Exercise as airway clearance therapy (ExACT) in cystic fibrosis: a UK-based e-Delphi survey of patients, caregivers and health professionals.

Replacing traditional airway clearance therapy (tACT) with exercise (ExACT) in people with cystic fibrosis (pwCF) is a top research priority. A UK-based e-Delphi consensus was performed to inform the type(s), duration and intensity of ExACT. The expert panel comprised CF physiotherapists, doctors, pwCF and parents/partners. Exercise ACT was considered to be aerobic activity, of at least 20 min duration and intense enough to elicit deep breathing. Consensus was reached that assessment breaths, coughs and huffs should accompany exercise to remove loose secretions, with support for trials to investigate ExACT versus tACT during times of stable disease but not pulmonary exacerbations.

Once daily combined inhaled steroid and ultra long-acting bronchodilator prescribing in pediatric asthma: a dual Center retrospective cohort study.

OBJECTIVE: A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted. METHODS: The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population. RESULTS: In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden. CONCLUSIONS: A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy.

STUDY OBJECTIVES: Epilepsy and obstructive sleep apnea syndrome (OSAS) are each relatively common in children. OSAS may affect cognition, such that recognition of OSAS is important for children and young people with epilepsy (CYPWE). Published pilot data reported 55% of CYPWE had symptoms suggestive of OSAS, compared with 7% of typically developing controls. The primary aim of this study was to ascertain OSAS prevalence by polysomnography in CYPWE, with secondary aims being to evaluate the utility of sleep questionnaires in CYPWE. METHODS: CYPWE and age- and sex-matched typically developing controls were studied. A single night of level I attended polysomnography was undertaken, along with questionnaires (Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire, Pittsburgh Sleep Quality Index, and the childhood and adolescent Epworth Sleepiness Scale). OSAS was defined as obstructive apnea-hypopnea index of ≥ 1 event/h. RESULTS: Polysomnography was performed in 72 children including 48 CYPWE (60% male) and 24 controls (54% male). Mean age (11 years) was similar for CYPWE and controls (P = .42), with slightly higher body mass index z scores (0.7 vs 0.1, P = .03) noted in CYPWE. Mean obstructive apnea-hypopnea index was 0.61 in CYPWE vs 0.42 in controls (P = .62). Despite higher Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire scores in CYPWE (0.38 vs 0.12, P < .001), no difference in OSAS prevalence (10% vs 4%, P = .78) was found. CYPWE had higher childhood and adolescent Epworth Sleepiness Scale (6 vs 3.5, P = .01) and Pittsburgh Sleep Quality Index (5 vs 3.3, P = .02) scores, indicating greater levels of daytime sleepiness and poorer sleep quality. CONCLUSIONS: The study found no evidence for increased OSAS prevalence in CYPWE, and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in predicting OSAS appears limited for CYPWE. CYPWE are, however, demonstrably sleepier and have poorer sleep quality. The cause for these findings remains unclear. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Investigation of Sleep Quality and Prevalence of Sleep-disordered Breathing in Children and Young People With Epilepsy; URL: https://www.clinicaltrials.gov/study/NCT03103841; Identifier: NCT03103841. CITATION: Urquhart DS, McLellan AE, Hill LE, et al. A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy. J Clin Sleep Med. 2024;20(7):1039-1047.

Epidemiology of Robin sequence in the UK and Ireland: an active surveillance study.

BACKGROUND: Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000-14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth. OBJECTIVES: To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment. METHODS: Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points. RESULTS: 173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone. CONCLUSIONS: Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence.

Application of Machine Learning to Optimize Management of Children in Hospital with Lower Respiratory Tract Infection.

