Treating nontuberculous mycobacteria in children with cystic fibrosis: a multicentre retrospective study.

BACKGROUND: Respiratory infection with nontuberculous mycobacteria (NTM) in children with cystic fibrosis (CF) has increased in prevalence. The condition is difficult to diagnose and treatments are complex with limited evidence to guide practice. This study describes the approaches to diagnosis, management and consequences of treatment in a multicentre cohort of children with CF in the UK. METHODS: Retrospective data were collected from 11 CF specialist centres from patients less than 17 years old, treated for NTM infection between 2006 and 2017. Descriptive statistics were used to describe the clinical characteristics of children treated. Treatment regimens, adverse events and success of treatment, with respect to lung function and culture conversion, were evaluated. RESULTS: Data from 70 patients treated for NTM pulmonary disease were collated (60 Mycobacterium abscessus complex (MABSC); 10 M. avium complex (MAC)). Older age and previous diagnosis of allergic bronchopulmonary aspergillosis were all significantly associated with NTM. There was a wide variance in drug choice and side effects were reported with all agents. NTM eradication occurred in 80% of patients with MAC and 48% with MABSC, with variable outcomes on lung function. CONCLUSIONS: Diagnosis and treatment of NTM infection in children with CF is challenging. Treatment success is not guaranteed, particularly for MABSC. Large clinical trials are urgently required to evaluate treatment regimes and their suitability and efficacy in children.

Assessing the impact of breathing retraining on asthma symptoms and dysfunctional breathing in children.

OBJECTIVE: To assess the impact of breathing retraining on asthma symptoms and dysfunctional breathing (DB) in children. Breathing retraining can improve DB but there is a lack of evidence in pediatrics. METHODS: Participants attended outpatient physiotherapy appointments and received individually tailored interventions, particularly Buteyko breathing techniques. The primary outcome was the change in the Asthma Control Test (ACT) score or change in childhood ACT (CACT) score from first to final appointment. The ACT and CACT are validated in children more than or equal to 12 years and children aged 4 to 11, respectively. The secondary outcome measure was the change in Nijmegen Questionnaire (NQ) score from first to the final appointment (score range, 0-64) with a score of more than or equal to 23 indicating DB symptoms. RESULTS: One hundred and sixty-nine children with asthma attended and completed a mean of six physiotherapy sessions, over a mean of 15 weeks. Patients were aged 2 to 18, mean 10 years. Fifty-five patients were more than or equal to 12 years old and 114 were less than or equal to 11 years. One hundred and seven patients were receiving BTS/SIGN asthma guideline step 1 to 3 therapy and 62 were on step 4 to 5 therapy. The mean ACT score improved by 4.4 (P < 0.0001), the mean CACT score improved by 4.9 (P < 0.0001), and the mean NQ score change improved by -9.3 points (P < 0.0001). CONCLUSION: In addition to standard medical therapy, individually tailored physiotherapy interventions improved asthma control and DB in children on all levels of asthma treatment. A randomized controlled study is required to determine whether these improvements are due to the intervention.

Optimizing the Dosing of Intravenous Theophylline in Acute Severe Asthma in Children.

Optimizing the management of children presenting with acute severe asthma is of utmost importance to minimize hospital stays, morbidity, and mortality. Intravenous medications, including theophyllines, are used as second-line treatments for children experiencing a life-threatening exacerbation. For intravenous theophylline (aminophylline), guidelines and formularies recommend a target therapeutic range between 10 and 20 mg/l, with the commonest regimen being a loading dose of 5 mg/kg followed by an infusion calculated by age and weight. This review assesses the evidence underpinning these recommendations, highlighting the shortcomings in our understanding of the association between serum concentrations achieved, dose given, and clinical improvement experienced. To close the knowledge gap and improve outcomes for children presenting with acute severe asthma, we propose a series of research strategies to improve the assessment of illness severity, ascertain the optimal dose to maximize benefit and minimize risk, prospectively collect adverse events, and to better understand the inter-individual variation in responses to treatments.

The B lymphocyte differentiation factor (BAFF) is expressed in the airways of children with CF and in lungs of mice infected with Pseudomonas aeruginosa.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection. METHODS: BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue. RESULTS: BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection. CONCLUSIONS: In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective.