Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

BACKGROUND: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. OBJECTIVE: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. METHODS: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. RESULTS: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. CONCLUSION: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Increased airway smooth muscle in preschool wheezers who have asthma at school age.

BACKGROUND: Increased airway smooth muscle (ASM) is a feature of established asthma in schoolchildren, but nothing is known about ASM in preschool wheezers. OBJECTIVE: We sought to determine endobronchial biopsy specimen ASM area fraction in preschool wheezers and its association with asthma at school age. METHODS: ASM area, reticular basement membrane thickness, and mucosal eosinophil and ASM mast cell values were quantified in endobronchial biopsy specimens previously obtained from preschool children undergoing clinically indicated bronchoscopy: severe recurrent wheezers (n=47; median age, 26 months) and nonwheezing control subjects (n=21; median age, 15 months). Children were followed up, and asthma status was established at age 6 to 11 years. Preschool airway pathology was examined in relation to asthma at school age. RESULTS: Forty-two (62%) of 68 children had 1 or more evaluable biopsy specimens for ASM. At school age, 51 of 68 children were followed up, and 15 (40%) of 37 preschool wheezers had asthma. Children who had asthma and an evaluable biopsy specimen had increased preschool ASM area fraction (n=8; median age, 8.2 years [range, 6-10.4 years]; median ASM, 0.12 [range, 0.08-0.16]) compared with that seen in children without asthma (n=24; median age, 7.3 years [range, 5.9-11 years]; median ASM, 0.07 [range, 0.02-0.23]; P=.007). However, preschool reticular basement membrane thickness and mucosal eosinophil or ASM mast cell values were not different between those who did or did not have asthma at school age. CONCLUSION: Increased preschool ASM is associated with those children who have asthma at school age. Thus a focus on early changes in ASM might be important in understanding the subsequent development of childhood asthma.

Universal Design in Education (UDE) Across the Life Course: Applying a Systems Framework to Create an Inclusive Experience for All.

The UN Convention on the Rights of Persons with Disabilities (UNCRPD) promotes the realisation of the right of persons with disabilities to education through Article 24 - Education. Universal Design in Education (UDE) fosters a whole systems approach so that the physical and digital environments, the educational services, and the teaching and learning can be easily accessed, understood and used, by the widest range of learners and by all key stakeholders, in a more inclusive environment. The whole systems approach incorporates the entire educational environment, as well as the recognition of the capacity for all learners (including persons with disabilities) to learn, and environments which are fully accessible and inclusive. This paper discusses methods whereby a systems approach can be applied to various aspects of education across the life continuum. It further advocates the inclusion of Universal Design as subject matter in curricula and assessment, to ensure a broader and more widespread adoption across the educational spectrum.

Efficacy and adherence of noninvasive ventilation treatment in children with Down syndrome.

OBJECTIVE: Children with Down syndrome (DS) have an increased prevalence of obstructive sleep apnea (OSA). Noninvasive ventilation (NIV) is a common modality of OSA treatment in this cohort. This study aimed to measure adherence and efficiency of NIV delivery in children with DS. STUDY DESIGN: This was a retrospective cohort study involving 106 children with confirmed OSA and home NIV with downloadable data capacity. Children were divided into DS (n = 44) and non-DS cohorts (n = 62). Adherence, clinical outcomes apnea-hypopnoea index (AHI), positive airway pressure delivery, and leakage were recorded and compared between DS and non-DS cohorts and within the DS cohort based on past surgical history. RESULTS: Significantly greater NIV usage was observed in the DS cohort, they showed more consistent use with an increased percentage of days used relative to their non-DS counterparts (78.95 ± 2.26 vs. 72.11 ± 2.14, p = .031). However, despite greater usage, poorer clinical outcomes in the form of increased AHI (p = .0493) was observed in the DS cohort, where significantly greater leakage was also shown 41.00 ± 1.61 L/min versus 36.52 ± 1.18 L/min (p = .022). Twenty children with DS had prior cardiac surgery; compliance across all parameters was significantly reduced relative to those without. CONCLUSION: These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS.

Pediatric invasive long-term ventilation-A 10-year review.

INTRODUCTION: The number of children with complex physical and developmental pathologies, including chronic respiratory insufficiency, surviving and growing beyond early childhood continues to rise. No study has examined the clinical pathway of children on invasive long-term mechanical ventilation (LTMV) in an Irish setting. Our data over a 10-year period were reviewed to see if our demographics and outcomes are in line with global trends. METHODS: Children's Health Ireland (CHI) at Crumlin, Dublin is Ireland's largest tertiary pediatric hospital. A retrospective review analyzed data from children in our center commenced on LTMV via a tracheostomy over 10 years (2009-2018). This data was subdivided into two epochs for statistical analysis of longitudinal trends. RESULTS: Forty-six children were commenced on LTMV from 2009 to 2018. Many had complex medical diagnoses with associated comorbidities. Far less children, 30.4% (n = 14) commenced LTMV in the latter half of the 10-year period, they also fared better in all aspects of their treatment course. Focusing solely on children who have needed LTMV over this timeframe we have been able to isolate trends specific to this cohort. Less patients commenced LTMV on a year-on-year basis, and for those that require tracheostomy and LTMV, their journey to decannulation tends to be shorter. CONCLUSION: Over the period reviewed, less patients over time necessitated LTMV, and those patients are being weaned and decannulated with ever more success. This has implications in terms of predicting numbers transitioning to adult services and allocation of hospital and community care resources.

Diffuse lung disease in infants less than 1 year of age: Histopathological diagnoses and clinical outcome.

INTRODUCTION: Interstitial lung disease (ILD) in infants is rare. Clinical and radiological features are often non-specific, and overlap with growth disorders and infection. In infants with severe respiratory compromise, lung biopsy is often necessary to guide acute management, but the risk and diagnostic yield of this procedure is incompletely understood. AIMS: To retrospectively review infants undergoing open lung biopsy for suspected ILD at a large referral center; to determine morbidity and mortality related to the procedure; and to describe subsequent diagnosis and outcome. METHODS: Lung biopsies performed in infants (aged <1 year) between January 1, 2005 and March 31, 2012 were identified and clinical data were collected. Biopsies were reclassified using the ChILD classification for diffuse lung disorders in infants. RESULTS: Twenty-seven infants were identified, with the number of biopsies performed increasing each year over the study period. There was no mortality and negligible morbidity associated with biopsy. Diagnoses seen were similar to those reported by the ChILD network. Histopathological diagnosis was not compatible with life in the absence of lung transplant in 6/27 (22%) of infants. Of the 14 children longitudinally followed up (median 0.5 (0.4 - 5.81) years), only four continued to require supplemental oxygen. CONCLUSION: Lung biopsy in infants with suspected ILD is safe, and histopathological diagnosis frequently assists treatment decisions, particularly with regard to withdrawal of care.

Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis.

Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment.