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The introduction of NBS in Ireland in July 2011, provided a unique opportunity to investigate clinical outcomes using a comparative historical cohort study. Clinical cohort: children clinically diagnosed with CF born 1 July 2008 to 30 June 2011, and NBS cohort: children diagnosed with CF through NBS born 1 July 2011 to 30 June 2016. Clinical data were collected from the CF Registry of Ireland, medical charts, and data on weight/height before diagnosis from public health nurses and family doctors. SPSS was used for analysis. A total of 232 patients were recruited (response 93%) (93 clinically diagnosed, 139 NBS-detected). Following exclusions of meconium ileus (MI) (40), diagnosis outside Ireland (4), and being designated as CFSPID (2), a total of 77 clinically diagnosed patients and 109 NBS detected children were included in analysis. Over half were homozygous for F508del mutation. Being clinically diagnosed was independently associated with hospitalization for infective exacerbation of CF

Parents of children with cystic fibrosis (CF) are at risk of depression and anxiety symptoms, yet, they are an under-researched group. This national cross-sectional study investigated the prevalence of anxiety and depression in parents of children with CF, and examined the associations between these symptoms and their child’s physical health and quality of life. A total of 203 parents of children attending nine paediatric CF clinics across Ireland filled out a questionnaire pack containing: a background information questionnaire; the Hospital Anxiety and Depression Scale (HADS); the Centre for Epidemiological Studies Depression Scale (CES-D); and, the Cystic Fibrosis Quality of Life Scale—Revised Edition (CFQ-R). According to the HADS, 38% of parents had elevated anxiety and 12% had elevated depression symptoms. Just over a fifth (20.7%) had elevated depression symptoms on the CES-D. Mothers had significantly higher levels of anxiety than fathers. There were statistically significant negative linear correlations between parents’ HADS anxiety and depression scores and their child’s pulmonary function, and between parents’ HADS anxiety and depression scores and their child’s quality of life. These results indicate that parents are at risk of depression and anxiety symptoms, and that these are associated with the physical health and quality of life of their child with CF. The findings support the need for parents to have mental health screening annually in CF services, as recommended in international guidelines. There is also a need to integrate a family-centred approach into CF services with appropriate supports and mental health referral pathways for parents.

