High-flow nasal cannula therapy for infants with bronchiolitis.

BACKGROUND: Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is the most common cause of hospitalisation of infants. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality. Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen, and respiratory support. Traditionally, oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, at 2 to 3 L/kg per minute up to 60 L/min in children. It can provide some level of continuous positive airway pressure (CPAP) to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support, thus potentially lowering costs, with clinical advantages and fewer adverse effects. OBJECTIVES: To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, and Web of Science (from June 2013 to December 2022). In addition, we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles, and searched for conference abstracts. Date restrictions were imposed such that we only searched for studies published after the original version of this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/minute) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, risk of bias elements, and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy, and adverse events. MAIN RESULTS: In this update we included 15 new RCTs (2794 participants), bringing the total number of RCTs to 16 (2813 participants). Of the 16 studies, 11 compared high-flow to low-flow, and five compared high-flow to CPAP. These studies included infants less than 24 months of age as stated in our selection criteria. There were no significant differences in sex. We found that when comparing high-flow to low-flow oxygen therapy for infants with bronchiolitis there may be a reduction in the total length of hospital stay (mean difference (MD) -0.65 days, 95% confidence interval (CI) -1.23 to -0.06; P < 0.00001, I2 = 89%; 7 studies, 1951 participants; low-certainty evidence). There may also be a reduction in the duration of oxygen therapy (MD -0.59 days, 95% CI -1 to -0.18; P < 0.00001, I2 = 86%; 7 studies, 2132 participants; low-certainty evidence). We also found that there was probably an improvement in respiratory rate at one and 24 hours, and heart rate at one, four to six, and 24 hours in those receiving high-flow oxygen therapy when compared to pre-intervention baselines. There was also probably a reduced risk of treatment escalation in those receiving high-flow when compared to low-flow oxygen therapy (risk ratio (RR) 0.55, 95% CI 0.39 to 0.79; P = 0.001, I2 = 43%; 8 studies, 2215 participants; moderate-certainty evidence). We found no difference in the incidence of adverse events (RR 1.2, 95% CI 0.38 to 3.74; P = 0.76, I2 = 26%; 4 studies, 1789 participants; low-certainty evidence) between the two groups. The lack of comparable outcomes in studies comparing high-flow and CPAP, as well as the small numbers of participants, limited our ability to perform meta-analysis on this group. AUTHORS' CONCLUSIONS: High-flow nasal cannula therapy may have some benefits over low-flow oxygen for infants with bronchiolitis in terms of a greater improvement in respiratory and heart rates, as well as a modest reduction in the length of hospital stay and duration of oxygen therapy, with a reduced incidence of treatment escalation. There does not appear to be a difference in the number of adverse events. Further studies comparing high-flow nasal cannula therapy and CPAP are required to demonstrate the efficacy of one modality over the other. A standardised clinical definition of bronchiolitis, as well as the use of a validated clinical severity score, would allow for greater and more accurate comparison between studies.

Widespread alterations in the peripheral blood innate immune cell profile in cystic fibrosis reflect lung pathology.

Cystic fibrosis (CF) is caused by mutations to the CF transmembrane conductance regulator (CFTR) gene. CFTR is known to be expressed on multiple immune cell subtypes, dendritic cells, monocytes/macrophages, neutrophils and lymphocytes. We hypothesized that the lack of CFTR expression on peripheral blood innate immune cells would result in an altered cell profile in the periphery and that this profile would reflect lung pathology. We performed a flow cytometric phenotypic investigation of innate immune cell proportions in peripheral blood collected from 17 CF patients and 15 age-matched healthy controls. We observed significant differences between CF patients and controls in the relative proportions of natural killer (NK) cells, monocytes and their subsets, with significant correlations observed between proportions of NK and monocyte cell subsets and lung function (forced expiratory volume in 1 sec, % predicted; FEV1% predicted) in CF patients. This study demonstrates the widespread nature of immune dysregulation in CF and provides a basis for identification of potential therapeutic targets. Modulation of the distinct CF-related immune cell phenotype identified could also be an important biomarker for evaluating CFTR-targeted drug efficacy.

Parental knowledge, beliefs and management of childhood fever in Australia: A nationwide survey.

