and NAVA-Triggering in pediatric and neonatal ventilatory care†‡

Abstract: Summary. Objective: To compare conventional trigger modes (pressure and flow trigger) to neurally adjusted ventilatory assist (NAVA), a novel sensing technique, and to observe the patient-ventilator interactions during these modes. Methods: In this prospective, crossover comparison study in tertiary care pediatric and neonatal intensive care unit, 18 patients (age from 30 weeks of postconceptional age to 16 years) needing mechanical ventilation were randomized. Three patients were excluded from the analysis because of problems in data collection. Patients were ventilated with three different trigger modes (pressure, flow, NAVA), for 10 min each. Patients were randomly allocated to six groups according to the order of trigger modes used. Results: The primary end point was the time in asynchrony between the patient and the ventilator. Secondary end points were peak and mean airway pressures (MAP), breathing frequency, tidal volume (TV), and vital parameters during each trigger mode. The proportion of time in asynchrony was significantly shorter in the NAVA group (8.8%) than in the pressure (33.4%) and flow (30.8%) groups (P < 0.001 for both). In the NAVA group, the peak inspiratory pressure was 2 to 1.9 cmH2O lower than in the pressure and flow groups, respectively (P < 0.05 for both) and the breathing frequency was 10 breaths/min higher than in the pressure group (P ¼ 0.001). There was a tendency toward a lower MAP (P ¼ 0.047) but the mean TV was about the same (6.4–6.8 ml/kg) in all three groups (P ¼ 0.55). There were no differences in oxygen saturation or vital parameters between the groups. Conclusion: NAVA offers a novel way of sensing patients’ spontaneous breathing and significantly improves short-term patient-ventilator synchrony in a pediatric population. Pediatr Pulmonol. 2012;

Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis.

Abstract: Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown.

Impaired behavioral and neurocognitive function in preschool children with obstructive sleep apnea.

Abstract: OBJECTIVE: We aimed to examine the hypothesis that behavioral and neurocognitive functions of preschool children with Obstructive Sleep Apnea Syndrome (OSAS) are impaired compared to healthy children, and improve after adenotonsillectomy (TA). METHODS: A comprehensive assessment battery was used to assess cognitive and behavioral functions, and quality of life in children with OSAS compared to matched controls. RESULTS: 45 children (mean age 45.5 ± 9 months, 73% boys, BMI 15.7 ± 2) with OSAS were compared to 26 healthy children (mean age 48.6 ± 8 months, 46% boys, BMI 16.4 ± 2). Mean AHI in the OSAS group was 13.2 ± 10.7 (ranging from 1.2 to 57). Significantly impaired planning and fluency (executive function) were found in children with OSAS, as well as impaired attention and receptive vocabulary. Parents and teachers described the OSAS group as having significantly more behavior problems. Quality of life questionnaire in children with OSAS (mean 2.3, range 0.7-4.3) was significantly worse compared to controls (mean 0, range: 0-4), P Language: en

Global impact of asthma on children and adolescents' daily lives: the room to breathe survey.

Abstract: Objective: To establish children and adolescents' perspectives regarding their asthma and its impact upon their daily lives. Design: A 14-item questionnaire. Setting: Canada, Greece, Hungary, The Netherlands, the United Kingdom, and South Africa. Participants: Children/adolescents (aged 8-15 years) with physician-diagnosed asthma. Intervention: Interviews were conducted by telephone (Canada, Greece, Hungary, The Netherlands, and the United Kingdom) or face-to-face (South Africa). Outcome Measures: Asthma symptoms, impact on activities, and quality of life. Results: Of the 943 children/adolescents interviewed, 60% were male. Most (81%) described their asthma as "not too bad" or "I only get it every now and then," with only 4% reporting their asthma as being "very bad"; however, 92% experienced asthma-related coughing and 59% reported nocturnal awakening. Over half (57%) of children/adolescents believed they could predict when their asthma would make them ill; the most common initial symptoms being breathlessness (41%) and bad cough (33%). They considered the worst things about having asthma to be the symptoms of an asthma attack (32%) and not being able to play sport (25%). Almost half (47%) of children/adolescents felt that their asthma affected their ability to play sport or engage in physical activity. One in ten reported they had suffered asthma-related bullying. Conclusions: Children/adolescents underestimate the severity of their asthma, and overestimate its control, indicating that they expect their illness to be symptomatic. Asthma has a substantial impact on their daily lives, particularly on physical activity and social functioning. Efforts are required to improve asthma control and expectations of health in children/adolescents. Pediatr Pulmonol. 2012; 47:346-357. (C) 2011 Wiley Periodicals, Inc.

