Improvements in Clinical Outcomes in Children with Cystic Fibrosis aged Six and 16 years.

Aims Our aim was to assess if outcomes for cystic fibrosis (CF) patients at six & sixteen years of age have improved in the last 17 years looking at FEV1, BMI and death. Methods A retrospective observational study using a prospectively maintained database of CF patients at Cork University Hospital. Results 84 patients were included in the 16-year-old data and 89 patients were included in the six-year-old data. The mean FEV1 and BMI (16 years) for the 2002-2007 group was 72.9±21.0% and 18.9±2.53 respectively, 2008-2013 group was 75.4±27.2% and 19.8±2.7 and for the 2014-2018 group was 95.2±16.0% and 22.9±4.1. The percentage of patients (16 years) with chronic pseudomonas status was 37.9% (11/30) in the 2002-2007 group, 51.6 % (16/31) in the 2008-2013 group and 4.2% (1/24) in the 2014-2018 group. The relationship between FEV1 and FVC with BMI remained significant in multivariate analysis (P <0.001). The mean FEV1 (six years) for the 2002-2007 group was 90.7±16.1%, 2008-2013 group was 99.3±17.9% and for the 2014-2018 group was 100.9±15.8%. Conclusions Improvements in FEV1 and BMI aged six and 16 years are notable as well as a significant decline in the number of patients with chronic pseudomonas.

Molecular epidemiology of Mycobacterium abscessus complex isolates in Ireland.

BACKGROUND: The Mycobacterium abscessus complex are the rapidly growing mycobacteria (RGM) most commonly causing lung disease, especially in cystic fibrosis (CF) patients. Ireland has the world's highest CF incidence. The molecular epidemiology of M. abscessus complex in Ireland is unreported. METHODS: We performed rpoB gene sequencing and multi-locus sequence typing (MLST) on M. abscessus complex strains isolated from thirty-six patients in 2006-2012 (eighteen known CF patients). RESULTS: Twenty-eight strains (78%) were M. abscessus subsp. abscessus, eight M. abscessus subsp. massiliense, none were M. abscessus subsp. bolletii. Sequence type 1 (ST1) and ST26 (M. abscessus subsp. abscessus) were commonest. Seven M. abscessus subsp. abscessus STs (25%) were novel (two with novel alleles). Seven M. abscessus subsp. massiliense STs were previously reported (88%), including two ST23, the globally successful clone. In 2012, of 552 CF patients screened, eleven were infected with M. abscessus complex strains (2%). CONCLUSIONS: The most prevalent M. abscessus subsp. abscessus and M. abscessus subsp. massiliense strains in Ireland belong to widely-distributed STs, but there is evidence of high M. abscessus subsp. abscessus diversity.

Diagnosis and treatment of sleep related breathing disorders in children: 2007 to 2011.

Sleep related breathing disorders (SRBD) have historically been under-recognised and under-treated. Obstructive sleep apnoea (OSA) affects approximately 3% of children. In line with the increased recognition of SRBD there has been an increase in demand for diagnostic services. We determined the awareness of SRBD amongst Irish paediatricians, examined the provision of sleep services to children throughout the country between 2007 and 2011 and audited diagnostic sleep services in a tertiary centre in 2011. Amongst respondents there was an awareness of SRBD but a poor understanding of diagnostic evaluation with 31/46 (67) referring to inappropriate services. There has been a sharp increase in both diagnostic sleep tests (433-1793 [414]) and in the use of non-invasive ventilation (NIV) (31-186 [627]) for treatment of SRBD between 2007 and 2011. Paediatric sleep services are organized in an ad-hoc manner nationally with significant service variation. The use of domiciliary overnight oximetry reduced the requirement for more formal polysomnography by 70%.

BCG protects toddlers during a tuberculosis outbreak.

In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

Long-acting beta2-agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma.