WHAT IS KNOWN AND OBJECTIVE: Fever, one of the most common symptoms of illness experienced by children, often creates undue parental anxiety about the consequences of fever, which can lead to overtreatment. The full extent of this problem in Australia is not known. This study aimed to describe parents' knowledge, beliefs and perceptions about childhood fever and its management, and identify any predictors of the burden on parents when children are febrile. METHODS: This was a cross-sectional web-based survey of parents living in Australia. Parents with at least 1 child <6 years were recruited via Facebook. Demographic information, parental fever knowledge and beliefs and responses to the Parent Fever Management Scale, a measure of parental burden, were collected and analysed. RESULTS AND DISCUSSION: Of the 12 179 parents who completed the survey, 42.0% knew that a temperature above 38°C constitutes a fever, with 33.4% underestimating the temperature of a fever. Parents believed that there were many harms associated with untreated fever, namely seizures (71.8%), dehydration (63.6%), serious illness (43.0%) and brain damage (36.8%). Phobic beliefs were more common among parents who underestimated the temperature of a fever. Identification of health professionals as a main information source about fever did not significantly improve knowledge or reduce fears. Up to 65.0% of respondents indicated that they practice non-evidence-based strategies to reduce temperature. The belief that 'every child with a fever should be treated with medication to lower temperature' was the strongest predictor of parental burden (ß = 0.245, P < 0.001). WHAT IS NEW AND CONCLUSION: Poor parental knowledge and misconceptions surrounding fever and its management are still common among parents throughout Australia. Large-scale, sustainable educational interventions are needed to dispel misconceptions and concerns about fever, encourage appropriate and safe care of febrile children.

Emergency department presentations of febrile children to an Australian public hospital.

AIM: We investigated the presentations of children with unspecified fever to an Australian emergency department (ED): (i) to determine the proportion of these presentations that could be classified as potentially avoidable and (ii) to identify factors associated with an increased risk of hospital admission. METHODS: This study retrospectively identified and described children aged <6 years who presented to the Royal Hobart Hospital (Tasmania, Australia) ED with unspecified fever (ICD-10-AM code R50.9) between January 2013 and December 2015, using data from the ED information system and digital medical records. The Australian Institute of Health and Welfare method was used to estimate the number of potentially avoidable general practitioner-type presentations. Predictors of hospital admission were determined using multivariate logistic regression. RESULTS: A total of 459 patients aged <6 years presented to the ED with a primary diagnosis description of unspecified fever. Of these, 30.7% were classed as potentially avoidable general practitioner-type presentations. Overall, 26.1% of presentations resulted in admission to hospital. Administration of intravenous fluids in the ED and a longer treat time were identified as significant predictors of a child with non-specific fever being admitted to hospital. Older age, administration of antipyretics in the ED and presentations triaged as semi-urgent and non-urgent significantly reduced the probability of admission. CONCLUSIONS: To our knowledge, this is the first Australian study that has assessed the impact of unspecified childhood fever on an Australian ED. Further investigation of presentations classified as potentially avoidable is warranted to investigate whether these could be managed in the primary care setting.

Do children with cystic fibrosis receiving outreach care have poorer clinical outcomes than those treated at a specialist cystic fibrosis centre?

INTRODUCTION: Although cystic fibrosis (CF) centre care is generally considered ideal, children living in regional Australia receive outreach care supported by the academic CF centres. METHODS: This is a retrospective database review of children with CF treated at the Royal Children's Hospital in Melbourne and its outreach clinics in Albury (Victoria), and Tasmania. The aim was to compare the outcomes of children with CF managed at an academic centre with that of outreach care, using lung function, nutritional status and Pseudomonas aeruginosa colonisation. Three models of care, namely CF centre care, Shared care and predominantly Local care, were compared, based on the level of involvement of CF centre multidisciplinary team. In our analyses, we controlled for potential confounders, such as socio-economic status and the degree of remoteness, to determine its effect on the outcome measures. RESULTS: There was no difference in lung function, i.e. forced expiratory volume in 1 s (FEV1 ), the prevalence of Pseudomonas aeruginosa colonisation or nutritional status (body mass index (BMI)) between those receiving CF centre care and various modes of outreach care. Neither socio-economic status, measured by the Socio-Economic Index for Area (SEIFA) for disadvantage, nor distance from an urban centre (Australian Standard for Geographical Classification (ASGC)) were associated with lung function and nutritional outcome measures. There was however an association between increased Pseudomonas aeruginosa colonisation and poorer socio-economic status. CONCLUSION: Outcomes in children with CF in regional and remote areas receiving outreach care supported by an academic CF centre were no different from children receiving CF centre care.

Off-label use of medicines in paediatric inpatients at an Australian teaching hospital.

AIM: The study aims to investigate the prevalence of off-label prescribing in the general paediatric ward at a major teaching hospital in Tasmania, Australia. METHOD: The drug charts and medical records from two groups of 150 consecutive paediatric patients, admitted 6 months apart in July 2009 and January 2010, were studied retrospectively. Patients were required to spend at least one night in hospital and be aged less than 12 years. Each prescribed drug was compared with the approved product information to determine if the usage was off-label. Data concerning documented informed consent and adverse drug reactions were also recorded. RESULTS: Three hundred patients were prescribed a total of 887 medicines. Of these, 31.8% were off-label and 57.3% of children received an off-label medication. There was no significant seasonal variation in patient characteristics or prescriptions. Drugs were most commonly off-label due to their dosage or frequency of administration. Of the 106 different drugs used, the use of 51 was off-label on at least one occasion, and for 30 drugs their use was off-label on more than 75% of occasions. The drugs most commonly used off-label were oxycodone, salbutamol and paracetamol. No informed consent documentation was identified, and two of five recorded adverse drug reactions were associated with off-label drug use. CONCLUSION: Off-label use of medicines occurred frequently in paediatric inpatients. The available evidence often supported off-label medication use. An improved system for the revision of approved drug information and an Australian guideline for paediatric prescribing are needed.

