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Introduction An outbreak of Influenza B occurred at a large United Kingdom (UK) regional adult cystic fibrosis (CF) centre in May 2016. This was late in the UK 2015–2016 influenza season and occurred on a specialist ward with strict infection control procedures. This study investigates the spread of influenza, clinical consequences and potential contributing factors. Methods Patient records, clinical status and pulmonary function data were reviewed for all inpatients during this period. Respiratory viral PCR results, influenza vaccination status of patients and staff, and environmental factors were also recorded. Affected patients were prospectively monitored for the following three months. Results 10 of 21 inpatients developed influenza B between 5th and 12th May 2016, an attack rate of 48%. All those characterised were confirmed as the same strain of influenza B/Victoria-lineage. Influenza infection resulted in a mean FEV1 reduction of 10.5% (SD 11.3, p = 0.012), which persisted at 3 months post infection (p = 0.003). Nine of the affected cases rooms were in close proximity on the ward while patients in the two isolation rooms with enhanced ventilation did not become infected. Ventilation measurements in affected rooms ranged from 1.75 to 2.10 air changes/hour, below national recommendations. Seventy percent of affected inpatients had received the 2015/16 trivalent seasonal influenza vaccine, which did not contain a B/Victoria-lineage influenza B virus. Conclusion This influenza B outbreak in CF adults had a high attack rate and a significant clinical impact. Room ventilation and a limited protection from the seasonal influenza vaccine were possible contributory factors.

BACKGROUND: Several treatment approaches in cystic fibrosis (CF) aim to correct CF transmembrane conductance regulator (CFTR) function; the efficacy of each approach is dependent on the mutation(s) present. A need remains for more effective treatments to correct functional deficits caused by the F508del mutation. METHODS: Two placebo-controlled, phase 2a studies evaluated GLPG2222, given orally once daily for 29 days, in subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS). The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms. RESULTS: Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6 mmol/L [GLPG2222 200 mg], p

Objectives: The COVID-19 pandemic has led to immense challenges for healthcare systems worldwide. People with cystic fibrosis (CF) were included in the clinically extremely vulnerable group for complications of coronavirus by the UK government and advised to shield during a national lockdown. Data suggests that pandemic-related restrictions have been linked to a reduction in pulmonary exacerbation events (PEx). We sought to explore whether an increase in medicine possession ratio and potentially adherence may be a factor in this finding. Methods: 50 patients who received medication through a homecare delivery system at a single large adult centre were randomly selected. Data from 12 months ‘pre-lockdown’ was compared to data for 9 months following start of shielding in March 2020. MPR was calculated and capped at 100%. Medications that were started or stopped during the pandemic were not included. Wilcoxon signed rank test was used to compare pre- and post-values. Results: 91 prescription medications were valid for analysis (45 nebulised antibiotics, 34 mucolytics and 12 CFTR modulators). MPR increased for 41 prescriptions (45.1%), decreased for 21 medications (23.1%) and remained unchanged for 29 medications (31.9%). Median MPR increased from 83% [57–100%] to 89% [66–100%], p = 0.037. MPR for nebulised antibiotics significantly increased (median 75% [54–100%] vs 89% [61–100%], p = 0.027). Median MPR for CFTR modulators was 100% throughout and did not change for mucolytics (75% [42–100%] vs 78% [53–100%], p = 0.419). Conclusion: We report a significant change in medication possession in adults with CF during the coronavirus pandemic in the UK. It is unclear whether this change translated to an increase in adherence but may be one factor in the reported decrease in PEx events described during this time. It is notable that increases were largely driven by inhaled antibiotics and this may represent a concerted effort to achieve maximal protection from infection.

a Genomic Diagnostics Laboratory, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK b Manchester Adult Cystic Fibrosis Centre, University Hospital of South Manchester, Southmoor Road, Manchester, M23 9LT, UK c Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester M23 9LT, UK

Introduction Since the discovery of the CF gene, over 1900 mutations have been described. The development of targeted CFTR-modulator therapy has made accurate recording of genotypes essential. In adult services, information regarding patients' genotypes is often inherited from paediatric services. Additionally, changes in the nomenclature of mutations has complicated recording of this information. These factors raise the potential for errors. Methods In the UK, clinicians input genetic information for CF patients into a national registry. We conducted a cross-sectional audit comparing data stored in the national registry to genotype results from the regional genomic laboratory for one large adult centre. Results 370 patients were registered in the national database. Information was available in 283 cases from the genetic laboratory. Results were concordant in 266 patients and discordant in 17, a 6% error rate. 8 of these errors were simple transcriptional errors. On 3 occasions microsatellite markers or polymorphisms were misinterpreted as mutations. In 4 cases the recorded genotype was incorrect, resulting in a mutation class shift for 2 patients. One patient with G551D [p.(Gly551Asp)] was entered as F508del [p.(Phe508del)], though clinicians were aware of this error prior to licensing of ivacaftor. In 2 cases the database was not updated with extended screening results. Conclusions Accurate genetic information is essential for access to appropriate medication, participation in clinical trials and prognosis. We highlight the potential for errors in recording this information in registries and databases. Centres should ensure processes are in place to prevent these errors.

