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.

Caregiver Burden Due to Pulmonary Exacerbations in Patients with Cystic Fibrosis.

OBJECTIVE: To describe the poorly understood burden of pulmonary exacerbations experienced by primary caregivers of children (aged 2-17 years) with cystic fibrosis (CF), who frequently require prolonged hospitalizations for treatment of pulmonary exacerbations with intravenous (IV) antibiotics. STUDY DESIGN: In this prospective observational study, 88 caregivers in Germany, Ireland, the United Kingdom, and the US completed a survey during pulmonary exacerbation-related hospitalizations (T1) and after return to a "well state" of health (T2). The impact of pulmonary exacerbations on caregiver-reported productivity, mental/physical health, and social/family/emotional functioning was quantified. RESULTS: Primary caregivers of children with CF reported significantly increased burden during pulmonary exacerbations, as measured by the 12-item Short-Form Health Survey mental health component and the Work Productivity and Activity Impairment: Specific Health Problem absenteeism, presenteeism, work productivity loss, and activity impairment component scores. Compared to the "well state," during pulmonary exacerbations-related hospitalization caregivers reported lower physical health scores on the Child Health Questionnaire-Parent Form 28. Quality-of-life scores on the Caregiver Quality of Life Cystic Fibrosis scale and total support score on the Multidimensional Scale of Perceived Social Support did not differ significantly between T1 and T2. More caregivers reported a negative impact on family/social/emotional functioning during pulmonary exacerbations than during the "well state." CONCLUSIONS: Pulmonary exacerbations necessitating hospitalization impose a significant burden on primary caregivers of children with CF. Preventing pulmonary exacerbations may substantially reduce this burden.

A review of filamin A mutations and associated interstitial lung disease.

The filamin A gene (FLNA) on Xq28 encodes the filamin A protein. Mutation in FLNA causes a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, intellectual disability and intestinal obstruction. Recently, childhood-onset interstitial lung disease associated with a range of FLNA mutations has been recognised and reported. We document our personal experience of this emerging disorder and compile a comprehensive overview of clinical features and molecular changes in all identifiable published cases. Reviewing the emerging dataset, we underline this unanticipated phenotypic consequence of pathogenic FLNA mutation-associated pulmonary disease.Conclusion: From the emerging data, we suggest that while reviewing complex cases with a sustained oxygen requirement against a clincial background of cardiac concerns or intestinal obstruction to have a high index of suspicion for FLNA related pathology and to instigate early MRI brain scan and FLNA mutation analysis. What is Known: • FLNA gene on Xq28 encodes the filamin A protein and mutation therein is associated with variable phenotypes depending on its nature of mutation. • Loss-of-function mutation of filamin A is associated with X-linked inherited form of periventricular nodular heterotopia with or without epilepsy with most individuals affected being female. There is a recently recognised associated respiratory phenotype. What is New: • The respiratory phenotype in the form of childhood interstitial lung disease is a recently recognised clinical consequence of loss-of-function FLNA mutation. • Rare male patients with loss-of-function FLNA mutation-associated lung disease with residual protein function can survive into infancy with a severe form of the phenotype.

Longitudinal assessment of airway responsiveness from 1 month to 18 years in the PIAF birth cohort.

The Perth Infant Asthma Follow-up (PIAF) study involves a birth cohort of unselected subjects who have undergone longitudinal assessments of airway responsiveness at 1, 6 and 12 months and 6, 11 and 18 years of age. The aim of this study was to determine the relationship between increased airway responsiveness throughout childhood and asthma in early adult life.Airway responsiveness to histamine, assessed as a dose-response slope (DRS), and a respiratory questionnaire were completed at 1, 6 and 12 months and 6, 11 and 18 years of age.253 children were initially recruited and studied. Airway responsiveness was assessed in 203, 174, 147, 103, 176 and 137 children at the above-mentioned time points, respectively (39 participants being assessed on all test occasions). Asthma at 18 years was associated with increased airway responsiveness at 6, 12 and 18 years, but not during infancy (slope 0.24, 95% CI 0.06-0.42; p=0.01; slope 0.25, 95% CI 0.08-0.49; p=0.006; and slope 0.56, 95% CI 0.29-0.83; p<0.001, respectively).Increased airway responsiveness and its association with asthma at age 18 years is established between infancy and 6 years. We propose that airway responsiveness in early life reflects the initial airway geometry and airway responsiveness later in childhood increasingly reflects immunological responses to environmental influences.

Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions.

RATIONALE: Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined. OBJECTIVES: To determine whether acute wheezing exacerbations due to HRV-C are associated with increased hospital attendances due to acute respiratory illnesses (ARIs). METHODS: Clinical information and nasal samples were collected prospectively from 197 children less than 5 years of age, presenting to hospital with an acute wheezing episode. Information on hospital attendances with an ARI before and after recruitment was subsequently obtained. MEASUREMENTS AND MAIN RESULTS: HRV was the most common virus identified at recruitment (n = 135 [68.5%]). From the 120 (88.9%) samples that underwent typing, HRV-C was the most common HRV species identified, present in 81 (67.5%) samples. Children with an HRV-related wheezing illness had an increased risk of readmission with an ARI (relative risk, 3.44; 95% confidence interval, 1.17-10.17; P = 0.03) compared with those infected with any other virus. HRV-C, compared with any other virus, was associated with an increased risk of a respiratory hospital admission before (49.4% vs. 27.3%, respectively; P = 0.004) and within 12 months (34.6% vs. 17.0%; P = 0.01) of recruitment. Risk for subsequent ARI admissions was further increased in atopic subjects (relative risk, 6.82; 95% confidence interval, 2.16-21.55; P = 0.001). Admission risks were not increased for other HRV species. CONCLUSIONS: HRV-C-related wheezing illnesses were associated with an increased risk of prior and subsequent hospital respiratory admissions. These associations are consistent with HRV-C causing recurrent severe wheezing illnesses in children who are more susceptible to ARIs.

Characterization of maximal respiratory pressures in healthy children.

BACKGROUND: Measurements of maximal voluntary inspiratory (PI(max)) and expiratory (PE(max)) pressures are used in the management of respiratory muscle disease. There is little data on the appropriate reference range, success rates, or repeatability of PI(max) and PE(max) in children or on methodological factors affecting test outcomes. OBJECTIVES: To determine PI(max) and PE(max) in healthy children and examine which published reference equations are best suited to a contemporary population. Secondary objectives were to assess within-test repeatability and the influence of lung volumes on PI(max) and PE(max). METHODS: Healthy children were prospectively recruited from the community on a volunteer basis and underwent spirometry, static lung volumes, and PI(max) and PE(max) testing. RESULTS: Acceptable and repeatable (to within 20%) PI(max) and PE(max) were obtained in 156 children, with 105 (67%) children performing both PI(max) and PE(max) measurements to within 10% repeatability. The reference equations of Wilson et al. [Thorax 1984;39:535-538] best matched our healthy Caucasian children. There was an inverse relationship between PI(max) and the percent of total lung capacity (TLC) at which the measurement was obtained (beta coefficient -0.96; 95% CI -1.52 to -0.39; p = 0.001), whereas at lung volumes of >80% TLC PE(max) was independent of lung volume (p = 0.26). CONCLUSION: We demonstrated that the Wilson et al. [Thorax 1984;39:535-538] reference ranges are most suited for contemporary Caucasian Australasian children. However, robust multiethnic reference equations for maximal respiratory pressures are required. This study suggests that 10% within-test repeatability criteria are feasible in clinical practice, and that the use of lung volume measurements will improve the quality of maximal respiratory pressure measurements.