Patient registries have the potential to collect and analyze high-quality postauthorization data on new medicines.We used cystic fibrosis (CF) registry data to assess outcomes after the initiation of ivacaftor, a CF transmembrane conductance regulator (CFTR) potentiator approved for the treatment of CF with a defective gating CFTR mutation.Longitudinal trends were examined using mixed-effects regression analysis in 80 ivacaftor-treated patients with CF aged 6 to 56 years registered with the CF Registry of Ireland with at least 36 months of before and after commencement data. The effects of ivacaftor treatment on forced expiratory volume in 1 second (FEVIn the 36 months after ivacaftor initiation, FEVIn this study of real-world CF registry data, clinical outcomes improved and healthcare resource utilization decreased after commencing ivacaftor.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable respiratory disease. COPD exacerbations are associated with worse quality of life, increased hospitalisations, and increased mortality. Currently available pharmacological interventions have variable impact on exacerbation frequency. The anti‐inflammatory effects of statins may lead to decreased pulmonary and systemic inflammation, resulting in fewer exacerbations of COPD. Several observational studies have shown potential benefits of statins for patients with COPD. OBJECTIVES: This review aims to evaluate available evidence on benefits and harms associated with statin therapy compared with placebo as adjunct therapy for patients with COPD. Primary objectives include the following. • To determine whether statins reduce mortality rates in COPD. • To determine whether statins reduce exacerbation frequency, improve quality of life, or improve lung function in COPD. • To determine whether statins are associated with adverse effects. SEARCH METHODS: We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search on 20 May 2019. SELECTION CRITERIA: Parallel, randomised controlled trials recruiting adults with COPD. DATA COLLECTION AND ANALYSIS: We used standard methods as expected by Cochrane. Prespecified primary outcomes were number of exacerbations, all‐cause mortality, and COPD‐specific mortality. MAIN RESULTS: Eight studies including 1323 participants with COPD were included in the review. Participants had a mean age of 61.4 to 72 years, and most were male (median 73.4%). Mean baseline forced expiratory volume in one second (FEV₁) ranged from 41% to 90% predicted. All studies compared moderate‐ or high‐intensity statin therapy versus placebo. The duration of treatment ranged from 12 weeks to 36 months. We found no statistically significant difference between statins and placebo in our primary outcome of number of exacerbations per person‐year (mean difference (MD) ‐0.03, 95% confidence interval (CI) ‐0.25 to 0.19, 1 trial, 877 participants), including number of exacerbations requiring hospitalisation per person‐year (MD 0.00, 95% CI ‐0.10 to 0.10, 1 trial, 877 exacerbations). This evidence was of moderate quality after downgrading for unclear risk of bias. Our primary outcomes of all‐cause mortality (odds ratio (OR) 1.03, 95% CI 0.61 to 1.74, 2 trials, 952 participants) and COPD‐specific mortality (OR 1.25, 95% CI 0.38 to 4.13, 1 trial, 877 participants) showed no significant difference between statins and placebo, with wide confidence intervals suggesting uncertainty about the precision of the results. This evidence was of low quality after downgrading for unclear risk of bias and imprecision. Results of the secondary outcomes analysis showed no clear differences between statins and placebo for FEV₁ (% predicted) (MD 1.18, 95% CI ‐2.6 to 4.97, 6 trials, 325 participants) but did show a statistically significant improvement in FEV₁/forced vital capacity (FVC) (MD 2.66, 95% CI 0.12 to 5.2; P = 0.04; 6 trials, 325 participants). A sensitivity analysis excluding two trials at high risk of bias showed no statistically significant difference in FEV₁/FVC (MD 2.05, 95% CI ‐0.87 to ‐4.97; P = 0.17; 4 trials, 255 participants). We also found no significant differences between the two groups in functional capacity measured by six‐minute walk distance in metres (MD 1.79, 95% CI ‐52.51 to 56.09, 3 trials, 71 participants), with wide confidence intervals suggesting uncertainty about the precision of the results. Results show no clear difference in quality of life, which was reported in three trials, and a slight reduction in C‐reactive protein (CRP) in the intervention group, which was statistically significant (MD ‐1.03, 95% CI ‐1.95 to ‐0.11; I² = 0%, P = 0.03; 3 trials, 142 participants). We noted a significant reduction in interleukin (IL)‐6 in the intervention group (MD ‐2.11, 95% CI ‐2.65 to ‐1.56; I² = 0%, P ≤ 0.00001; 2 trials, 125 participants). All trials mentioned adverse events and indicated that statins were generally well tolerated. One study reported adverse events in detail and indicated that rates of all non‐fatal adverse events (the number of serious adverse events per person‐year) were similar in both groups (0.63 ± 1.56 events (intervention group) and 0.62 ± 1.48 events (control group); P > 0.20) for all comparisons, except for non‐fatal serious adverse events involving the gastrointestinal tract, which were more frequent in the intervention group (in 30 patients (0.05 events per person‐year) vs 17 patients (0.02 events per person‐year); P = 0.02). Another trial lists the total numbers and percentages of adverse events in the intervention group (12 (26%)) and in the control group (21 (43%)) and of serious adverse events in the intervention group (4 (9%)) and in the control group (3 (6%)).The other trials stated that researchers found no significant adverse effects of statins but did not report adverse events in detail. AUTHORS' CONCLUSIONS: A small number of trials providing low‐ or moderate‐quality evidence were suitable for inclusion in this review. They showed that use of statins resulted in a reduction in CRP and IL‐6, but that this did not translate into clear clinical benefit for people with COPD. Further randomised controlled trials are needed to explore this topic.

