Intra- and Inter-rater Agreement of Superior Vena Cava Flow and Right Ventricular Outflow Measurements in Late Preterm and Term Neonates.

OBJECTIVES: To explore the intra- and inter-rater agreement of superior vena cava (SVC) flow and right ventricular (RV) outflow in healthy and unwell late preterm neonates (33-37 weeks' gestational age), term neonates (≥37 weeks' gestational age), and neonates receiving total-body cooling. METHODS: The intra- and inter-rater agreement (n = 25 and 41 neonates, respectively) rates for SVC flow and RV outflow were determined by echocardiography in healthy and unwell late preterm and term neonates with the use of Bland-Altman plots, the repeatability coefficient, the repeatability index, and intraclass correlation coefficients. RESULTS: The intra-rater repeatability index values were 41% for SVC flow and 31% for RV outflow, with intraclass correlation coefficients indicating good agreement for both measures. The inter-rater repeatability index values for SVC flow and RV outflow were 63% and 51%, respectively, with intraclass correlation coefficients indicating moderate agreement for both measures. CONCLUSIONS: If SVC flow or RV outflow is used in the hemodynamic treatment of neonates, sequential measurements should ideally be performed by the same clinician to reduce potential variability.

How many paediatric referrals to an allergist could be managed by a general practitioner with special interest?

BACKGROUND: The concept of a general practitioner with special interest (GPwSI) was first proposed in the 2000 National Health Service Plan, as a way of providing specialized treatment closer to the patient's home and reducing hospital waiting times. Given the patchy and inadequate provision of paediatric allergy services in the UK, the introduction of GPwSIs might reduce pressure on existing specialist services. METHODS: A total of 100 consecutive referrals to a specialist paediatric allergy clinic were reviewed to assess what proportion could be managed by a GPwSI allergy service with a predefined range of facilities and expertise (accurate diagnosis and management of allergy; skin prick testing; provision of allergen avoidance advice; ability to assess suitability for desensitization). Each referral was reviewed independently by three allergy specialists. Cases were initially judged on the referral letter and then, to determine whether appropriate triage decisions could be made prospectively, cases were re-assessed with information summarized in the clinic letter. The proportion of referrals suitable for a GPwSI was calculated and their characteristics identified. RESULTS: At least 42% and up to 75% were suitable for management by a GPwSI in allergy based on unanimous and majority agreement, respectively. The appropriateness of 79% referrals could be identified based on the information in the referral letter. A total of 19% referrals were unsuitable for a GPwSI service because of complex or multisystem disease, need for specialist knowledge or facilities or patient's young age. CONCLUSIONS: At least two-fifths of paediatric allergy referrals to our hospital-based service could be dealt with in a GPwSI clinic, thereby diversifying the patient pathway, allowing specialist services to focus on complex cases and reducing waiting times for appointments.

Options for assessing and measuring chest wall motion.

Assessing chest wall motion is a basic and vital component in managing the child with respiratory problems, whether these are due to pathology in the lungs, airways, chest wall or muscles. Since the 1960s, clinical assessment has been supplemented with an ever-growing range of technological options for measuring chest wall motion, each with unique advantages and disadvantages. Measurements of chest wall motion can be used to: (1) Assess respiratory airflow and volume change, as a non-invasive alternative to measurement at the airway opening, (2) Monitor breathing over long periods of time, to identify apnoea and other types of sleep-disordered breathing, (3)Identify and quantify patterns of abnormal chest wall movement, whether between ribcage and abdominal components (thoracoabdominal asynchrony) or between different regions of the ribcage (eg in scoliosis and pectus excavatum). Measuring chest wall motion allows us to do things which simply cannot be done by more mainstream respiratory function techniques measuring flow at the airway opening: it allows respiratory airflow to be measured when it would otherwise be impossible, and it tells us how the different parts of the chest wall (eg ribcage vs abdomen, right vs left) are moving in order to generate that airflow. The basis of the different techniques available to assess and measure chest wall motion will be reviewed and compared, and their relevance to paediatric respiratory practice assessed.

Visible damp in a child's bedroom is associated with increased respiratory morbidity in early life: a multicentre cohort study.

OBJECTIVE: Household damp exposure is an important public health issue. We aimed to assess the impact of the location of household damp on respiratory outcomes during early life. METHODS: Household damp exposure was ascertained in children recruited to the GO-CHILD multicentre birth cohort study. The frequency of respiratory symptoms, infections, healthcare utilisation and medication prescription for wheezing were collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained in 1344 children between August 2010 and January 2016. Visible damp was present in a quarter of households (25.3%) with 1 in 12 children's bedrooms affected (8.3%). Damp in the bathroom, kitchen or living room was not associated with any respiratory or infection-related outcomes. Damp in the child's bedroom was associated with an increased risk of dry cough (8.7% vs 5.7%) (adjusted relative risk 1.56, 95% CI 1.07 to 2.27; p=0.021) and odds of primary care attendance for cough and wheeze (7.6% vs 4.4%) (adjusted OR 1.37, 95% CI 1.07 to 1.76; p=0.009). There were also increased risk of inhaled corticosteroid (13.3% vs 5.9%) (adjusted RR 2.22, 95% CI 1.04 to 4.74; p=0.038) and reliever inhaler (8.3% vs 5.8%) (adjusted RR 2.01, 95% CI 1.21 to 2.79; p=0.018) prescription. CONCLUSION: Damp in the child's bedroom was associated with increased respiratory morbidity. In children presenting with recurrent respiratory symptoms, clinicians should enquire about both the existence and location of damp, the presence of which can help prioritise those families requiring urgent household damp assessment and remediation works.

High-Flow Humidified Oxygen as an Early Intervention in Children With Acute Severe Asthma: Protocol for a Feasibility Randomized Controlled Trial.

BACKGROUND: Acute severe asthma (ASA) is a leading cause of hospital attendance in children. Standard first-line therapy consists of high-dose inhaled bronchodilators plus oral corticosteroids. Treatment for children who fail to respond to first-line therapy is problematic: the use of intravenous agents is inconsistent, and side effects are frequent. High-flow humidified oxygen (HiFlo) is widely used in respiratory conditions and is increasingly being used in ASA, but with little evidence for its effectiveness. A well-designed, adequately powered randomized controlled trial (RCT) of HiFlo therapy in ASA is urgently needed, and feasibility data are required to plan such an RCT. In this study, we describe the protocol for a feasibility study designed to fill this knowledge gap. OBJECTIVE: This study aims to establish whether a full RCT of early HiFlo therapy in children with ASA can be conducted successfully and safely, to establish whether recruitment using deferred consent is practicable, and to define appropriate outcome measures and sample sizes for a definitive RCT. The underlying hypothesis is that early HiFlo therapy in ASA will reduce the need for more invasive treatments, allow faster recovery and discharge from hospital, and in both these ways reduce distress to children and their families. METHODS: We conducted a feasibility RCT with deferred consent to assess the use of early HiFlo therapy in children aged 2 to 11 years with acute severe wheeze not responding to burst therapy (ie, high-dose inhaled salbutamol with or without ipratropium). Children with a Preschool Respiratory Assessment Measure score ≥5 after burst therapy were randomized to commence HiFlo therapy or follow standard care. The candidate primary outcomes assessed were treatment failure requiring escalation and time to meet hospital discharge criteria. Patient and parent experiences were also assessed using questionnaires and telephone interviews. RESULTS: The trial was opened to recruitment in February 2020 but was paused for 15 months owing to the COVID-19 pandemic. The trial was reopened at the lead site in July 2021 and opened at the other 3 sites from August to December 2022. Recruitment was completed in June 2023. CONCLUSIONS: This feasibility RCT of early HiFlo therapy in children with ASA recruited to the target despite major disturbances owing to the COVID-19 pandemic. The data are currently being analyzed and will be published separately. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry ISRCTN78297040; https://www.isrctn.com/ISRCTN78297040. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54081.

Environmental risk factors for respiratory infection and wheeze in young children: A multicentre birth cohort study.

INTRODUCTION: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood. METHODS: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29). CONCLUSION: Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children.

Prevalence of nontuberculous mycobacteria in cystic fibrosis clinics, United Kingdom, 2009.

Incidence of pulmonary infection with nontuberculous mycobacteria (NTM) is increasing among persons with cystic fibrosis (CF). We assessed prevalence and management in CF centers in the United Kingdom and found 5.0% of 3,805 adults and 3.3% of 3,317 children had recently been diagnosed with NTM. Of those, 44% of adults and 47% of children received treatment.

Bronchodilator response by interrupter technique to guide management of preschool wheeze.

