The efficacy and safety of fluticasone/salmeterol compared to fluticasone in children younger than four years of age.

BACKGROUND: Fluticasone propionate 50 µg/salmeterol xinafoate 25 µg (FP/SAL) is widely used in adults and children with asthma, but there is sparse information on its use in very young children. METHODS: This was a randomized, double-blind, multicentre, controlled trial conducted in children aged 8 months to 4 years. During a 2-week run-in period, they all received FP twice daily. At randomization, they commenced FP/SAL or FP twice daily for 8 weeks. All were then given FP/SAL only, in a 16-week open-label study continuation. Medications were inhaled through an AeroChamber Plus with attached face mask. The primary end-point was mean change in total asthma symptom scores from baseline to the last 7 days of the double-blind period. Analyses were undertaken in all children randomized to treatment and who received at least one dose of study medication. RESULTS: Three hundred children were randomized 1:1 to receive FP/SAL or FP. Mean change from baseline in total asthma symptom scores was -3.97 for FP/SAL and -3.01 with FP. The between-group difference was not statistically significant (P = 0.21; 95% confidence interval: -2.47, 0.54). No new safety signals were seen with FP/SAL. CONCLUSION: This is the first randomized, double-blind study of this size to evaluate FP/SAL in very young children with asthma. FP/SAL did not show superior efficacy to FP; no clear add-on effect of SAL was demonstrated. No clinically significant differences in safety were noted with FP/SAL usage.

Telemedicine is the way forward for the management of cystic fibrosis- the case against.

It is reasonable to suggest that Telemedicine could help in the management of chronic diseases by giving patients more flexibility to remain at home with opportunities to forward electronic data to healthcare professionals, reduce hospital emergency attendances and reduce overall costs. The reality, particularly in cystic fibrosis care, is this has not happened. There is concern that home-generated lung function data is of poor quality and virtually no studies show improved outcomes. The UK has a poor record in developing novel IT programmes and we need many more well designed clinical studies in Telemedicine before wading in with ill-conceived expensive plans just because the idea seems interesting.

A review of prednisolone prescribing for children with acute asthma in the UK.

INTRODUCTION: Worldwide asthma guidelines recommend short courses of oral prednisolone in children with acute exacerbations generating high prescription numbers. There is a paucity of evidence to inform the optimal dose and course duration. This has led to a variation in the recommendations for prednisolone prescribing. Our objective was to assess prednisolone prescribing practise for children with acute asthma in a representative sample of UK prescribers. METHODS: We developed an online questionnaire asking prescribers the prednisolone dosage, course duration and formulation used, whether they discussed oral prednisolone side effects with the family and at what child's age they changed from prescribing soluble to non-soluble formulations. This was sent to 1006 UK prescribers including Paediatric Respiratory Consultants, doctors in training, asthma nurses and General Practitioners. RESULTS: 200 complete responses were received (response rate 20%). The majority of surveyed prescribers follow the British National Formulary for Children recommendations on dosage rather than those included in the British Thoracic Society and the Scottish Intercollegiate Guidelines Network. Despite this, we highlighted a 4-fold variation in prednisolone dosages for acute asthma. The majority of prescribers chose 3 days as the course duration. High use of soluble formulations was highlighted. CONCLUSIONS: There is wide variation in the dose of prednisolone prescribed for children with acute asthma in the UK. This reflects a relative lack of evidence that needs addressing.

The development of a national children's formulary.

The British National Formulary has been in existence for over 30 years. The prescribing of medicines for children has been less well organized. Many medicines used in children have never been tested in the appropriate age groups and have been prescribed 'off-label'. This has led to safety issues and concerns that children continued to be treated as second-class citizens. The first attempt at the development of a national formulary specifically for prescribing in children occurred in 1999 with the publication of 'Medicines for Children'. This generated much national and international interest resulting in the government agreeing to fund the development and production of the first British National Formulary for Children in 2005. This article charts the process and progress of the formulary to the present day.

Is hydrogen cyanide a marker of Burkholderia cepacia complex?

Biofilm cultures of Burkholderia cepacia complex (BCC) infection have been found to generate the nonvolatile cyanide ion. We investigated if gaseous hydrogen cyanide (HCN) was a marker of BCC infection. Selected ion flow tube mass spectrometry analysis showed HCN was not elevated in the headspace of planktonic or biofilm cultures or in the exhaled breath of adult cystic fibrosis patients with chronic BCC infection. HCN is therefore not an in vitro or in vivo marker of BCC.