Defining pulmonary exacerbation in children with non-cystic fibrosis bronchiectasis.

Abstract: Rationale Exacerbations in non-cystic fibrosis (CF) bronchiectasis are associated with worsening lung functions and quality of life. A standardized definition of exacerbation could improve clinical care and research. Methods: A cohort of 69 children with non-CF bronchiectasis was prospectively followed for 900 child-months. The changes in clinical, systemic, and lung function parameters from 81 exacerbations were statistically evaluated using conditional logistic regression, receiver operating characteristic, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) to formulate a definition of a pulmonary exacerbation. Formation of major and minor criteria was statistically based and models were developed. Measurements and Main Results: Wet cough and cough severity (score >= 2) over 72-hr were the best predictors of an exacerbation with area under the curve (AUC) of 0.85 (95% CI 0.79-0.92) and 0.84 (95% CI 0.77-0.91), respectively. Sputum color, chest pain, dyspnea, hemoptysis, and chest signs were significant though minor criteria. Inclusion of serum C-reactive protein, amyloid-A, and IL6 to the definition improved its specificity and PPV. Our final combined model consisted of one major with one investigatory criterion (PPV 91%, NPV 72%); two major criteria (PPV 79%, NPV 91%); or one major and two minor criteria (PPV 79%, NPV 94%). Conclusions: Pulmonary exacerbation in children with non-CF bronchiectasis can be validly predicted using a standardized assessment of clinical features, with additional systemic markers improving predictive values. This definition potentially facilitates earlier detection (leading to appropriate management) of exacerbations. Pediatr Pulmonol. 2012; 47: 68-75. (C) 2011 Wiley Periodicals, Inc.

Frontiers in pulmonary hypertension in infants and children with bronchopulmonary dysplasia.

Abstract: Pulmonary hypertension (PH) is an increasingly recognized complication of premature birth and bronchopulmonary dysplasia (BPD), and is associated with increased morbidity and mortality. Extreme phenotypic variability exists among preterm infants of similar gestational ages, making it difficult to predict which infants are at increased risk for developing PH. Intrauterine growth retardation or drug exposures, postnatal therapy with prolonged positive pressure ventilation, cardiovascular shunts, poor postnatal lung and somatic growth, and genetic or epigenetic factors may all contribute to the development of PH in preterm infants with BPD. In addition to the variability of severity of PH, there is also qualitative variability seen in PH, such as the variable responses to vasoactive medications. To reduce the morbidity and mortality associated with PH, a multi-pronged approach is needed. First, improved screening for and increased recognition of PH may allow for earlier treatment and better clinical outcomes. Second, identification of both prenatal and postnatal risk factors for the development of PH may allow targeting of therapy and resources for those at highest risk. Third, understanding the pathophysiology of the preterm pulmonary vascular bed may help improve outcomes through recognizing pathways that are dysregulated in PH, identifying novel biomarkers, and testing novel treatments. Finally, the recognition of conditions and exposures that may exacerbate or lead to recurrent PH is needed to help with developing treatment guidelines and preventative strategies that can be used to reduce the burden of disease.

Developmental and genetic aspects of congenital diaphragmatic hernia

Abstract: Congenital diaphragmatic hernia (CDH) is a frequent occurring cause of neonatal respiratory distress and occurs 1 in every 3,000 liveborns. Ventilatory support and pharmaceutical treatment of the co-occurring lung hypoplasia and pulmonary hypertension are insufficient in, respectively, 20% of isolated cases and 60% of complex ones leading to early perinatal death. The exact cause of CDH remains to be identified in the majority of human CDH patients and prognostic factors predicting treatment refraction are largely unknown. Their identification is hampered by the multifactorial and heterogenic nature of this congenital anomaly. However, application of high-resolution molecular cytogenetic techniques to patients' DNA now enables detection of chromosomal aberrations in 30% of the patients. Furthermore, recent insights in rodent embryogenesis pointed to a specific disruption of the early mesenchymal structures in the primordial diaphragm of CDH-induced offspring. Together, these data allowed for the introduction of new hypotheses on CDH pathogenesis, although many issues remain to be resolved. In this review, we have combined these new insights and remaining questions on diaphragm pathogenesis with a concise overview of the clinical, embryological, and genetic data available. Pediatr Pulmonol. 2012; 47:534–545. © 2012 Wiley Periodicals, Inc.

Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. aztreonam and carbapenems†‡

Abstract: Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem–cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200–300 mg/kg/day divided every 6 hr, maximum 8–12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance. Pediatr Pulmonol. 2012; 47:1147–1158. © 2012 Wiley Periodicals, Inc.

Interdisciplinary therapy improves biomarkers profile and lung function in asthmatic obese adolescents

Abstract: Summary. Background: The simultaneous rise in the prevalence of asthma and obesity in the world, have demonstrated the importance of the development of treatment strategies. The purpose of this study was to evaluate the short- and long-term results of interdisciplinary therapy on inflammatory biomarkers and lung function in asthmatics obese adolescents. Methods: Seventy-six post-pubertal obese adolescents were recruited, including 50 non-asthmatics [body mass index (BMI), 36 � 5 kg/m 2 ) and 26 asthmatics (BMI, 39 � 4 kg/m 2 ). Body composition was measured by plethysmography, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin, leptin, and C-reactive protein (CRP) were analyzed. Asthma and lung function were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1-year weight loss interdisciplinary intervention consisting of medical, nutritional, exercise, and psychological therapy. Results: After interdisciplinary intervention, the lung function and pro/anti-inflammatory adipokines improved significantly in both groups. Most importantly, there was an increase in adiponectin [4 (1.86–12.9) to 5.1 (2.48–16)], a reduction in CRP [2,073 (385–9,174) to 1,538 (205–7,083)] and leptin concentrations [59 (29–69) to 33 (9–49)] in the asthmatics patients. Furthermore, it was observed a reduction in asthma severity after treatment. In addition, D adiponectin was an independent factor to improve lung function after therapy in both groups. Conclusions: Interdisciplinary therapy resulted in beneficial changes in inflammatory biomarkers profile and lung function in asthmatic and non-asthmatic obese adolescents. Additionally, for the first time we showed that change in adiponectin level was an independent predictor to improve lung function in Brazilian obese adolescents.

Progression of lung disease in primary ciliary dyskinesia: is spirometry less accurate than CT?

Abstract: Despite its extensive use, there is no evidence that spirometry is useful in the assessment of progression of lung disease in primary ciliary dyskinesia (PCD). We hypothesize that high-resolution computed tomography (HRCT) is a better indicator of PCD lung disease progression than spirometry. We retrospectively evaluated two paired spirometry and HRCT examinations from 20 PCD patients (age, 11.6 years; range, 6.5–27.5 years). The evaluations were performed in stable state and during unstable lung disease. HRCT scans were scored blind by two raters. Compared to the first assessment, at the second evaluation spirometry did not change while HRCT scores significantly worsened (P < 0.01). Age was significantly related to HRCT total (r = 0.5; P = 0.02) and bronchiectasis scores (r = 0.5; P = 0.02). At both evaluations, HRCT total score correlated with FEV1 (r = −0.5, P = 0.01; r = −0.7, P = 0.001, respectively) and FVC Z scores (r = −0.6, P = 0.006; r = −0.7, P = 0.001, respectively), and bronchiectasis score was related to FEV1 (r = −0.5, P = 0.03; r = −0.6; P = 0.002, respectively) and FVC Z scores (r = −0.6, P = 0.008; r = −0.7, P = 0.001, respectively). No relationship was found between the change in HRCT scores and the change in spirometry. In PCD, structural lung disease may worsen despite spirometry being stable. Pediatr Pulmonol. 2012; 47:498–504. © 2011 Wiley Periodicals, Inc.