OBJECTIVE: We examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit from ICS. DESIGN: Clinical non-randomised intervention study SETTING: Secondary care. PATIENTS: Preschool children (2 years to <6 years) with recurrent wheeze. INTERVENTIONS: Inhaled beta-agonist, ICS. OUTCOME MEASURES: We measured prebronchodilator and postbronchodilator interrupter resistance (Rint) and symptom scores at 0 (V1), 4 (V2) and 12 (V3) weeks. At V2, those with a predetermined symptom level commenced ICS. Modified Asthma Predictive Index (mAPI) and parental perception of response to bronchodilator were recorded. Response to ICS was defined as a reduction in daily symptom score of >0.26. Positive BDR was defined as fall in Rint of ≥0.26 kPa.s/L, ≥35% predicted or ≥1.25 Z Scores. RESULTS: Out of 138 recruited children, 67 completed the full study. Mean (SD) prebronchodilator Rint at V2 was 1.22 (0.35) kPa.s/L, and fell after starting ICS (V3) to 1.09 (0.33) kPa.s/L (p<0.001), while mean (SD) daily symptom score fell from 0.56 (0.36) to 0.28 (0.36) after ICS (p<0.001). Positive Rint BDR before ICS (at V1 and/or V2), using all three threshold criteria, was significantly associated with response to ICS on symptom scores at V3 (p<0.05). mAPI was not significantly associated with response to ICS, and parents' perception of response to bronchodilator was not related to measured Rint BDR . CONCLUSIONS: Rint BDR may be helpful in selecting which wheezy preschool children are likely to benefit from ICS.

Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: Results from the CLIMB-CF study.

BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.

Definitions of non-response and response to biological therapy for severe asthma: a systematic review.

Background: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. Methods: We searched four bibliographic databases from inception to 15 March 2021. Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. Results: 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards. Conclusions: This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Pulse oximetry respiratory monitoring for assessment of acute childhood wheeze.

OBJECTIVE: There is a lack of objective measures to assess children with acute wheezing episodes. Increased respiratory rate (RR) and pulsus paradoxus (PP) are recognised markers, but poorly recorded in practice. We examined whether they can be reliably assessed from a pulse oximeter plethysmogram ('pleth') trace and predict clinical outcome. PATIENTS AND METHODS: We studied 44 children aged 1-7 years attending hospital with acute wheeze, following initial 'burst' bronchodilator therapy (BT), and used custom software to measure RR and assess PP from oximeter pleth traces. Traces were examined for quality, and the accuracy of the RR measurement was validated against simultaneous respiratory inductive plethysmography (RIP). RR and PP at 1 hour after BT were compared with clinical outcomes. RESULTS: RR from pleth and RIP showed excellent agreement, with a mean difference (RIP minus pleth) of -0.5 breaths per minute (limits of agreement -3.4 to +2.3). 52% of 1 min epochs contained 10 s or more of pleth artefact. At 1 hour after BT, children who subsequently required intravenous bronchodilators had significantly higher RR (median (IQR) 63 (62-66) vs 43 (37-51) breaths per minute) than those who did not, but their heart rate and oxygen saturation were similar. Children with RR ≥55 per minute spent longer in hospital: median (IQR) 30 (22-45) vs 10 (7-21) hours. All children who subsequently required hospital admission had PP-analogous pleth waveforms 1 hour after BT. CONCLUSION: RR can be reliably measured and PP detected from the pulse oximeter pleth trace in children with acute wheeze and both markers predict clinical outcome. TRIAL REGISTRATION NUMBER: UKCRN15742.

A prospective cohort study using non-invasive methods of cardiovascular assessment to compare postnatal adaptation in well late preterm and term infants.

Echocardiography was combined with pulse oximetry plethysmography to investigate postnatal cardiovascular adaptation in late preterm and term infants. Median (IQR) pleth variability decreased over three days and similar, day2 15%(12-18%) preterm versus 16%(15-18%) term infants. Median (IQR) pulse transit time heart rate normalised was lower in term babies, day2 0.55(0.51-0.63) versus 0.64(0.62-0.68).

Non-invasive sensor methods used in monitoring newborn babies after birth, a clinical perspective.

BACKGROUND: Reducing the global new-born mortality is a paramount challenge for humanity. There are approximately 786,323 live births in the UK each year according to the office for National Statistics; around 10% of these newborn infants require assistance during this transition after birth. Each year around, globally around 2.5 million newborns die within their first month. The main causes are complications due to prematurity and during delivery. To act in a timely manner and prevent further damage, health professionals should rely on accurate monitoring of the main vital signs heart rate and respiratory rate. AIMS: To present a clinical perspective on innovative, non-invasive methods to monitor heart rate and respiratory rate in babies highlighting their advantages and limitations in comparison with well-established methods. METHODS: Using the data collected in our recently published systematic review we highlight the barriers and facilitators for the novel sensor devices in obtaining reliable heart rate measurements. Details about difficulties related to the application of sensors and interfaces, time to display, and user feedback are explored. We also provide a unique overview of using a non-invasive respiratory rate monitoring method by extracting RR from the pulse oximetry trace of newborn babies. RESULTS: Novel sensors to monitor heart rate offer the advantages of minimally obtrusive technologies but have limitations due to movement artefact, bad sensor coupling, intermittent measurement, and poor-quality recordings compared to gold standard well established methods. Respiratory rate can be derived accurately from pleth recordings in infants. CONCLUSION: Some limitations have been identified in current methods to monitor heart rate and respiratory rate in newborn babies. Novel minimally invasive sensors have advantages that may help clinical practice. Further research studies are needed to assess whether they are sufficiently accurate, practical, and reliable to be suitable for clinical use.