Implementation of a primary care asthma management quality improvement programme across 68 general practice sites.

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p < 0.001) after the intervention. The odds ratio of reporting good asthma control following the intervention was 1.15 (95% CI 1.09-1.22), p < 0.0001. This asthma management programme produced modest but highly statistically significant improvements in asthma outcomes. Key lessons learnt from this small-scale implementation will enable the methodology to be improved to maximise benefit in a larger scale role out.

Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: effects on bronchial hyperresponsiveness in children.

BACKGROUND: The CHRNA 3 and 5 genes on chromosome 15 encode the alpha subunits of the nicotinic acetylcholine receptor, mediating airway cholinergic activity. Polymorphisms are associated with cigarette smoking, chronic obstructive pulmonary disease, and lung cancer. AIMS: To determine possible associations between CHRNA 3/5 SNP rs8034191 and asthma or lung function in children in one local and one replicate multinational population, and assess if tobacco smoke modified the associations. MATERIALS AND METHODS: The rs8034191 SNP genotyped in 551 children from the environment and childhood asthma (ECA) birth cohort study in Oslo, Norway, and in 516 families from six European centers [the Genetics of Asthma International Network (GAIN) study] was tested for genotypic or allelic associations to current or history of asthma, allergic sensitization (≥ one positive skin prick tests), bronchial hyperresponsiveness (BHR), and lung function (FEV(1%) of predicted and FEV(1) /FVC ratio over/ below the 5th percentile). RESULTS: Although the TT and CT genotypes at SNP rs 8034191 were overall significantly associated with BHR (OR = 3.9, 95% CI 1.5-10.0, p = 0.005), stratified analyses according to exposure to maternal smoking in-utero or indoor smoking at 10 yrs of age showed significant association (OR = 4.4, 95% CI 1.5-12.6, p = 0.006 and OR 5.6, 95% CI 1.7-18.5, p = 0.004, respectively) only in the non-exposed and not in exposed children. The SNP-BHR association was replicated in the non-tobacco-smoke-exposed subjects in one of the GAIN centers (BHR associated with the T allele (p = 0.034)), but not in the collated GAIN populations. Asthma, allergic sensitization, and lung function were not associated with the rs8034191 alleles. CONCLUSION: An interaction between tobacco smoke exposure and a CHRNA3/5 polymorphism was found for BHR in children, but CHRNA3/5 was not associated with asthma or lung function.

How do children and their caregivers perceive the benefits of inhaled asthma therapy?

OBJECTIVE: Although well reported in adults, there is relatively little data on how children with asthma and their parents describe their attitudes to the disease, expectations of therapy, and perception of treatment benefit. We investigated this to determine if they differed from reports by adults with asthma. METHODS: We recruited families with an asthmatic child (4-11 years) who had recently been prescribed a change in treatment [starting inhaled corticosteroid monotherapy (ICS) or changing from ICS to inhaled corticosteroid/long-acting ß(2)-agonist combination therapy (ICS/LABA)]. Semi-structured interviews were conducted with the parents and the children if aged 7-11 years. RESULTS: We interviewed 28 parents and 13 children. All children on ICS/LABA had been changed from ICS monotherapy because of poor asthma control. Pediatric asthma had a significant impact on the whole family and both parents and children hoped the new medication would improve symptoms, increase their participation in physical activities, and decrease unscheduled visits to the GP (General Practitioner)/hospital. Positive effects of treatment change were reported by both parents and children, particularly in those changing from ICS to ICS/LABA. The most commonly reported benefits were reduced cough and wheeze, increased participation in sport or play activities, and reduced rescue medication use. These effects resulted in fewer visits to the GP/hospital and better attendance at school. CONCLUSIONS: While asthma symptoms prevent adults and children from participating in different types of activities (e.g., school, employment), children and their parents report the same benefits as previously reported in adults with asthma.

Primary Care Management of Asthma Exacerbations or Attacks: Impact of the COVID-19 Pandemic.

