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14, 95% confidence interval [CI] 1.41-7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36-6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was below 15% versus 10% would result in fewer patients remaining on the same ICS dose (40/384, 10.4% versus 141/384, 36.7%) but similar proportions of patients avoiding exacerbations (222/243, 91.4%, 95% CI 87.1%-94.6% versus 311/344, 90.4%, 95% CI 86.8%-93.3%). CONCLUSION In patients with mild-to-moderate asthma, gradual ICS reduction when FeNO is less then 50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations. Copyright ©ERS 2020.RATIONALE Early-life antibiotic use has been associated with development of atopic diseases, but the aetiology remains unclear. To elucidate aetiology, we used a discordant twin design to control for genetic and environmental confounding. METHODS We conducted a retrospective cohort study in twins (3-10 years) from the Netherlands Twin Register (NTR, n=34 352) and a replication study at age 9 in the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7906). Antibiotic use was recorded at 0-2 years. Doctor diagnosed asthma and eczema were reported by parents when children were 3-12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs. RESULTS Early-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34 95%CI 1.28-1.41; CATSS 1.45 95%CI 1.34-1.56) and eczema (NTR OR 1.08 95%CI 1.03-1.13; CATSS 1.07 95%CI 1.01-1.14) in unmatched analyses. Co-twin analyses in mono- and dizygotic twin pairs showed similar results for asthma (NTR 1.54 95%CI 1.20-1.98 and CATSS 2.00 95%CI 1.28-3.13), but opposing results for eczema in NTR (0.99 95%CI 0.80-1.25) and CATSS (1.67 95%CI 1.12-2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS 1.45 95%CI 1.34-1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS 1.02 95%CI 0.88-1.17). CONCLUSION Children exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed, when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors. Copyright ©ERS 2020.INTRODUCTION Sarcoidosis associated pulmonary hypertension (SAPH) is associated with reduced survival in single center studies. An international registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. METHODS ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrollment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest x-ray Scadding stage, 6 min walk distance (6MWD) among others. Cox regression models were used to identify independent predictors of transplant-free survival. RESULTS Data from a total of 215 patients followed for a mean of 2.5±1.9 years were available for analysis. In the 159 pre-capillary patients the 1, 3 and 5 year transplant free survival was 98.2.1%, 78.2% and 71.2%, respectively. Incident group 83.5%, 70.3% and 58.3% and prevalent group 94.7%, 72.2%, 66.3% 1,3 and 5 year survival, respectively. Patients with reduced DLCO and 6MWD less then 300 m in the pre-capillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved FEV1/FVC ratio were identified as independent risk factors for reduced transplant-free survival in the pre-capillary cohort. CONCLUSION Reduced diffusion capacity and 6MWD less then 300 m at the time of registry enrollment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was also identified as an independent risk factor for worsened outcomes. Copyright ©ERS 2020.Severe asthma is a high burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control [median Asthma Control Questionnaire (ACQ)-5 score of 3.4], frequent exacerbations [median 3 courses of oral corticosteroids (OCS) in the previous 12 months], and 47% required daily OCS. Meclofenamate Sodium Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared to the previous year (annualised rate ratio 0.34 [95% CI 0.29-0.41], p less then 0.001) and hospitalisations (rate ratio 0.46 [95% CI 0.33-0.63], p less then 0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting. Copyright ©ERS 2020.BACKGROUND Accelerated lung function decline in individuals with cystic fibrosis (CF) starts in adolescence with respiratory complications being the most common cause of death in later life. Factors contributing to lung function decline are not well understood, in particular its relationship with structural lung disease in early childhood. Detection and management of structural lung disease could be an important step in improving outcomes in CF patients. METHODS Annual chest computed tomography (CT) scans were available from 2005 to 2016 as a part of AREST CF cohort for children aged 3-months to 6-years. Annual spirometry measurements were available for 89.77% of the cohort (n=167 children at age 5-6 years) from ages 5 to 15 years through outpatient clinics at Perth Children's Hospital and The Royal Children's Hospital in Melbourne. (n=697 measurements, age 9.3 (2.1) years). FINDINGS Children with a total CT score at 5-6 years above the median were more likely to have abnormal FEV1 (aHR 2.67 (1.06, 6.72) p=0.