F. Frost

What’s hot that the other lot got

Ivacaftor is a cystic fibrosis transmembrane receptor (CFTR)-directed treatment for people with cystic fibrosis (CF) and a G551D mutation (approximately 5% of the CF population). Treatment results in significant clinical benefits; however, the effects on the pulmonary microbiome are less well understood. Hisert et al ( Am J Respir Crit Care Med 2017;195:1617–28) prospectively studied 12 subjects as they were initiated on ivacaftor. Sputum was collected at multiple times in the first week of treatment and then regularly for over 2u2009years. Airway inflammatory profile, P. aeruginosa sputum counts, quantitative PCR and changes in the 16S microbiome were all investigated. Rapid and significant reductions in the sputum inflammatory cytokines interleukin (IL)-8, IL-1B and neutrophil elastase were observed during the first week of treatment and continued to decrease over the subsequent 24-month follow-up. P. aeruginosa counts showed a 10-fold reduction (−1.67 log10 CFU/mL, 95%u2009CI −2.39 to −0.96; …

Ghost of chest drain past

A 20-year-old woman with recurrent left-sided pneumothoraces underwent video-assisted thoracoscopic pleurectomy and wedge resection of a left apical bulla. Medical history included ABCA3 pulmonary surfactant dysfunction and subsequent interstitial lung disease with diffuse ground glass changes suggestive of a desquamative interstitial pneumonitis (DIP). She was a lifelong non-smoker. Spirometry revealed forced vital capacity 0.97 L, 32% predicted and carbon monoxide transfer factorxa0(TLCO) 27% predicted. The operation was uneventful but there was a persistent postoperative air leak requiring prolonged pleural drainage but no other intervention. …

Cystic fibrosis related diabetes is not independently associated with increased Stenotrophomonas maltophilia infection: Longitudinal data from the UK CF Registry

INTRODUCTIONnStenotrophomonas maltophilia is common in the sputum of people with cystic fibrosis related diabetes (CFRD), raising the question as to whether this is a risk factor for its acquisition. We investigated this at a population level.nnnMETHODSnWe analysed national Cystic Fibrosis Registry data 2011-2015 for 8047 people with CFu202f>u202fage 6u202fyears, looking at demographics, diagnosis of CFRD, lung function and sputum microbiology; using descriptive and multivariate strategies to establish independent predictors for S. maltophilia culture and associated outcomes.nnnRESULTSnS. maltophilia was present in 1148 (14.1%). Although univariate analysis confirmed it was more prevalent in those with CFRD, when adjusted for other clinical parameters there was no longer a relationship. Markers of more severe lung disease were independent risk-factors for S. maltophilia.nnnCONCLUSIONnAlthough S. maltophilia is more common in people with CFRD, it is not an independent risk-factor for S. maltophilia acquisition.

Continuous glucose monitoring guided insulin therapy is associated with improved clinical outcomes in cystic fibrosis-related diabetes

INTRODUCTIONnContinuous glucose monitoring (CGM) allows assessment of day to day glycaemic excursions and detects early glucose handling abnormalities that may not be apparent on oral glucose tolerance testing (OGTT). However, there is little published evidence as to whether these early dysglycaemic changes are amenable to treatment. We present outcomes following CGM guided insulin initiation at our centre.nnnMETHODSnAdults without a prior diagnosis of cystic fibrosis related diabetes (CFRD) whom underwent >72u202fh CGM at our adult CF centre were included in the study. Clinical outcomes including weight and pulmonary function changes over the next 12u202fmonths were compared between groups based on CGM results and subsequent management.nnnRESULTSnCGM profiles for 59 patients were analysed. Insulin was commenced in 37 patients who had evidence of hyperglycaemia on CGM. Significant improvements in mean [95% confidence intervals] forced expiratory volume in 1u202fs (FEV1) (+4.3% predicted [1.06-7.48], pu202f=u202f0.01) and weight (+1.2u202fkg [0.32-2.15], pu202f=u202f0.01) were observed at 3u202fmonths in the insulin group. Annual rate of pulmonary function decline was also improved following insulin initiation.nnnCONCLUSIONnInsulin treatment targeted towards glycaemic excursions seen on CGM is associated with improvements in lung function and weight with subsequent reduced pulmonary function decline.

Case Report: First report of Elizabethkingia miricola infection in a patient with cystic fibrosis

Elizabethkingia miricola is a rare non-fermenting Gram-negative rod that has previously been reported to be associated with blood stream and pulmonary abscess infections, but never before in cystic fibrosis (CF). Here we present the first reported case of Elizabethkingia miricola infection in a patient with CF and discuss the management options. We describe a patient with CF in whom we observed clinical and spirometric evidence of pulmonary exacerbation with the associated growth of E. miricola in sputum culture. The period of clinical instability was observed to coincide with the obtainment of four sputum samples from which E. miricola was cultured; improvement was seen following treatment with ciprofloxacin and the subsequent eradication of E. miricola. We conclude that E. miricola is able to survive in the CF lung and in this case was associated with pulmonary exacerbation. Empirical treatment with fluoroquinolones is appropriate, based on our experience.

Case Report: Haemolytic anaemia with ceftazidime use in a patient with cystic fibrosis

Drug-induced Immune Haemolytic Anaemia (DIIHA) is a rare but serious complication of cephalosporin use. Ceftazidime is recognized to be a rare cause of DIIHA. We report and discuss a case of DIIHA in a person with cystic fibrosis who developed severe haemolytic anaemia following use of ceftazidime in the management of an acute pseudomonal pulmonary exacerbation.