We present two cases of sinus pericranii (subgaleal varix). A term baby was found on newborn exam to have a small firm nodular swelling 1.5cm x 1.5cm in the occipito-parietal area with a small tuft of hair overlying the skin (figure 1). Figure 1 Visible sinus pericranii. An ultrasound scan confirmed a subcutaneous lesion, slightly to the right of the midline with a discrete vascular channel having transcranial extension and communicating with the …

Objectives To examine the effects of Ivacaftor on growth and pancreatic function in patients attending the Paediatric Cystic fibrosis (CF) Centre at Cork University Hospital. Methods A retrospective, convenience sampled cohort analysis was conducted in patients aged 2 to 17 with genetically confirmed CF (N=28, 15 male, 13 female). Subjects who received Ivacaftor over a 1 year period had an oral dose of either 75 or 150 mg twice daily depending on weight. Patients were excluded if concurrently taking Lumacaftor. The primary end points were estimated mean change from baseline through one year in pancrealipase (Creon) consumption per day and body mass index (BMI). Secondary end points included the changes in mean percent of predicted forced expiratory volume in 1 second (FEV1) as well as exocrine pancreatic marker faecal elastase-1 (FE-1) and random blood glucose within the Ivacaftor group. Results The change in pancrealipase use was significantly decreased in the Ivacaftor group in comparison to controls (1202± 587 IU/kg, p=0.039). In addition, Ivacaftor users had a significant increase in gross BMI (0.98± 0.51 kg/m2, p=0.010) and a non-significant increase in FEV1% predicted (10.9± 5.06%, p=0.123) in comparison to controls. On subgroup analysis, there was significant improvement in FE-1 after one year of Ivacaftor use (107± 80.8μg/g, p= 0.013, N=7). As well, there was mild decrease seen in random blood glucose, however this result was not significant (-0.43± 0.87 mmol/L, p=0.153, N=10). Conclusions Ivacaftor improves paediatric CF patients’ BMI, blood glucose, and FE-1 values while reducing their reliance on pancrealipase. This data supports previous research showing increasing lung function in Ivacaftor users. Subgroup analysis of those with serial FE-1 results revealed that 43% of those taking Ivacaftor reached pancreatic exocrine sufficiency (FE-1> 200μg/g). This implies that further study of Ivacaftor’s pancreatic implications is warranted. Similarly, prospective studies of new and emerging drugs of this class in a similar manner could yield positive results for patients.

Introduction Orkambi (Lumacaftor/Ivacaftor) was first introduced for use in the Cystic Fibrosis population in Ireland in 2017. It is only licensed for those patients who are homozygous for the F508del gene mutation.Orkambi was originally approved for children aged 12 years and older in 2017 and then this was extended for those aged 6–11 years old in 2018. Recently, the EMA(European Medicines Agency) has approved use for children 2–5 years. CUH(Cork University Hospital) looks after 98 paediatric patients with CF of whom 37 have been commenced on Orkambi since July 2017. Objectives The primary objective was to assess the outcomes of Orkambi at 6 and 12 months on FEV1, BMI and BMI Centile and to compare the days on Intravenous antibiotics and weeks of oral antibiotics for pulmonary exacerbations in the year before and after commencing Orkambi. Results Thirty seven patients were included in the study population with a split of 21 females and 16 males. The average profile of our patient cohort before commencing Orkambi was 11.0 years, BMI 16.8 kg/m2, BMI Centile 43.2 and Average FEV1 96.7%. To date, 11 patients have completed over a year of treatment and the remainder will have completed 12 months by June 2019. Six month followup has shown that 30/37(81%) of patients have had an increase in their BMI with an average BMI at 6 months of 17.5 and BMI difference of +0.7 kg/m2. BMI centile was increased in 24/37(65%) with centile difference of +5.7 to an average of 48.9. Lung function did not show any improvement from Pre-Orkambi values with average FEV1 of 95.9% at 6 months. This was also shown in followup of patients who completed 12 months of treatment with average FEV1 difference of -2%. For those who had completed 12 months on Orkambi, the no of weeks on oral antibiotics and IV antibiotics both showed a reduction in the year following commencement. There was a 26% decrease in oral antibiotics prescribed with average reduction of 1.5 weeks. Three patients had required IV antibiotics in the year prior. Two of these had no IVs over the following year and one patient with severe CF disease had a 55% reduction in days on IVs from 121 to 66 days. Conclusion Orkambi has improved BMI/BMI centiles but has not shown any improvement in FEV1. Preliminary data has shown a reduction in pulmonary exacerbations although further analysis of the remaining patients will allow more accurate conclusions.

Iatrogenic Cushing syndrome and secondary adrenal insufficiency due to intranasal steroids is rare in children. A 7 year old boy was referred to the paediatric endocrine clinic with suspected Cushing syndrome. He presented with excessive weight gain, marked striae and hypertension. His GP had performed a morning cortisol 99.6th centile); height 124.6 cm (50th-75th centile), body mass index (BMI) 30 kg/m2 (>99.6th centile) and blood pressure was 124/72 mmHg (>99th centile).The drug history was reviewed in detail by our Paediatric Pharmacist and revealed that over the past 20 months, he had been using betamethasone nasal drops continuously, prescribed at a dose of 2 drops, twice daily, into each nostril. A total of 38 repeat prescriptions had been dispensed and he had been taking double the prescribed amount per month. The duration of use (20 months) also far exceeded the recommended indication (4–6weeks max). Laboratory investigations: blood glucose 4.7 mmol/L, early morning cortisol Conclusion We describe a case of iatrogenic Cushing syndrome and adrenal insufficiency secondary to administration of long-term high-dose betamethasone nasal drops. Very few cases to date have been reported in the literature in children. Cushing syndrome caused by intranasal steroids is a rare event and more commonly occurs after oral or topical steroid use. Our patient was taking double the recommended dose for more than 20 months. Paediatricians must be aware of the complications of nasal steroid administration and long-term use should be avoided

BACKGROUND: People with cystic fibrosis face substantial physical, psychological, and social challenges as they move into adolescence and adulthood, which are likely to impact on their health-related quality of life. This study sought to examine the relative importance of physical and mental health variables associated with health-related quality of life in this group. METHODS: Adults and adolescents (N = 174; ≥14 y old) from across 11 adult or pediatric cystic fibrosis clinics in the Republic of Ireland, completed a background questionnaire that contained self-reported physical health variables, pulmonary function (ie, FEV1%) and body mass index. Questionnaire packs also contained the Hospital Anxiety and Depression Scale (HADS) and the Cystic Fibrosis Questionnaire-Revised, which has been specifically designed to assess health-related quality of life in patients with cystic fibrosis. RESULTS: HADS depression and/or anxiety scores were negatively associated with 11 of the 12 Cystic Fibrosis Questionnaire-Revised domain scores. FEV1% was positively associated with 8 domains when controlling for HADS anxiety but only 4 domains when controlling for HADS depression. HADS anxiety and depression scores demonstrated larger effect sizes and explained a greater proportion of the variance than pulmonary function in 8 of the 12 Cystic Fibrosis Questionnaire-Revised domain scores. CONCLUSIONS: Mental health variables, depression and anxiety, were strongly associated with health-related quality of life in subjects with cystic fibrosis and demonstrated greater effect sizes and explained a higher proportion of the variance overall than the physical health indicators, FEV1% and body mass index, which highlighted the importance of screening for, and treating, depression and anxiety symptoms.

Objective Screening for depression and anxiety in people with cystic fibrosis (CF) is recommended but this alone can miss the opportunity to assess and promote positive mental health and wellbeing. This cross-sectional study assessed positive mental health and wellbeing, and associations with physical health and health-related quality of life (HRQoL) in adults with CF. Methods Adults (n = 147) with CF from 9 CF centres in the Republic of Ireland completed the Warwick Edinburgh Mental Well-being scale, the Hospital Anxiety and Depression Scale and the Cystic Fibrosis Questionnaire-Revised. Demographic and physical health outcome data were also collected. Results High levels of positive mental health and wellbeing were reported in this sample. There were significant associations between positive ‘mental health and wellbeing’ and pulmonary function, self-reported physical health and recent hospitalizations. Positive mental health was significantly associated with 11 of the 12 CFQ-R domains assessing HRQoL. Conclusion Assessing and promoting positive mental health and wellbeing may contribute to improving or maintaining physical and mental health, and HRQoL in patients with cystic fibrosis. It provides valuable clinical information to complement depression and anxiety screening and has potential to track the effectiveness of mental health promotion strategies by assessing and monitoring positive mental health and wellbeing over time. Individuals with CF may benefit from interventions that promote positive mental health and wellbeing by enhancing coping and problem-solving skills and fostering hope and optimism. Future research should focus on the development and testing of positive mental health and wellbeing promotion interventions in people with CF.