Mannose-binding lectin genotype is associated with respiratory disease in young children: A multicenter cohort study.

BACKGROUND: Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. METHODS: MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months. RESULTS: Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33-2.85) and pneumonia (RR 2.46, 95% CI 1.16-5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95% CI 1.04-1.43), emergency department attendance (RR 1.90 95% CI 1.13-3.19), and hospital admission (RR 2.01, 95% CI 1.04-3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95% CI 0.53-0.98). CONCLUSION: The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.

The association between parent's and healthcare professional's behavior and children's coping and distress during venepuncture.

OBJECTIVES: Examine the association between children's distress and coping during venepuncture with parent's and healthcare professional's behavior in a sample from the UK. METHODS: Fifty children aged 7-16 years accompanied by a carer were videotaped while having venepuncture. Verbalizations of children, parents, and healthcare professionals were coded using the Child-Adult Medical Procedure Interaction Scale-Revised. RESULTS: Children's distress was associated with child's age, anxiety, and distress promoting behavior of adults (R(2) = .91). Children's coping was associated with age, anxiety, and coping promoting behaviors of adults (R(2) = .57). Associations were stronger between healthcare professional's behavior and child coping; and between parent's behaviors and child distress. Empathizing, apologizing, and criticism were not frequently used by adults in this sample (<12%). CONCLUSION: This study supports and extends previous research showing adult's behavior is important in children's distress and coping during needle procedures. Clinical implications and methodological issues are discussed.

Adherence to treatment in adolescents with cystic fibrosis: the role of illness perceptions and treatment beliefs.

OBJECTIVES: This study was conducted to explore the relationships between illness perceptions, emotional representations, treatment beliefs and reported adherence in adolescents with cystic fibrosis (CF). METHODS: Thirty-eight adolescents completed questionnaires assessing their perceptions of CF, beliefs about prescribed treatments and reported adherence to chest physiotherapy, enzyme supplements, and antibiotics. RESULTS: Reported non-adherence to chest physiotherapy was associated with the way in which patients judged their personal need for treatment relative to their concerns about potential adverse effects. Patients reported strong doubts about the necessity of chest physiotherapy. Reported non-adherence to antibiotics was related to doubts about the necessity of antibiotics, believing that CF is not amenable to treatment control. Despite these beliefs about treatment, participants perceived CF as a chronic condition. CONCLUSIONS: The findings provide preliminary support for the self-regulatory model, using the necessity-concerns framework to operationalize treatment beliefs, in explaining adherence to treatment in adolescents with CF.

A management guideline to reduce the frequency of blood transfusion in very-low-birth-weight infants.

Very-low-birth-weight (VLBW) infants often require blood transfusions for anemia. Studies have investigated the preventative effect of delayed cord clamping, high-dose iron, and costly recombinant erythropoietin. As part of our unit clinical governance framework to improving patient care, we audited the effect of a preventative management guideline that combines delayed cord clamping for 30 seconds with early protein intake and early oral iron supplementation (6 mg/kg from days 7 to 10 of life, if milk feeds 60 mL/kg/d) combined with a restrictive transfusion policy in infants < 32 weeks' gestation and < 1500 g birth weight. Data on blood transfusions in VLBW infants during the first 6 weeks of life collected before the start of the new regimen (period I) were compared with data in consecutively born VLBW infants after the introduction of the management guideline (period II). Age (in days) when milk feeds and oral iron supplements were introduced was recorded. Statistical analysis used Wilcoxon signed-rank test. VLBW infants in period I ( N = 18, median birth weight 1001 g [727; 1158]) received a median of four transfusions (0.75; 9) compared with 1.5 (0.75; 5, P = 0.01) VLBW infant transfusions in period II ( N = 22, median birth weight 967 g [792; 1131]). Milk feeds of 60 mL/kg/d were achieved on median day 12 (6; to 16), and iron was introduced on median day 38 (21; to 44) in period I compared with milk feeds on day 9 (7; 15, P = 0.05) and oral iron on day 16 (11; 21, P < 0001) in period II. The combination of a 30-second delay in cord clamping, early protein and iron, and a change of transfusion thresholds reduced the number of blood transfusions by half.