Pulmonary function testing is safe in patients with thoracic aortic aneurysms

Thoracic aortic aneurysms (TAA) occur in up to 16 patients per 100u200a000 of the population and are increasingly amenable to surgical correction [1]. However, low lung function is associated with poor post-operative outcomes, and a pre-operative assessment of pulmonary function is therefore important for prognostication [2]. Spirometry is safe as part of pre-operative work-up in patients with thoracic aortic aneurysms http://ow.ly/uwSe30lJ6Qn

Between a Rock and an Airspace: Pneumothorax After Extracorporeal Shock Wave Lithotripsy for Renal Stones in a Patient With Cystic Fibrosis

Renal disease is a well-recognized manifestation of cystic fibrosis (CF) and people with CF are at increased risk of nephrolithiasis. Lithotripsy is the preferred treatment but has occasionally been associated with pulmonary complications. Here we report the case of a person with CF who developed a pneumothorax soon after lithotripsy and discuss the potential mechanism of injury. We hope this case highlights some of the additional considerations clinicians should take into account when managing patients with advanced pulmonary disease in CF.

P244 Extended cftr screening for patients with a clinical diagnosis of cf but only one gene on initial screening

Introduction Standard CF genotyping only identifies 94% of CF genes, resulting in the emergence of a “cystic fibrosis screen positive, inconclusive diagnosis” (CFSPID) designation. This, and the advent of genotype-specific CFTR directed therapies has highlighted the need for more comprehensive genotyping, particularly to identify rarer genes when only a single gene is found on initial screening. However, extended CFTR screening is an expensive investigation and we wished to assess its use and yield. Methods Between 2014 and 2016 we identified 40 people with CF attending our large regional adult unit without two known pathogenic CFTR genes and offered them extended CFTR screening. We looked at the yield in terms of additional genes identified and their clinical significance in 37 of these (3 refused/did not attend). Results A new molecular diagnosis (i.e., two pathogenic genes) was made in 18 (48.5%) people with CF. Genes associated with CFTR related disorders were found in a further 2 (5.5%), genes of uncertain pathogenicity were found in 3 (8.1%), and one or no genes were found in 14 (37.8%). Of the 18 people with CF with additional identified genes, 8 had those associated with responsiveness to the CFTR potentiator ivacaftor (4 × 3272–26 A≥G, 1 × 711+3 A≥G, 1 × R347H, 1 × 2789+5G≥A, 1 × S945L) and 2 of these (R347H and S945L) have recently been approved for ivacaftor use by the U.S. Food and Drug Administration. Conclusions In people with a clinical diagnosis of CF but only one pathogenic gene on initial screen, extended CFTR screening identified a second gene in nearly half of cases. Furthermore, a significant proportion of the identified genes have been reported to respond to ivacaftor. It is therefore important that all people with CF without two known mutations undergo extended mutation screening in order to establish who may benefit should the current license for ivacaftor be expanded in the UK.

P248 Cfrd is not an independent risk factor for stenotrophomonas maltophilia acquisition – 5 year analysis of uk cf registry data

Introduction Recently, Stenotrophomonas maltophilia (SM) has been shown to have an increased prevalence in the sputum of people with CF-related diabetes (CFRD), raising the question as to whether CFRD is a risk factor for its acquisition. We investigated this at a population level by looking at UK CF Registry data. Methods We analysed national UK CF Registry data for 2011–2015, looking at demographics, lung function and sputum microbiology, using descriptive and multivariable strategies to establish independent predictors for SM culture and associated outcomes. 6234 people with CF older than age 12 (mean 26 years, CFRD 26%, SM 15%, 54% male) with more than 3 years complete sputum microbiology and lung function data were included. Results Although on univariate analysis those with SM were more likely to have CFRD (odds ratio [95%u2009CI] 1.18 [1.01–1.39]u2009p<0.0001), lower lung function (mean FEV1 [% predicted] 66.6 vs. 74.15, p<0.001) and more IV days (24 vs. 10, p<0.0001), multivariate logistic regression analysis showed no independent association for CFRD or Hba1c but IV antibiotic use and Aspergillus culture independently demonstrated an increased likelihood of SM growth (see Table 1). Furthermore, longevity of SM growth showed weak but statistically significant correlations with poorer FEV1 (rho −0.2, p<0.0001) and more IV days (rho=0.1, p<0.0001) but no association with CFRD (OR 1.09 [0.98–1.21]) or Hba1c (rho=-0.001, p=0.94). Abstract P248 Table 1 Multivariate analysis of potential predictors of SM growth Variable Odds Ratio (95%u2009CI) Age (years) >18 0.99 (0.98–1.00) NS FEV1 (% predicted) <50<30 1.22 (0.92–1.64)1.28 (0.82–2.01) NSNS IV antibiotics (days/year) 0>0>14 0.41 (0.31–0.52)1.46 (1.05–2.02)1.64 (1.06–2.23) ******** DysglycaemiaCFRDHba1c>48 1.08 (0.80–1.46)0.98 (0.62–1.58) NSNS Microbiology Pseudomonas aeruginosa Aspergillus Burkholderdia Cepacia Complex Staphylococcus aureus 0.69 (0.55–0.87)3.76 (2.93–4.82)0.59 (0.34–1.03) 1.46 (1.18–1.83) *****NS ** NS=notu2009statistically significant *=<0.05 **=<0.01 ***=<0.001 Conclusion Our data suggests CFRD is not an independent risk factor for SM growth in CF. The increased prevalence of SM in CFRD may be explained by increased intravenous antibiotic pressure in this group. Acknowledgement We would like to thank the CF Registry Research Committee for releasing the data used in this analysis.