Chronic respiratory infections are a leading global cause of morbidity and mortality. However, the molecular triggers that cause respiratory pathogens to adopt persistent and often untreatable lifestyles during infection remain largely uncharacterised. Recently, bile aspiration caused by gastro-oesophageal reflux (GOR) has emerged as a significant complication associated with respiratory disease, and cystic fibrosis (CF) in particular. Based on our previous finding that the physiological concentrations of bile influence respiratory pathogens towards a chronic lifestyle in vitro, we investigated the impact of bile aspiration on the lung microbiome of respiratory patients. Sputum samples (n = 25) obtained from a cohort of paediatric CF patients were profiled for the presence of bile acids using high-resolution liquid chromatography–mass spectrometry (LC-MS). Pyrosequencing was performed on a set of ten DNA samples that were isolated from bile aspirating (n = 5) and non-bile aspirating (n = 5) patients. Both denaturing gradient gel electrophoresis (DGGE) and pyrosequencing revealed significantly reduced biodiversity and richness in the sputum samples from bile aspirating patients when compared with non-aspirating patients. Families and genera associated with the pervasive CF microbiome dominated aspirating patients, while bacteria associated with the healthy lung were most abundant in non-aspirating patients. Bile aspiration linked to GOR is emerging as a major host trigger of chronic bacterial infections. The markedly reduced biodiversity and increased colonisation by dominant proteobacterial CF-associated pathogens observed in the sputum of bile aspirating patients suggest that bile may play a major role in disease progression in CF and other respiratory diseases. Electronic supplementary material The online version of this article (doi:10.1007/s10096-014-2133-8) contains supplementary material, which is available to authorized users.

Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease.

Background Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma. Objectives To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration. Search methods We searched the Cochrane Airways Group Asthma Trials Register until January 2015. Selection criteria We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals. Data collection and analysis Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible. Main results We included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events.A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less.There was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate-quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate-quality evidence).No statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate-quality evidence) and no statistically significant differences in overall risk of all-cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate-quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate-quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70). Authors' conclusions In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.

ObjectiveTo compare online and paper-based screening for depression and anxiety in adults with cystic fibrosis (CF).Design and settingCross-sectional study in CF clinics in Ireland and through the Cystic Fibrosis Ireland online community.Participants160 adult patients aged 18 or above were recruited. Of these, 147 were included in the analysis; 83 online and 64 paper-based. The remaining 13 were excluded because of incomplete data.MeasuresDepression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Data on pulmonary function (forced expiratory volume in 1 s %) and body mass index were self-reported based on clinical assessments. Sociodemographic data were collected.ResultsCompared with the paper-based participants, the online participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs 28.2 years) and were more likely to be married (32.5% vs 15.6%), living with their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs 15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and depression scores were not statistically different between online (P=0.83) and paper-based (P=0.92) participants based on Mann-Whitney U test. A significant negative correlation was found between depression and pulmonary function (r=−0.39, P=0.01) and anxiety and pulmonary function (r=−0.36, P=0.02). Based on Cronbach’s alpha, there were no statistically significant differences between the online and paper-based participants on the internal consistency of the HADS anxiety (P=0.073) and depression (P=0.378) scales.ConclusionsOur findings suggest that online and paper-based screening for depression and anxiety in adult patients with CF yield comparable findings on prevalence rates and scores, associations with health and internal consistency of subscales. This study highlights that online screening offers an alternative method to paper-based screening. Further research with a larger sample and assessment of measurement equivalence between online and paper based screening is needed to confirm our results.