Effective triage can help optimize the use of limited healthcare resources for managing paediatric patients with lower respiratory tract infection (LRTI), the primary cause of death worldwide for under 5 years old children. However, triage decisions do not consider medium to long term needs of hospitalized children. In this study, we aim to leverage data-driven methods using objective measures to predict the type of hospital stay (short or long). We used vital signs (heart rate, oxygen saturation, breathing rate, and temperature) recorded from 12,881 children admitted to paediatric intensive care units in China. We generated multiple features from each vital sign, and then used regularized logistic regression with 10-fold cross validation to test the generalizability of our models. We investigated the minimum number of recording days needed to provide a reliable estimate. We assessed model performance with Area Under the Curve (AUC) using Receiver Operating Characteristic. Our results show that each vital sign independently helps predict hospital stay and the AUC increases further when vital signs are combined. In addition, early prediction of the type of stay of a patient admitted for LRTI using vital signs is possible, even with using only one day of recordings. There is now a need to apply these predictive models to other populations to assess the generalizability of the proposed methods.

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study.

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016-2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016-2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.

Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study.

BACKGROUND: Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity. METHODS: A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without. RESULTS: 12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03). CONCLUSIONS: These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF.

A Case of "Abnormally Abnormal" Hypoxic Ventilatory Responses: A Novel NPARM PHOX 2B Gene Mutation.

ABSTRACT: Congenital central hypoventilation syndrome (CCHS) is a rare disorder associated with dysregulation of the autonomic ventilatory response to hypoxia and hypercarbia usually caused by polyalanine repeat expansion mutations in the PHOX 2B gene. Non-polyalanine repeat mutations (NPARM) represent approximately 10% of cases, and usually require continuous ventilation during sleep, although our knowledge of disease progression is limited. Here we present a case with a novel NPARM CCHS mutation associated with a premature stop codon for the PHOX 2B protein. Despite the type of the mutation, patient management with supplementary oxygen has been sufficient. Experience from our case may help when counseling parents.

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis.

INTRODUCTION: Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. MATERIALS AND METHODS: DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. RESULTS: 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean +/- SEM rates of change of %predicted FEV(1)/year (0.9 +/- 2.3 (DD) vs. - 3.9 +/- 2.8 (DG), p = 0.22), %predicted FEV(1) (76 +/- 8 vs. 74 +/- 11), p = 0.91), or z scores for height ( - 0.47 +/- 0.26 vs. - 0.24 +/- 0.19, p = 0.48) and weight ( - 0.01 +/- 0.22 vs. - 0.29 +/- 0.27, p = 0.44). Median +/- SE survival age at first PA isolation was also not significantly different (3.5 +/- 2.1 vs. 6.5 +/- 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. CONCLUSIONS: Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.

Deaths in childhood from cystic fibrosis: 10-year analysis from two London specialist centres.

INTRODUCTION: Death in childhood from cystic fibrosis (CF) is now an uncommon event in the U.K. We wished to assess the circumstances surrounding deaths (and lung transplantation) in the modern era of CF care. METHODS: A retrospective review was carried out pooling data from two large paediatric specialist CF units in London for the 10-year period 2000-2009 inclusive. RESULTS: There were 11 deaths and eight children who had a lung transplant out of 1022 children cared for in this period. Median age of death was 14.2 years and transplant 13.0 years, with a female preponderance (82% deaths and 75% transplants). Apart from one child (forced expiratory volume in 1 s (FEV1) 69%), lung function indicated severe lung disease (median FEV1 33%, range 12%-69%). Values 5 years prior to death were not predictive (median FEV1 62%, range 32%-96%), and those 1 year prior were similar to the last recorded levels. Almost all (10/11) died in hospital and 5/11 (45%) were ventilated. Respiratory failure was the commonest mode of death (64%). Only four children (36%) were receiving palliative care, and in six cases (55%) care was withdrawn. CONCLUSIONS: The number of deaths in children with CF was small but often unpredictable, so active management was continued until late in the majority, reflected by the fact that almost all were in hospital, and more than half were ventilated. If death from respiratory failure is anticipated following a steady decline, palliative care should be instituted well in advance, with attention to appropriate end of life care.

Effects of a supervised, outpatient exercise and physiotherapy programme in children with cystic fibrosis.