Non-invasive ventilation for severe bronchiolitis: analysis and evidence

Abstract: Objectives (1) To examine whether infants with severe bronchiolitis, fulfilling criteria for further respiratory support, could be managed outside a Pediatric Intensive Care Unit (PICU) with non-invasive ventilation (NIV) alone. (2) To study the characteristics, clinical course and outcome of NIV responders and non responders to assess safety and efficacy and inform guideline construction. Hypothesis Infants with severe bronchiolitis can be safely managed with NIV outside a PICU. Study Design Retrospective case review. Patient Selection Cohort of infants with objective evidence of severe bronchiolitis requiring respiratory support nursed in a Pediatric High Dependency Unit (PHDU) and/or Intensive Care Unit (ICU) between 2001 and 2007. Methodology Analysis of patient characteristics and respiratory parameters at admission and initiation of ventilation, changes after 2 and 4 hr of NIV or invasive ventilation, complications, short and long-term outcomes were analyzed. Results One thousand and thirty-five infants with bronchiolitis were admitted with 67 ventilation episodes identified from 65 patients. Fifty-five episodes, including 34 with apnea, were treated exclusively with NIV. Six infants failed to respond and were invasively ventilated. Six patients were invasively ventilated at presentation. Non-responders had a significantly higher rate of bacterial infection. Significant improvements in respiratory parameters in responders occurred by 2 hr and sustained at 4 hr. Duration of hospital stay, ventilation requirement and oxygen requirement were significantly shorter in responders. Short and longer-term follow up data did not identify any adverse effects related to NIV. Conclusions NIV was effective in 80% of infants receiving respiratory support for severe bronchiolitis. Pediatr Pulmonol. 2012. 47:909–916. © 2012 Wiley Periodicals, Inc.

Longitudinal lung function and structural changes in children with primary ciliary dyskinesia

Abstract: Background and Objectives Functional and structural lung evaluations are part of the follow-up of patients with primary ciliary dyskinesia (PCD). We aimed to evaluate transversal and longitudinal relationships between lung function test (LFT) and chest computed tomography (CT) in children with PCD, in stable clinical condition. Materials and Methods Data from children followed in the French National Center were retrospectively collected. Inclusion criteria were (i) definitive diagnosis of PCD, (ii) age less than 15 years at the beginning of follow-up, (iii) at least 8 years of follow-up, (iv) at least two couples of concurrent CT and LFT available in a phase of clinical stability of the lung disease without modification of the treatment regimen in the last 4 weeks. Twenty children (median age at entry 4.6 years, median follow-up 15.4 years) were included. Concurrent LFT (blood gas and spirometry) and CT (score) results were recorded. Results LFT indices (PaO2 (n = 210), FVC, FEV1, FEF2575% (n = 195)) significantly decreased with age, and the mean annual decrease (z-score (% predicted)) was −0.17 (−0.49%), −0.09 (−0.50%), −0.10 (−0.89%), and −0.07 (−1.73%), respectively. First CT (median age 8.7 years) revealed bronchiectasis (70%), mucous plugging (70%), peribronchial thickening (90%), parenchymal abnormalities (65%), and hyperinflation (50%). CT scores (n = 74) significantly increased with age, and was negatively correlated to PaO2, FVC, FEV1, and FEF2575% longitudinal changes. Conclusion In stable clinical condition, functional, and structural progressive impairments significantly correlated in children with PCD. Further prospective studies, including large populations of patients with various levels of disease severity, are needed to confirm whether lung function follow-up can be used to adjust CT frequency and help at minimizing the radiation burden in children with a good life expectancy. Pediatr Pulmonol. 2012. 47:816–825. © 2012 Wiley Periodicals, Inc.

Bronchiectasis in chronic pulmonary aspiration: risk factors and clinical implications.