Background Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted. Objectives To assess the effects of self-management education interventions on improving health outcomes for patients with cystic fibrosis and their caregivers Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register (date of the last search: 22 August 2013). We also searched databases through EBSCO (CINAHL; Psychological and Behavioural Sciences Collection; PsychInfo; SocINDEX) and Elsevier (Embase) and handsearched relevant journals and conference proceedings (date of the last searches: 01 February 2014 ). Selection criteria Randomised controlled trials, quasi-randomised controlled trials or controlled clinical trials comparing different types of self-management education for cystic fibrosis or comparing self-management education with standard care or no intervention. Data collection and analysis Two authors assessed trial eligibility and risk of bias. Three authors extracted data. Main results Four trials (involving a total of 269 participants) were included. The participants were children with cystic fibrosis and their parents or caregivers in three trials and adults with cystic fibrosis in one trial. The trials compared four different self-management education interventions versus standard treatment: (1) a training programme for managing cystic fibrosis in general; (2) education specific to aerosol and airway clearance treatments; (3) disease-specific nutrition education; and (4) general and disease-specific nutrition education. Training children to manage cystic fibrosis in general had no statistically significant effects on weight after six to eight weeks, mean difference -7.74 lb (i.e. 3.51 kg) (95% confidence interval -35.18 to 19.70). General and disease-specific nutrition education for adults had no statistically significant effects on: pulmonary function (forced expiratory volume at one second), mean difference -5.00 % (95% confidence interval -18.10 to 8.10) at six months and mean difference -5.50 % (95% confidence interval -18.46 to 7.46) at 12 months; or weight, mean difference - 0.70 kg (95% confidence interval -6.58 to 5.18) at six months and mean difference -0.70 kg (95% confidence interval -6.62 to 5.22) at 12 months; or dietary fat intake scores, mean difference 1.60 (85% confidence interval -2.90 to 6.10) at six months and mean difference 0.20 (95% confidence interval -4.08 to 4.48) at 12 months. There is some limited evidence to suggest that self-management education may improve knowledge in patients with cystic fibrosis but not in parents or caregivers. There is also some limited evidence to suggest that self-management education may result in positively changing a small number of behaviours in both patients and caregivers. Authors' conclusions The available evidence from this review is of insufficient quantity and quality to draw any firm conclusions about the effects of self-management education for cystic fibrosis. Further trials are needed to investigate the effects of self-management education on a range of clinical and behavioural outcomes in children, adolescents and adults with cystic fibrosis and their caregivers.

Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next-generation sequencing to identify the causative mutation for autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish Traveller family. We identified a double-nucleotide polymorphism (g.1157G>A and g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients. The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB patients, including one individual with Matthew-Wood syndrome (MWS; MCOPS9). STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process essential to eye development and growth. We have shown that the G304K mutant STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity. Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels account for the eye malformations in STRA6 p.G304K patients. The current study demonstrates that STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS.

Background Long-acting inhaled s2-adrenergic agonists (LABAs) are recommended as 'add-on' medication to inhaled corticosteroids (ICS) 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 LABAs to ICS in patients insufficiently controlled on ICS alone. Search methods 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 May 2008. Selection criteria We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults. Data collection and analysis Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events. Main results Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 µg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and 38%. Studies recruiting adults dominated the analysis (6203 adult participants versus 605 children). The subgroup estimate for paediatric studies was not statistically significant (RR 0.89, 95% CI 0.58 to 1.39) and includes the possibility of the superiority of ICS alone in children. Higher than usual dose of LABA was associated with significantly less benefit. The difference in the relative risk of serious adverse events with LABA was not statistically significant from that of ICS alone (RR 1.06, 95% CI 0.87 to 1.30). The addition of LABA led to a significantly greater improvement in FEV1 (0.11 litres, 95% 0.09 to 0.13) and in the proportion of symptom-free days (11.88%, 95% CI 8.25 to 15.50) compared to ICS monotherapy. It was also associated with a reduction in the use of rescue short-acting s2-agonists (-0.58 puffs/day, 95% CI -0.80 to -0.35), fewer withdrawals due to poor asthma control (RR 0.50, 95% CI 0.41 to 0.61), and fewer withdrawals due to any reason (RR 0.80, 95% CI 0.75 to 0.87). There was no statistically significant group difference in the risk of overall adverse effects (RR 1.00, 95% 0.97 to 1.04), withdrawals due to adverse health events (RR 1.04, 95% CI 0.86 to 1.26) or any of the specific adverse health events. Authors' conclusions In adults who are symptomatic on low to high doses of ICS monotherapy, the addition of a LABA at licensed doses reduces the rate of exacerbations requiring oral steroids, improves lung function and symptoms and modestly decreases use of rescue short-acting s2-agonists. In children, the effects of this treatment option are much more uncertain. The absence of group difference in serious adverse health events and withdrawal rates in both groups provides some indirect evidence of the safety of LABAs at usual doses as add-on therapy to ICS in adults, although the width of the confidence interval precludes total reassurance.