BACKGROUND: Long-acting inhaled beta2-adrenergic agonists are recommended as 'add-on' medication to inhaled corticosteroids in the maintenance therapy of asthmatic adults and children aged two years and above. OBJECTIVES: To quantify in asthmatic patients the safety and efficacy of the addition of long-acting beta2-agonists to inhaled corticosteroids on the incidence of asthma exacerbations, pulmonary function and other measures of asthma control. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers, until April 2004. SELECTION CRITERIA: RCTs were included that compared the addition of inhaled long-acting beta2-agonists to corticosteroids with inhaled corticosteroids alone for asthma therapy in children aged two years and above and in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptom scores, adverse events and withdrawal rates. MAIN RESULTS: Of 594 identified citations, 49 trials met the inclusion criteria: 27 full-text publications, one unpublished full-text report and 21 abstracts. Twenty-three citations (21 abstracts and two full-text publications) provided data in insufficient detail, 26 trials contributed to this systematic review. All but three trials were of high methodological quality. Most interventions (N = 26) were of four-month duration or less. Eight trials focused on children and 18 on adults, with participants generally symptomatic with moderate airway obstruction despite their current inhaled steroid regimen. If a trial had more than one intervention or control group, additional control to intervention comparisons were considered separately. Formoterol (N = 17) or salmeterol (N = 14) were most frequently added to low-dose inhaled corticosteroids (200 to 400 microg/day of beclomethasone (BDP) or equivalent). The addition of a daily long-acting beta2-agonist (LABA) reduced the risk of exacerbations requiring systemic steroids by 19% (relative risk (RR) 0.81, 95% CI 0.73 to 0.90). The number needed to treat for one extra patient to be free from exacerbation for one year was 18 (95% CI 13 to 33). The addition of LABA significantly improved FEV1 (weighted mean difference (WMD) 170 mL, 95% CI 110 to 240) using a random-effects model, increased the proportion of symptom-free days (WMD 17%, 95% CI 12 to 22, N = 6 trials) and rescue-free days (WMD 19%, 95% CI 12 to 26, N = 2 trials). The group treated with LABA plus inhaled corticosteroid showed a reduction in the use of rescue short-acting beta2-agonists (WMD -0.7 puffs/day, 95% CI -1.2 to -0.2), experienced less withdrawals due to poor asthma control (RR 0.5, 95% CI 0.4 to 0.7) and less withdrawals due to any reason (RR 0.9, 95% CI 0.8 to 0.98), using a random-effects model. There was no group difference in risk of overall adverse effects (RR 0.98, 95% CI 0.92 to 1.05), withdrawals due to adverse health events (RR 1.29, 95% CI 0.96 to 1.75) or specific adverse health events. AUTHORS' CONCLUSIONS: In patients who are symptomatic on low to high doses of inhaled corticosteroids, the addition of a long-acting beta2-agonist reduces the rate of exacerbations requiring systemic steroids, improves lung function, symptoms and use of rescue short-acting beta2-agonists. The similar number of serious adverse events and withdrawal rates in both groups provides some indirect evidence of the safety of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.

Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma.

BACKGROUND: In asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled beta2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. OBJECTIVES: To determine, in asthmatic patients, the effect of the combination of long-acting beta2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the incidence of asthma exacerbations, on pulmonary function and on other measures of asthma control and to look for characteristics associated with greater benefit for either treatment option. SEARCH STRATEGY: We identified randomized controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until April 2004. SELECTION CRITERIA: RCTs were included that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children aged 2 years and older, and in adults with asthma. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of rescue beta2 agonists, adverse events and withdrawal rates. The meta-analysis was done with RevMan Analyses and the meta-regression, with Stata. MAIN RESULTS: Of 593 citations identified, 30 (three pediatric; 27 adult) trials were analysed recruiting 9509 participants, including one study providing two control-intervention comparisons. Only one trial included corticosteroid-naive patients. Participants were symptomatic, generally (N=20 trials) presenting with moderate (FEV1 60-79% of predicted) rather than mild airway obstruction. Trials tested the combination of salmeterol (N=22) or formoterol (N=8) with a median of 400 mcg of beclomethasone or equivalent (BDP-eq) compared to a median of 800 to 1000 mcg/day of BDP-eq. Trial duration was 24 weeks or less in all but four trials. There was no significant group difference in the rate of patients with exacerbations requiring systemic corticosteroids [N=15, RR=0.88 (95% CI: 0.77, 1.02)]. The combination of LABA and ICS resulted in greater improvement from baseline in FEV1 [N=7, WMD=0.10 L (95% CI: 0.07, 0.12)], in symptom-free days [N=8 , WMD=11.90% (95% CI:7.37, 16.44), random effects model], and in the daytime use of rescue beta2 agonists than a higher dose of ICS [N=4, WMD= -0.99 puffs/day (95% CI: -1.41, -0.58), random effects model]. There was no significant group difference in the rate of overall adverse events [N=15, RR=0.93 (95% CI: 0.84, 1.03), random effects model], or specific side effects, with the exception of a three-fold increase rate of tremor in the LABA group [N= 10, RR=2.96 (95%CI: 1.60, 5.45)]. The rate of withdrawals due to poor asthma control favoured the combination of LABA and ICS [N=20, RR=0.69 (95%CI: 0.52, 0.93)]. AUTHORS' CONCLUSIONS: In adult asthmatics, there was no significant difference between the combination of LABA and ICS and a higher dose of ICS for the prevention of exacerbations requiring systemic corticosteroids. Overall, the combination therapy led to greater improvement in lung function, symptoms and use of rescue beta2 agonists, (although most of the results are from trials of up to 24 weeks duration). There were less withdrawals due to poor asthma control in this group than when using a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor, the two options appear safe although adverse effects associated with long-term ICS treatment were seldom monitored.

Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults.

BACKGROUND: Consensus statements recommend the addition of long-acting inhaled beta2-agonists only in asthmatic patients who are inadequately controlled on inhaled corticosteroids. OBJECTIVES: To compare the efficacy of initiating anti-inflammatory therapy using the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS+LABA) as compared to inhaled corticosteroids alone (ICS alone) in steroid-naive children and adults with persistent asthma. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) through electronic database searches (Cochrane Airways Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL) until April 2004, bibliographies of identified RCTs and correspondence with manufacturers. SELECTION CRITERIA: RCTs comparing the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS + LABA) to inhaled corticosteroids (ICS) alone in steroid-naive children and adults with asthma. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by each reviewer for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of other measures of asthma control, adverse events, and withdrawal rates. MAIN RESULTS: Eighteen trials met the inclusion criteria; nine (totaling 1061 adults) contributed sufficient data to be analysed. Baseline forced expiratory volume in one minute (FEV1) was less than 80% predicted value in four trials and equal to or greater than 80% in five trials. The long-acting beta2-agonists (LABA) formoterol (N=2) or salmeterol (N=7) were added to a dose of at least 800 microg/day of beclomethasone dipropionate (BDP) equivalent of inhaled corticosteroids (ICS) in three trials and to at least 400 microg/day in the six remaining trials. Treatment with ICS plus LABA was not associated with a lower risk of exacerbations requiring oral corticosteroids than ICS alone (relative risk (RR) 1.2; 95% confidence interval (CI) 0.8 to 1.9). FEV1 improved significantly with LABA (weighted mean difference (WMD) 210 ml; 95% CI 120 to 300), as did symptom-free days (WMD 10.74%; 95% CI 1.86 to 19.62), but the change in use of rescue fast-acting beta2-agonists was not significantly different between the groups (WMD -0.4 puff/day, 95% CI -0.9 to 0.1). There was no significant group difference in adverse events (RR 1.1; 95% CI 0.8 to 1.5), withdrawals (RR 0.9; 95% CI 0.6 to 1.2), or withdrawals due to poor asthma control (RR 1.3; 95% CI 0.5 to 3.4). AUTHORS' CONCLUSIONS: In steroid-naive patients with mild to moderate airway obstruction, the initiation of inhaled corticosteroids in combination with long-acting beta2-agonists does not significantly reduce the rate of exacerbations over that achieved with inhaled corticosteroids alone; it does improve lung function and symptom-free days but does not reduce rescue beta2-agonist use as compared to inhaled steroids alone. Both options appear safe. There is insufficient evidence at present to recommend use of combination therapy rather than ICS alone as a first-line treatment.

Rectal hydrocortisone during vomiting in children with adrenal insufficiency.

AIM: To evaluate rectal hydrocortisone as an emergency glucocorticoid replacement therapy in adrenal insufficient children. METHODS: A parental questionnaire evaluated preferred treatment, problems or benefits of i.m. and rectal hydrocortisone, frequency and indications for administration and who administered treatment. Admissions of children with adrenal insufficiency were monitored. RESULTS: There were 39/52 families who responded to the questionnaire. 93% (26/28) preferred rectal hydrocortisone. Parents or children who previously received emergency treatment from a doctor now self-administered rectal hydrocortisone. The cost of suppositories and i.m. hydrocortisone is similar; however, storage of suppositories was inconvenient. One girl presented with pneumonia and collapse despite rectal hydrocortisone and a hydrocortisone level at admission of >2000 nmol/l with normal electrolytes. CONCLUSIONS: Rectal hydrocortisone is an acceptable and safe emergency therapy. We still advise i.m. hydrocortisone if rectal administration is not possible or with suppository extrusion.