Previous work suggests benefit from outpatient exercise and physiotherapy in children with cystic fibrosis (CF), namely improved exercise capacity and lung function measures, as well reduced intravenous (IV) antibiotic needs. Our study aim was to investigate the effect of a year-long supervised outpatient exercise and physiotherapy programme in children with CF. Subjects with CF aged ≥10 years who had received ≥4 courses of IV antibiotics in 2009 were enrolled and seen fortnightly for supervised exercise and physiotherapy throughout 2010. In addition, they were expected to exercise three times weekly, and if unwell complete additional physiotherapy sessions extra to usual chest physiotherapy. Assessments of exercise capacity using the Modified Shuttle Test (MST) and quality of life (QOL; CFQ-UK) were recorded at baseline and after 1 year. Regular spirometry was performed before and throughout the study. Data were collected on IV antibiotic days. 12 subjects (6 female) were enrolled with mean (95% CI) age of 13.3 (11.8-14.6) years at study entry. A significant reduction in IV antibiotic days from 60 (56-64) days in 2009 to 50 (44-56) in 2010 (P = 0.02) was noted, along with improved MST distance (m) [735 (603-867) vs. 943 (725-1,161), P = 0.04] and level attained [9.4 (8.4-10.5) vs. 11.1 (9.6-12.6), P = 0.04]. Significant improvements in CFQ-UK scores for physical [59 (47-72) vs. 83 (74-92), P = 0.001], emotional [63 (55-72) vs. 84 (74-93), P < 0.001], treatment [41 (30-51) vs. 61 (48-73), P = 0.002], and respiratory [54 (42-66) vs. 76 (70-82), P = 0.002] domains were noted. The mean (95% CI) rate of change of FEV(1) was -4 (-18, +10)% in 2009, but was +6 (-2, +13)% in 2010, although this did not reach statistical significance. Supervised, outpatient exercise and physiotherapy are associated with improvements in QOL and exercise tolerance, a reduction in IV antibiotic days, and a trend towards reducing lung function decline in children with CF. The cost of IV antibiotics was reduced by £66,384 ($104,000) in 2010 when compared with 2009. Such cost-benefit may have implications for workforce planning and service provision.

Blurring the lines in interferon {gamma} receptor deficiency: an infant with near-fatal airway disease.

Deficiencies of the interferon γ (IFN-γ) pathway have become a well-recognized cause of nontuberculous mycobacterial infection. We report here a case of autosomal dominant IFN-γ receptor 1 (IFN-γ-R1) deficiency presenting at the unusually young age of 16 months with a severe clinical course. Mycobacterium avium complex was cultured from bronchial washings of a child who presented with primary endobronchial disease after a 4-month history of rhinorrhea, wheeze, and acute lobar consolidation. A maternal history of multifocal Mycobacterium kansasii osteomyelitis and cutaneous M avium complex led to genetic confirmation of IFN-γ-R1 818del4 deletion (a 4 base pair deletion at nucleotide position 818) in both family members. This case demonstrates the link between mycobacterial disease and IFN-γ pathway deficiency, the diagnosis of which facilitates more accurate therapy and genetic counseling. The case also raises questions about the reported distinct presentation, treatment, and prognosis of autosomal dominant and recessive IFN-γ-R1 phenotypes.

Fungal pleural effusion secondary to a rare cause of pancreatic pseudocyst.

We report a case of fungal pleural effusion secondary to presumed valproate induced pancreatitis with pseudocyst and stricture formation. A child with dyskinetic cerebral palsy who had been on sodium valproate for several years was transferred for drainage of a left sided pleural effusion. Pleural fluid culture consistently grew Candida glabrata although the patient was treated with broad-spectrum antibiotic and antifungal therapy. Clinical deterioration ensued with abdominal discomfort, feed intolerance, and re-accumulation of the effusion. Investigations revealed a large pancreatic pseudocyst compressing the stomach and impairing pancreatic function. Subsequent therapeutic evacuation of pancreatic fluid demonstrated C. glabrata. This case underscores that pleural disease may be secondary to abdominal pathology, and always to consider rare side-effects of medication in the face of a puzzling clinical picture.