Abstract: Introduction Bronchiectasis is a well-known sequela of chronic pulmonary aspiration (CPA) that can result in significant respiratory morbidity and death. However, its true prevalence is unknown because diagnosis requires high resolution computed tomography which is not routinely utilized in this population. This study describes the prevalence, time course for development, and risk factors for bronchiectasis in children with CPA. Materials and Methods Using a cross-sectional design, medical records were reviewed for all patients with swallow study or airway endoscopy-confirmed aspiration in our airway center over a 21 month period. All patients underwent rigid and flexible bronchoscopy, and high resolution chest computed tomography. Prevalence, distribution, and risk factors for bronchiectasis were identified. Results One hundred subjects age 6 months to 19 years were identified. Overall, 66% had bronchiectasis, including 51% of those less than 2 years old. The youngest was 8 months old. Severe neurological impairment (OR 9.45, P < 0.004) and history of gastroesophageal reflux (OR 3.36, P = 0.036) were identified as risk factors. Clinical history, exam, and other co-morbidities did not predict bronchiectasis. Sixteen subjects with bronchiectasis had repeat chest computed tomography with 44% demonstrating improvement or resolution. Discussion Bronchiectasis is highly prevalent in children with CPA and its presence in young children demonstrates that it can develop rapidly. Early identification of bronchiectasis, along with interventions aimed at preventing further airway damage, may minimize morbidity and mortality in patients with CPA. Pediatr Pulmonol. 2012; 47:447–452. © 2011 Wiley Periodicals, Inc.

The impact of reflux burden on Pseudomonas positivity in children with Cystic Fibrosis

Abstract: Objectives Nonacid gastroesophageal reflux (GER), particularly in patients taking acid suppression, has been implicated as a cause of respiratory infections. We hypothesize that children with cystic fibrosis (CF) and a higher nonacid reflux burden have greater rates of Pseudomonas aeruginosa (Pa) infection than patients with a lower reflux burden. Study Design We reviewed the multichannel intraluminal impedance (pH-MII) tracings of 35 patients with CF between 2003 and 2010. We compared the reflux profiles between those patients who were Pa positive and Pa negative. Results The mean age was 13.5 ± 5.8 years. Twenty-seven patients (76%) were Pa positive. Ninety seven percent of patients were taking proton pump inhibitors during pH-MII testing. The mean percentage of time pH was <4 was 8.5 ± 12%. Pa patients had a significantly higher total, acid and proximal nonacid reflux burden (P < 0.009). There was a negative correlation between nonacid reflux burden and FEV1 (r = −0.397, P = 0.03) and between total number of reflux events and FEV1 (r = −0.474, P = 0.009). After adjusting for age and FEV1, total reflux burden remains significantly associated with Pa positivity (P = 0.055). Conclusions Increased reflux burden may predispose patients to Pa infection and worse lung function. Pediatr Pulmonol. 2012; 47:582–587. © 2011 Wiley Periodicals, Inc.

Variable human phenotype associated with novel deletions of the PHOX2B gene

Abstract: Background Clinical testing for PHOX2B mutations is widely used for patients with any symptoms suggestive of hypoventilation (with/without anatomic/physiologic autonomic dysregulation), though not necessarily with the congenital central hypoventilation syndrome (CCHS) phenotype. Consequently, a multitude of referrals for clinical PHOX2B testing (fragment analysis of the 20 polyalanine repeat region and/or sequencing of entire coding region) have no identifiable mutation. Whole gene deletions/duplications have recently been identified as a common disease-causing mechanism, but have not been reported in a clinical population referred for PHOX2B testing. The objective of this study was to determine if PHOX2B exon or whole gene deletion/duplication would be identified in a subset of patients referred for PHOX2B testing. The objective of this study was to determine if PHOX2B exon or whole gene deletion/duplication would be identified in a subset of patients referred for PHOX2B testing. Hypothesis: We hypothesized that PHOX2B exon or whole gene deletion or duplication would be identified in a subset of cases who were referred for genetic testing but not found to have a PHOX2B mutation with currently available clinical PHOX2B testing. Methods: Genomic DNA samples from patients that tested negative for PHOX2B mutations using fragment analysis and/or sequencing, and control samples, were screened for PHOX2B exon deletions/duplications by multiplex ligation-dependent probe amplification with confirmation by array comparative genomic hybridization. Results: Deletions of/in PHOX2B were identified in 4/250 patients and 0/261 controls. The deletions ranged from 6,216 base pairs (involving only PHOX2B exon 3) to 2.6 megabases (involving all of PHOX2B and 12 other genes). The case with PHOX2B partial exon 3 deletion had a CCHS-compatible phenotype (hypoventilation, Hirschsprung disease). Phenotypes for the other three cases, all PHOX2B whole-gene deletions, were varied including: (1) apparent life threatening event, (2) full CCHS necessitating artificial ventilation with ganglioneuroblastoma, and (3) hypoventilation during sleep. Family studies of two of the four probands showed these deletions to be maternally inherited; the mothers also had phenotypic findings of autonomic dysfunction. Conclusions: PHOX2B exon or whole gene deletion should be considered as another mechanism of disease which may include CCHS, Hirschsprung disease, and/or tumors of neural crest origin, although the genotype-phenotype relationship requires further clarification. Pediatr Pulmonol. 2012; 47: 153-161. (C) 2011 Wiley Periodicals, Inc.

