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.

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.

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.

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.

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.

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).

Interrupter resistance to measure dose-response to salbutamol in wheezy preschool children.

AIM: Using a non-invasive lung function technique (interrupter resistance, Rint), we aimed to determine whether a dose-response to salbutamol could be detected in wheezy preschool children and if so, which dose of salbutamol should be administered to routinely evaluate bronchial reversibility. METHOD: Wheezy children (3 to <7 years) were enrolled in a prospective multicenter study. Rint was measured at baseline, and after random assignment to a first dose (100 or 200 µg) and a second dose (cumulative dose: 400, 600, or 800 µg) of salbutamol. Data were analyzed using mixed modeling approach with an inhibitory maximal effect (Imax ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses. RESULTS: Final results were available in 99 children out of 106 children included. The model adequately fitted the data, showing satisfactory goodness-of-fit plots and a low residual error of 8%. Children with uncontrolled symptoms had lower Imax (ie, showed less reversibility) compared to children with totally/partly controlled symptoms (0.23 vs. 0.31, P < 0.001). Dose to reach 50% of Imax (D50 ) was 51 µg. According to simulations, 88.1% of children with significant reversibility at dose 800 µg would already show significant reversibility at 400 µg. CONCLUSION: Interrupter resistance was able to measure a dose-response curve to salbutamol in wheezy preschool children, which was similar to that of older patients. Young children require a high dose of salbutamol to correctly assess airway bronchodilator response, especially these with poor symptom control.

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.

Infant home respiratory monitoring using pulse oximetry.

Respiratory rate (RR) is a valuable early marker of illness in vulnerable infants, but current monitoring methods are unsuitable for sustained home use. We have demonstrated accurate measurement of RR from brief recordings of pulse oximeter plethysmogram (pleth) trace in full-term neonates in hospital. This study assessed the feasibility of this method in preterm infants during overnight recordings in the home. We collected simultaneous overnight SpO2, pleth and respiratory inductive plethysmography (RIP) on 24 preterm infants in the home. RR from pleth analysis was compared with RR from RIP bands; pleth quality was assessed by the presence of visible artefact. Median (range) RR from RIP and pleth were not significantly different at 42 (25-65) and 42 (25-64) breaths/min. Median (range) % of epochs rejected due to artefact was 20 (8-75) for pleth and 10 (3-53) for RIP. Our results suggest that home RR monitoring by pulse oximeter pleth signal is accurate and feasible.

Acceptability of orodispersible films for delivery of medicines to infants and preschool children.

Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation of their acceptability in this age group is lacking. This study is the first to explore the initial perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers through observed administration of the type of dosage form. Placebo ODFs were administered to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over. The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers of preschool children positively rated their child's acceptance of the ODF. The intraclass correlation coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses. ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading permits, pharmaceutical companies should consider developing pediatric medicines in this format. The methodology described here is useful in assessing the acceptability of active ODF preparations and other dosage forms to children.

How can we optimise inhaled beta2 agonist dose as 'reliever' medicine for wheezy pre-school children? Study protocol for a randomised controlled trial.

BACKGROUND: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 µg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol. METHODS: This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation. DISCUSSION: The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor. TRIAL REGISTRATION: EudraCT2014-001978-33, ISRCTN15513131. Registered on 8 April 2015.

An Official American Thoracic Society/European Respiratory Society Workshop Report: Evaluation of Respiratory Mechanics and Function in the Pediatric and Neonatal Intensive Care Units.

Ready access to physiologic measures, including respiratory mechanics, lung volumes, and ventilation/perfusion inhomogeneity, could optimize the clinical management of the critically ill pediatric or neonatal patient and minimize lung injury. There are many techniques for measuring respiratory function in infants and children but very limited information on the technical ease and applicability of these tests in the pediatric and neonatal intensive care unit (PICU, NICU) environments. This report summarizes the proceedings of a 2011 American Thoracic Society Workshop critically reviewing techniques available for ventilated and spontaneously breathing infants and children in the ICU. It outlines for each test how readily it is performed at the bedside and how it may impact patient management as well as indicating future areas of potential research collaboration. From expert panel discussions and literature reviews, we conclude that many of the techniques can aid in optimizing respiratory support in the PICU and NICU, quantifying the effect of therapeutic interventions, and guiding ventilator weaning and extubation. Most techniques now have commercially available equipment for the PICU and NICU, and many can generate continuous data points to help with ventilator weaning and other interventions. Technical and validation studies in the PICU and NICU are published for the majority of techniques; some have been used as outcome measures in clinical trials, but few have been assessed specifically for their ability to improve clinical outcomes. Although they show considerable promise, these techniques still require further study in the PICU and NICU together with increased availability of commercial equipment before wider incorporation into daily clinical practice.

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.

The association of children's distress during venepuncture with parent and staff behaviours.

Venepuncture and other needle-related procedures can distress children and have a lasting negative impact. Adults' behaviour during these procedures may affect children's reactions. However, the literature is contradictory and rarely considers verbal and non-verbal behaviour together. This study therefore examined the effect of adults' verbal and non-verbal behaviour on children's distress during venepuncture. Participants comprised 51 child and carer dyads and 10 staff members. Child anxiety was measured before the procedure. The procedure was recorded. The resulting audio-visual data were coded using the Child-Adult Medical Procedure Interaction Scale-Revised. Correlation analysis identified variables that were significantly associated with child distress: child anxiety, carer distress-promoting behaviour, staff distress-promoting behaviour and intimate distance. These were included in a path diagram of child distress. Exploration of the diagram identified that children's anxiety was mostly strongly associated with children's distress during venepuncture. Staff and carer behaviour did not increase children's distress. The results suggest interventions to reduce children's distress during venepuncture may be more effective if they focus on reducing children's anxiety beforehand.