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 s2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. Objectives To determine the effect of the combination of long-acting s2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the risk of asthma exacerbations, pulmonary function and on other measures of asthma control, and to look for characteristics associated with greater benefit for either treatment option. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs, clinical trial registries and correspondence with manufacturers until May 2008. Selection criteria RCTs that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children and adults with asthma. Data collection and analysis Two authors independently assessed methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the number of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Main results This review included 48 studies (15,155 participants including 1155 children and 14,000 adults). Participants were inadequately controlled on their current ICS regimen, experiencing ongoing symptoms and with generally moderate (FEV1 60% to 79% of predicted) airway obstruction. The studies tested the combination of salmeterol or formoterol with a median dose of 400 mcg/day of beclomethasone or equivalent (BDP-eq) compared to a median of 1000 mcg/day of BDP-eq, usually for 24 weeks or less. There was a statistically significantly lower risk of exacerbations requiring systemic corticosteroids in patients treated with LABA and ICS (RR 0.88, 95% CI 0.78 to 0.98, 27 studies, N = 10,578) from 11.45% to 10%, with a number needed to treat of 73 (median study duration: 12 weeks). The study results were dominated by adult studies; trial data from three paediatric studies showed a trend towards increased risk of rescue oral steroids (RR 1.24, 95% CI 0.58 to 2.66) and hospital admission (RR 2.21, 95% CI 0.74 to 6.64) associated with combination therapy. Overall, there was no statistically significant difference in the risk ratios for either hospital admission (RR 1.02, 95% CI 0.67 to 1.56) or serious adverse events (RR 1.12, 95% CI 0.91 to 1.37). The combination of LABA and ICS resulted in significantly greater but modest improvement from baseline in lung function, symptoms and rescue medication use than with higher ICS dose. Despite no significant group difference in the risk of overall adverse events (RR 0.99, 95% CI 0.95 to 1.03), there was an increase in the risk of tremor (RR 1.84, 95% CI 1.20 to 2.82) and a lower risk of oral thrush (RR 0.58, 95% CI 0.40 to 0.86)) in the LABA and ICS compared to the higher ICS group. There was no significant difference in hoarseness or headache between the treatment groups. The rate of withdrawals due to poor asthma control favoured the combination of LABA and ICS (RR 0.65, 95% CI 0.51 to 0.83). Authors' conclusions In adolescents and adults with sub-optimal control on low dose ICS monotherapy, the combination of LABA and ICS is modestly more effective in reducing the risk of exacerbations requiring oral corticosteroids than a higher dose of ICS. Combination therapy also led to modestly greater improvement in lung function, symptoms and use of rescue s2 agonists and to fewer withdrawals due to poor asthma control than with a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor and less oral candidiasis with combination therapy, the two options appear relatively safe in adults although adverse effects associated with long-term ICS treatment were seldom monitored. In children, combination therapy did not lead to a significant reduction, but rather a trend towards an increased risk, of oral steroid-treated exacerbations and hospital admissions. These trends raised concern about the safety of combination therapy in view of modest improvement in children under the age of 12 years.

