Purpose of review Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed. Recent findings Adherence monitoring using electronic devices has shown that only 20–30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6–11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain. Summary Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.

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contacts, migrants from high prevalence countries and those who are immunosuppressed. The risk of hepatotoxicity in treating LTBI is thought to be low but much of this evidence is in patients treated with 6 months of isoniazid (6H) rather than 3 months of rifampicin and isoniazid (3RH). Equally, other than age, there is limited data on other factors which may contribute to the risk of developing hepatotoxicity. Methods A retrospective study was performed at our centre. We analysed all patients treated with chemoprophylaxis, regardless of indication, between 2009 and 2013. Demographic data, treatment regimens and adverse drug reactions, including hepatotoxicity, were recorded. Severe hepatotoxicity was defined as either a rise in ALT five times greater than the upper limit of normal, or as any change in liver function that required an interruption or alteration in treatment. Liver function tests (LFTs) were routinely measured at baseline and then again at two weeks. Results 290 cases were identified. 84.5% of patients were treated with 3RH, 12.1% were treated with 6H. 2.1% experienced severe hepatotoxicity 2 weeks into treatment. None had symptoms which prompted blood tests prior to our standard 2 week LFTs. Gender, age, documented co-existing liver disease, regimen choice, concomitant use of hepatotoxic drugs and reason for giving chemoprophylaxis were not significantly associated with an increased risk of hepatotoxicity. LTBI treatment was case managed by TB nurses with 91.7% of patients successfully completing treatment. There was no significant difference in treatment completion or adherence rates in those who developed hepatotoxicity compared with those who did not. Conclusions Our review demonstrates a low incidence of hepatotoxicity associated with treatment of LTBI and highlights the difficulty in predicting those in whom it will occur. If management of LTBI moves from primary to secondary care it will remain important to perform LFTs at two weeks. Objectives To interrogate the UK national data set and explore longitudinal relationships between FEV1, HbA1c and OGTT parameters in young people with CF up to the age of 23 years. Methods The UK CF data set (2007 to 2012) recording annual measurements of height, weight, BMI,% predicted FEV1 and FVC, HbA1c and 2 h glucose (2 hrGlu) (>10 years only) was interrogated. HbA1c values >6.5% and 5.7-6.5% were used to define 'undiagnosed' diabetes and a pre-diabetic state respectively in patients not labelled as having CFRD. Data from cases with known CFRD were censored. Longitudinal models analysed %FEV1 and %FVC as dependent variables and HbA1c or 2 hrGlu, BMI SDS and age as covariates in patients with HbA1c in the pre-diabetic range. Results 2105 patients (1097 males), 87.9% with DF508 mutations, median (range) age 13.7 (5.6-22) years, mean (SD) BMI Z score -0.11+/-1.1, %FEV1 82.1+/-20.3 at first visit were included. Median range follow up was 3 (1-5) years. 2 hrGlu was available in a subgroup (n = 636). Median HbA1c (Table 1) but not 2 hrGlu (slope -0.1, p = 0.3), ...

contacts, migrants from high prevalence countries and those who are immunosuppressed. The risk of hepatotoxicity in treating LTBI is thought to be low but much of this evidence is in patients treated with 6 months of isoniazid (6H) rather than 3 months of rifampicin and isoniazid (3RH). Equally, other than age, there is limited data on other factors which may contribute to the risk of developing hepatotoxicity. Methods A retrospective study was performed at our centre. We analysed all patients treated with chemoprophylaxis, regardless of indication, between 2009 and 2013. Demographic data, treatment regimens and adverse drug reactions, including hepatotoxicity, were recorded. Severe hepatotoxicity was defined as either a rise in ALT five times greater than the upper limit of normal, or as any change in liver function that required an interruption or alteration in treatment. Liver function tests (LFTs) were routinely measured at baseline and then again at two weeks. Results 290 cases were identified. 84.5% of patients were treated with 3RH, 12.1% were treated with 6H. 2.1% experienced severe hepatotoxicity 2 weeks into treatment. None had symptoms which prompted blood tests prior to our standard 2 week LFTs. Gender, age, documented co-existing liver disease, regimen choice, concomitant use of hepatotoxic drugs and reason for giving chemoprophylaxis were not significantly associated with an increased risk of hepatotoxicity. LTBI treatment was case managed by TB nurses with 91.7% of patients successfully completing treatment. There was no significant difference in treatment completion or adherence rates in those who developed hepatotoxicity compared with those who did not. Conclusions Our review demonstrates a low incidence of hepatotoxicity associated with treatment of LTBI and highlights the difficulty in predicting those in whom it will occur. If management of LTBI moves from primary to secondary care it will remain important to perform LFTs at two weeks. Objectives To interrogate the UK national data set and explore longitudinal relationships between FEV1, HbA1c and OGTT parameters in young people with CF up to the age of 23 years. Methods The UK CF data set (2007 to 2012) recording annual measurements of height, weight, BMI,% predicted FEV1 and FVC, HbA1c and 2 h glucose (2 hrGlu) (>10 years only) was interrogated. HbA1c values >6.5% and 5.7-6.5% were used to define 'undiagnosed' diabetes and a pre-diabetic state respectively in patients not labelled as having CFRD. Data from cases with known CFRD were censored. Longitudinal models analysed %FEV1 and %FVC as dependent variables and HbA1c or 2 hrGlu, BMI SDS and age as covariates in patients with HbA1c in the pre-diabetic range. Results 2105 patients (1097 males), 87.9% with DF508 mutations, median (range) age 13.7 (5.6-22) years, mean (SD) BMI Z score -0.11+/-1.1, %FEV1 82.1+/-20.3 at first visit were included. Median range follow up was 3 (1-5) years. 2 hrGlu was available in a subgroup (n = 636). Median HbA1c (Table 1) but not 2 hrGlu (slope -0.1, p = 0.3), ...