Assessment of f/hn-pseudotyped lentivirus in a clinically relevant vector for lung gene therapy

Abstract: RATIONALE Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved. METHODS F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air-liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices. MEASUREMENTS AND MAIN RESULTS A single dose produces lung expression for the lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials.

Bronchoscopic techniques for removal of foreign bodies in children's airways.

Abstract: Introduction The management of airway foreign bodies (AFB) can be a dramatic situation in the emergency treatment of children and different techniques have been used to improve the therapeutic success and minimize risks. Objective to describe the bronchoscopic techniques used in the treatment of AFB in children referred to the Service of Respiratory Endoscopy of HC-FMUSP. Patients and methods Retrospective analysis of 78 children who underwent bronchoscopy for foreign body removal, at our Service from February 2003 to April 2008. Results 78 patients with an AFB, aged 08 months to 14 years, with 39 being organic and 39 inorganic foreign bodies. Nine foreign bodies were located in the central airway (four in the larynx and five in the trachea), 34 in the right bronchial tree and 33 in the left bronchial tree. There was bilateral aspiration in two cases. All patients were initially submitted to diagnostic flexible bronchoscopy. A rigid bronchoscope was used in 39 cases; a flexible bronchoscope in 23 and an association of techniques in 15 cases (rigid bronchoscopy, flexible bronchoscopy, suspension laryngoscopy, and fluoroscopy). Discussion Although the rigid bronchoscopy is considered the main tool for the removal of foreign bodies from airways, other useful techniques deserve attention as part of the medical training. Conclusion The knowledge and association of different methods in pediatric bronchoscopy add the benefits of one method to another, minimizing the chances of therapeutic failure. Pediatr Pulmonol. 2012; 47:59–62. © 2010 Wiley Periodicals, Inc.

Assessing asthma control: symptom scores, GINA levels of asthma control, lung function, and exhaled nitric oxide.

Abstract: Background The childhood asthma control test (C-ACT) is a validated symptom score for assessing asthma control in children. We used a slightly modified version (C-ACTM) of the German C-ACT and compared our results with the literature, correlated the children's part of C-ACT (C-ACTchildren) with a visual analogue scale (VASchildren), explored the agreement between C-ACTM and GINA levels of asthma control, as well as the relationship between C-ACTM and lung function and exhaled nitric oxide (FeNO). Methods We investigated 107 children with a diagnosis of asthma. The study protocol consisted of a clinical examination, assessment of asthma control according to GINA guidelines, administration of C-ACTM, VASchildren, lung function, and FeNO. Results Of our patients 66% had, according to GINA, partly controlled-/uncontrolled asthma, 18% were uncontrolled according to C-ACTM. Children with partly controlled-/uncontrolled asthma according to GINA had lower C-ACTM scores than did children with controlled asthma (16.1 ± 3.6 SD vs. 25.4 ± 1.8 SD; P < 0.000), and children with a C-ACTM score ≤ 19 had poorer lung function (mean FEV1% predicted 81.5 ± 13.5 SD vs. 94.2 ± 12.1 SD; P = 0.002). Spearman's rank correlation coefficients revealed significant correlations between all symptom scores. Multiple linear regression adjusted for age, gender, FEV1 and FeNO demonstrated a significant relationship between C-ACTM, VASchildren, and FEV1 (P = 0.003, resp. <0.000), but no significant correlation between C-ACTM, VASchildren, and FeNO. Conclusions The German version of C-ACTM is valid and useful for monitoring children with asthma along with tests aimed to follow up lung function and airway inflammation. Concordance between C-ACTM and GINA is moderate, because asthma control assessed by C-ACTM allows more symptoms and lung function is not included in the scoring. Pediatr Pulmonol. 2012; 47:113–118. © 2011 Wiley Periodicals, Inc.