Objectives Ivacaftor has led to significant benefits for patients with CF carrying the G551D mutation. The multisystem effects of CFTR modulation is increasingly recognised but often in the form of case reports. CF related diabetes has a significant impact on pulmonary function and mortality. We aimed to prospectively assess the effects of ivacaftor on glycaemic health. Methods We conducted a prospective observational study of patients with the G551D mutation. Baseline measures were recorded including spirometric measures, weight and sweat chloride. Glycaemic control was assessed using HbA1c and repeated measures were recorded at 1, 3, 6 and 12 months. Results Of 24 subjects included, 16 had normal glucose handling as defined by oral glucose tolerance test, 5 subjects had a diagnosis of CF-related diabetes and 3 subjects had impaired glucose tolerance prior to ivacaftor. FEV 1 , BMI and sweat chloride significantly improved at all timepoints compared to baseline. For the whole population, there was a significant decrease in HbA1c from baseline to 6 months: median 42.5 mmol/L vs 39.5 mmol/L, p=0.004. In patients with normal glucose tolerance there was a significant reduction in HbA1c at 3 (–2.1 mmol/L, p=0.027), 6 (–2.4 mmol/L, p=0.002) and 12 months (–1.9 mmol/L, p=0.03) compared to baseline. There were no significant changes in HbA1c or insulin requirements in the other subgroups. Conclusion Effective CFTR modulation may have an impact on the glycaemic health of patients with residual pancreatic endocrine function. These findings need to be followed longitudinally to see whether intervention with modulation therapy may protect against the development of CF related diabetes.

Objectives Ivacaftor has increased lung function and decreased pulmonary exacerbations and intravenous antibiotic use in patients with CF carrying the G551D mutation. This case study describes the effects of ivacaftor on airway microbiology and lung function in a G551D homozygote with chronic Pseudomonas aeruginosa (PA) infection. Methods All sputum culture reports prior to ivacaftor therapy were reviewed. Following ivacaftor initiation sputum samples were sent for standard culture at each clinic visit. 16S gene rRNA pyrosequencing was performed on paired sputum samples collected immediately prior to and after 6 months of ivacaftor therapy. FEV 1 was measured at baseline and at each follow up visit. Sweat chloride was assessed pre-treatment and at 6 months. Results Mucoid PA infection was acquired in 1983. The pre-ivacaftor baseline sputum sample and all preceding 26 samples taken over 8 years were culture positive for PA. 7 consecutive samples collected over 16 months following ivacaftor were culture negative for PA. A later sample was culture positive for the original infecting strain of PA (using variable number tandem repeat profiling). 16S gene rRNA pyrosequencing showed a drop in relative abundance of PA from 98.2% to 4.8% and an increase in microbial diversity over the 6 month sample period. FEV 1 improved from 68% predicted (baseline) to 90% predicted (20 months post ivacaftor). Sweat chloride reduced from 105 mmol/L (baseline) to 52 mmol/L (6months). Conclusion Bacterial diversity and relative abundance of typical CF pathogens may be significantly altered by modulation of both CFTR alleles. Sputum culture clearance of mucoid PA on should be interpreted with caution.

Background and Objectives: Fungi, particularly Aspergillus and Candida species, are increasingly found in cystic fibrosis (CF) airway fluids. However, their association with other CF pathogens, medications and lung function, especially in CF children, remains elusive. We analyzed the relationship of fungal colonization to microbiological and clinical parameters of pediatric CF patients. Methods and Results: Fungal colonization and long-term clinical parameters like BMI and lung function were retrospectively studied in over 500 CF patients. Colonization was defined based on Chotirmall et al. (Chest 2010). Candida albicans (CA) was the most prevalent fungus detected in CF airway fluids, followed by C. non-albicans > Aspergillus fumigatus (AF) > A. non-fumigatus species. We found an association between fungal colonization and (among other parameters) bacterial co-colonization, lung function, BMI and antibiotic therapy. Conclusion: This study suggests that colonization with CA or AF is affected by bacterial co-colonization and may modulate the disease severity already in pediatric CF patients.

E. Kerem1, M. Wilschanski1, I. Sermet-Gaudelus2, K. De Boeck3, F.J. Accurso4, M. Konstan5, S. Rowe6, N. Miller7, G. Elfring7, R. Spiegel7, S. Peltz7, J. Barth7, T. Ajayi7, Ataluren CF Study Group. 1Hadassah University Hospital, Jerusalem, Israel; 2Hopital Necker, Paris, France; 3University Hospital Leuven, Leuven, Belgium; 4Children’s Hospital Colorado, Aurora, United States; 5Rainbow Babies and Children’s Hospital, Cleveland, United States; 6University of Alabama-Birmingham, Birmingham, United States; 7PTC Therapeutics, Inc, South Plainfield, United States