Review of the management of childhood asthma in Tasmania.

AIM: To review the supply of medications to children with asthma and parent-reported management of childhood asthma in Tasmania and highlight evidence-practice gaps for future interventions. METHODS: Participating pharmacies ran a software application that extracted data from dispensing records and helped to identify children with asthma. Parents of identified children were mailed a survey evaluating components of asthma management. Dispensing and survey data were analysed. RESULTS: A total of 939 children from 23 pharmacies were identified by the software and deemed eligible for inclusion. Surveys were received from 353 (37.6%) parents. In the past year, short-acting beta-2 agonists were supplied to 56.1% of the cohort, preventers to 76.5% (inhaled corticosteroids 52.3%; leukotriene receptor antagonists 31.3%; inhaled cromones 0.6%), long-acting beta-2 agonists (LABAs) to 25.7% and oral corticosteroids to 21.5%. Approximately half of the children receiving inhaled corticosteroids were concurrently receiving a LABA. Among children with indicators of inadequately controlled asthma, up to 73.7% of their parents reported that their asthma was adequately controlled, up to 38.2% did not possess an Asthma Action Plan, up to 36.8% were not regularly using a spacer and up to 22.8% had not received a preventer. CONCLUSION: These results indicate gaps in childhood asthma management, in particular, undersupply of preventers in high-risk patient groups, high supply of LABAs and insufficient spacer and asthma action plan usage. These areas should be targeted for interventions to improve childhood asthma management.

Supporting cystic fibrosis with ICT.

ICT use in cystic fibrosis management provides an alternative means of information supply to individuals, families, health care professionals and other stakeholders. The purpose of this paper is to present the evolution of a series of projects culminating in a project that translates the previous research into practice. In this paper the sequential nature of the projects will be detailed. The three projects explored are the Pathways Home for Respiratory Illness Project (Pathways Home), Enhancing Self-Efficacy for Self-Management in People with Cystic Fibrosis and the Tasmanian Community Fund Project (myCF pilot).

Pandoraea pnomenusa Isolated from an Australian Patient with Cystic Fibrosis.

Pandoraea species are considered as emerging pathogens in people with cystic fibrosis (CF). The contribution of these organisms to disease progression in CF patients is not fully understood owing in large measure to the scant reports in clinical and research literature describing their colonization of CF patients and their associated virulence determinants. In an effort to increase awareness and evidence for Pandoraea spp. infection in people with CF, and to stimulate research aimed at unraveling the pathogenic properties of Pandoraea, we report a case of a 26-year-old Australian (Tasmanian) man with CF who was chronically infected with Pandoraea pnomenusa for at least one year prior to his death from respiratory failure. In addition, we describe for the first time evidence suggesting that this bacterium is a facultative anaerobe and report on the availability of a whole genome sequence for this organism. To the best of our knowledge, this report represents only the second clinical case study of P. pnomenusa infection in the world, and the first in an Australian CF patient.

High peripheral blood th17 percent associated with poor lung function in cystic fibrosis.

People with cystic fibrosis (CF) have been reported to make lung T cell responses that are biased towards T helper (Th) 2 or Th17. We hypothesized that CF-related T cell regulatory defects could be detected by analyzing CD4+ lymphocyte subsets in peripheral blood. Peripheral blood mononuclear cells from 42 CF patients (6 months-53 years old) and 78 healthy controls (2-61 years old) were analyzed for Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17+), Treg (FOXP3+), IL-10+ and TGF-ß+ CD4+ cells. We observed higher proportions of Treg, IL-10+ and TGF-ß+ CD4+ cells in CF adults (≥ 18 years old), but not children/adolescents, compared with controls. Within the CF group, high TGF-ß+% was associated with chronic Pseudomonas aeruginosa lung infection (p < 0.006). We observed no significant differences between control and CF groups in the proportions of Th1, Th2 or Th17 cells, and no association within the CF group of any subset with sex, CFTR genotype, or clinical exacerbation. However, high Th17% was strongly associated with poor lung function (FEV1 % predicted) (p = 0.0008), and this association was strongest when both lung function testing and blood sampling were performed within one week. Our results are consistent with reports of CF as a Th17 disease and suggest that peripheral blood Th17 levels may be a surrogate marker of lung function in CF.