Lung function among infants born preterm, with or without bronchopulmonary dysplasia.

Abstract: 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 28+ weeks of gestation. Results BPD was associated to significantly lower flows (regression coefficients: −0.51, −0.54, −57, −0.53, and −0.82, respectively for FEF50, FEF75, FEF85, FEF25–75). This association was driven by males and maintained in the subgroup of infants born at 28+ 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. 2012; 47:674–681. © 2011 Wiley Periodicals, Inc.

Internet-based self-management compared with usual care in adolescents with asthma: A randomized controlled trial†‡

Abstract: Introduction Asthma control often is poor in adolescents and this causes considerable morbidity. Internet-based self-management (IBSM) improves asthma-related quality of life in adults. We hypothesized that IBSM improves asthma-related quality of life in adolescents. Methods Adolescents (12–18 years) with persistent and not well-controlled asthma participated in a randomized controlled trial with 1 year follow-up and were allocated to IBSM (n = 46) or usual care (UC, n = 44). IBSM consisted of weekly asthma control monitoring with treatment advice by a web-based algorithm. Outcomes included asthma-related quality of life (Pediatric Asthma Quality of Life Questionnaire, PAQLQ) and asthma control (Asthma Control Questionnaire, ACQ) and were analyzed by a linear mixed-effects model. Results At 3 months, PAQLQ improved with 0.40 points (95% CI: 0.17–0.62, P < 0.01), by IBSM compared to 0.0 points for UC (P = 0.02 for the difference). At 12 months the between-group difference was −0.05 (95% CI: −0.50 to 0.41, P = 0.85). At 3 months ACQ improved more in IBSM than in UC (difference: −0.32 points; 95% CI: −0.56 to −0.079, P < 0.01). At 12 months the difference was −0.05 (95% CI: −0.35 to 0.25, P = 0.75). Conclusion IBSM improved asthma-related quality of life and asthma control in adolescents with not well-controlled asthma after 3 months, but not after 12 months. Pediatr Pulmonol. 2012; 47:1170–1179. © 2012 Wiley Periodicals, Inc.

Maternal smoking during pregnancy, prematurity and recurrent wheezing in early childhood.

Abstract: Background Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood.

Effect of amplitude and inspiratory time in a bench model of non-invasive HFOV through nasal prongs.

Abstract: Background and objectives Non-invasive high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed to combine the advantages of oscillatory pressure waveform and non-invasive interface. We studied the effect of oscillation amplitude and inspiratory time on the pressure transmission and tidal volume delivery through different nasal prongs. Methods In vitro mechanical study on a previously described bench model of nHFOV. The model was built connecting SM3100A tubings to a neonatal lung model, via two differently sized binasal prongs. A circuit with no nasal prongs was used as control. Tidal volume (Tv), oscillatory pressure ratio (ΔPdist/ΔPprox), and ventilation (DCO2) were measured across a range of amplitudes and inspiratory times (IT). Measurements were performed with a low-dead space hot wire anemometer coupled with a pressure transducer. Results Using both nasal prongs, Tv, ΔPdist/ΔPprox, and DCO2 were 83%, 40%, and 71%, respectively, of those provided with the control circuit. No differences were noticed between small and large prongs. Tv and ΔPprox were linked by a quadratic relationship. Tv plateaus for amplitude values >65 cmH2O. ΔPdist/ΔPprox shows same tendency. Same results were obtained with both types of prongs and with increasing IT. On the whole, mean Tv was higher with IT at 50% than at 33% (2.4 ml vs. 1.4 ml; P < 0.001). Conclusions Changing oscillation amplitude and IT has a significant effect on ventilation. Varying these two parameters provides a theoretical Tv within the ideal values for HFOV also using the smallest nasal prongs. Pediatr Pulmonol. 2012. 47:1012–1018. © 2012 Wiley Periodicals, Inc.