The COVID-19 pandemic has brought a renewed focus on appropriate management of chronic respiratory conditions with a heightened awareness of respiratory symptoms and the requirement for differential diagnosis between an asthma attack and COVID-19 infection. Despite early concerns in the pandemic, most studies suggest that well-managed asthma is not a risk factor for more severe COVID-related outcomes, and that asthma may even have a protective effect. Advice on the treatment of asthma and asthma attacks has remained unchanged. This article describes some challenges faced in primary care asthma management in adults and in teenagers, particularly their relevance during a pandemic, and provides practical advice on asthma attack recognition, classification, treatment and continuity of care. Acute attacks, characterised by increased symptoms and reduced lung function, are often referred to as exacerbations of asthma by doctors and nurses but are usually described by patients as asthma attacks. They carry a significant and underestimated morbidity and mortality burden. Many patients experiencing an asthma attack are assessed in primary care for treatment and continuing management. This may require remote assessment by telephone and home monitoring devices, where available, during a pandemic. Differentiation between an asthma attack and a COVID-19 infection requires a structured clinical assessment, taking account of previous medical and family history. Early separation into mild, moderate, severe or life-threatening attacks is helpful for continuing good management. Most attacks can be managed in primary care but when severe or unresponsive to initial treatment, the patient should be appropriately managed until transfer to an acute care facility can be arranged. Good quality care is important to prevent further attacks and must include a follow-up appointment in primary care, proactive regular dosing with daily controller therapy and an understanding of a patient's beliefs and perceptions about asthma to maximise future self-management.

Respiratory morbidity, healthcare utilisation and cost of care at school age related to home oxygen status.

UNLABELLED: The aim of the study was to determine whether respiratory morbidity, lung function, healthcare utilisation and cost of care at school age in prematurely born children who had bronchopulmonary dysplasia (BPD) were influenced by use of supplementary oxygen at home after neonatal intensive care unit discharge. Healthcare utilisation and cost of care in years 5 to 7 and respiratory morbidity (parent-completed respiratory questionnaire) and lung function measurements at least at age 8 years were assessed in 160 children. Their median gestational age was 27 (range 22-31) weeks and 65 of them had received supplementary oxygen when discharged home (home oxygen group). The home oxygen group had more outpatient attendances (p = 0.0168) and respiratory-related outpatient attendances (p = 0.0032) with greater related cost of care (p = 0.0186 and p = 0.0030, respectively), their cost of care for prescriptions (p = 0.0409) and total respiratory related cost of care (p = 0.0354) were significantly greater. There were, however, no significant differences in cough, wheeze or lung function results between the two groups. CONCLUSION: Prematurely born children who had BPD and supplementary oxygen at home after discharge had increased healthcare utilisation at school age. Whether such children require greater follow, in the absence of excess respiratory morbidity, merits investigation.

The evaluation of the correct use and ease-of use of the ELLIPTA DPI in children with asthma.

RATIONALE: Asthma studies show many children use inhalers incorrectly even after instruction. For two age groups of children with asthma, we determined the proportions who used the once-daily ELLIPTA dry-powder inhaler (DPI) correctly, and who found it easy to use. METHODS: This was a multicenter, single-arm, stratified, open-label, placebo study (NCT03478657). Children aged 5-7 and 8-11 years were trained in, and required to demonstrate, correct placebo ELLIPTA DPI use at their first clinic visit. The inhaler was used at home once daily for 28 ± 2 days. On returning to the clinic, children were randomized to an age-appropriate, ease-of-use questionnaire that had been developed and validated previously, and which rated the inhaler as "easy" or "hard" to use. Following questionnaire completion, children were then asked to demonstrate correct inhaler use. Correct use and ease-of use were assessed in each age group (co-primary endpoints) and overall (secondary endpoints). RESULTS: Of 222 enrolled children, 221 completed the study. Among children aged 5-7 years, 92% (n = 81/88) demonstrated correct ELLIPTA use on their first attempt, compared with 93% (n = 124/133) aged 8-11 years. Of these children, 98% (5-7 years: n = 79/81; 8-11 years: n = 121/124) rated the inhaler easy to use. Overall, 93% (n = 205/221) demonstrated correct inhaler use on their first attempt, and 98% (n = 200/205) rated it easy to use. CONCLUSION: ELLIPTA DPI was used correctly and easily by most children on their first attempt without additional training.