Consensus statements recommend the addition of long-acting inhaled ss2-agonists (LABA) only in asthmatic patients who are inadequately controlled on inhaled corticosteroids (ICS). It is not uncommon for some patients to be commenced on ICS and LABA together as initial therapy.To compare the efficacy of combining inhaled corticosteroids with long-acting ss2-agonists (ICS+LABA) with inhaled corticosteroids alone (ICS alone) in steroid-naive children and adults with persistent asthma. We assessed two protocols: (1) LABA + ICS versus a similar dose of ICS (comparison 1) and (2) LABA + ICS versus a higher dose of ICS (comparison 2).We identified randomised controlled trials through electronic database searches (May 2008).Randomised trials comparing ICS + LABA with ICS alone in children and adults with asthma who had no inhaled corticosteroids in the preceding 28 days prior to enrolment.Each author assessed studies independently for risk of bias and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was rate of patients with one or more asthma exacerbations requiring rescue systemic corticosteroids. Results are expressed as relative risks (RR) for dichotomous data and as mean differences (MD) or standardised mean differences (SMD) for continuous data.Twenty-eight study comparisons drawn from 27 trials (22 adult; five paediatric) met the review entry criteria (8050 participants). Baseline data from the studies indicated that trial populations had moderate or mild airway obstruction (FEV1/=65% predicted), and that they were symptomatic prior to randomisation. In comparison 1, the combination of ICS and LABA was not associated with a significantly lower risk of patients with exacerbations requiring oral corticosteroids (RR 1.04; 95% confidence interval (CI) 0.73 to 1.47) or requiring hospital admissions (RR 0.38; 95% CI 0.09 to 1.65) compared to a similar dose of ICS alone. The combination of LABA and ICS led to a significantly greater improvement from baseline in FEV1 (0.12 L/sec; 95% CI 0.07 to 0.17), in symptoms (SMD -0.26; 95% CI -0.37 to -0.14) and in rescue ss2-agonist use (-0.41 puffs/day; 95% CI -0.73 to -0.09) compared with a similar dose of ICS alone. There was no significant group difference in the risk of serious adverse events (RR 1.15; 95% CI 0.64 to 2.09), any adverse events (RR 1.02; 95% CI 0.96 to 1.09), study withdrawals (RR 0.95; 95% CI 0.82 to 1.11), or withdrawals due to poor asthma control (RR 0.94; 95% CI 0.63 to 1.41).In comparison 2, the combination of LABA and ICS was associated with a higher risk of patients requiring oral corticosteroids (RR 1.24; 95% CI 1 to 1.53) and study withdrawal (RR 1.31; 95% CI 1.07 to 1.59) than a higher dose of ICS alone. For every 100 patients treated over 43 weeks, nine patients using a higher dose ICS compared to 11 (95% CI 9 to 14) on LABA and ICS suffered one or more exacerbations requiring rescue oral corticosteroids. There was a high level of statistical heterogeneity for FEV1 and morning peak flow. There was no statistically significant group difference in the risk of serious adverse events. Due to insufficient data we could not aggregate results for hospital admission, symptoms and other outcomes.In steroid-naive patients with mild to moderate airway obstruction, the combination of ICS and LABA does not significantly reduce the risk of patients with exacerbations requiring rescue oral corticosteroids over that achieved with a similar dose of ICS alone. However, it significantly improves lung function, reduces symptoms and marginally decreases rescue ss2-agonist use. Initiation of a higher dose of ICS is more effective at reducing the risk of exacerbations requiring rescue systemic corticosteroids, and of withdrawals, than combination therapy. Although children appeared to respond similarly to adults, no firm conclusions can be drawn regarding combination therapy in steroid-naive children, given the small number of children contributing data.

BACKGROUND: Long‐acting beta(2)‐agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma. OBJECTIVES: To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration. SEARCH METHODS: We searched the Cochrane Airways Group Asthma Trials Register until January 2015. SELECTION CRITERIA: We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible. MAIN RESULTS: We included in this review a total of 33 trials representing 39 control‐intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS. LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV(1)) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies. There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate‐quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate‐quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate‐quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low‐quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV(1) (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low‐quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD ‐0.07 puffs/d, 95% CI ‐0.11 to ‐0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD ‐0.08 puffs/d, 95% CI ‐0.13 to ‐0.03, three studies, 672 children). No significant group difference was noted in exercise‐induced % fall in FEV(1), symptom‐free days, asthma symptom score, quality of life, use of reliever medication and adverse events. A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV(1) was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less. There was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate‐quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate‐quality evidence). No statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate‐quality evidence) and no statistically significant differences in overall risk of all‐cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate‐quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate‐quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70). AUTHORS' CONCLUSIONS: In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.

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.