N.J. Ronan

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor

Background Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Methods Thirty‐three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra‐low‐dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Results Significant improvements in FEV1, BMI, and sweat chloride levels were observed post‐ivacaftor treatment. Improvement in ultra‐low‐dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)‐1&bgr;, IL‐6, and IL‐8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Conclusions Early and sustained improvements on ultra‐low‐dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.

Current and emerging comorbidities in cystic fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed ubiquitously throughout the body. Thus, while respiratory manifestations dominate much of cystic fibrosis (CF) care, there are prominent multi-organ manifestations and comorbidities. In the general population, the number of comorbidities increases with aging. Few illnesses have experienced such a dramatic improvement in survival as CF, which has been transformed from an illness of childhood death to one of adult survival. Hence, as longevity increases in CF, it is paralleled by an increasing number of patients with multicomplex comorbidities availing of care from adult CF multi-disciplinary teams. This review gives an overview of the traditional CF associated comorbidities and those emerging in an aging adult cohort. While historically the treatment of CF focused on the consequences of CFTR dysfunction, the recent advent of CFTR modulators with the potential to enhance CFTR function represents an opportunity to potentially reverse or delay the development of some of the comorbidities associated with CF. Where evidence is available for the impact of CFTR modulatory therapy, namely ivacaftor on comorbidities in CF, this is highlighted.

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

BACKGROUNDnWe have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.nnnMETHODSnIn this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6u202fmonths after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).nnnRESULTSnAfter 1u202fmonth of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6u202fmonths. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (ru202f=u202f-0.5376; Pu202f<u202f.001 and ru202f=u202f-0.3285; Pu202f<u202f.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (βu202f=u202f-0.57, Pu202f=u202f.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581-0.863]; Pu202f=u202f.029) were used as classifier, especially in the first 2u202fmonths of treatment (0.806 [95% CI 0.665-0.947]; Pu202f<u202f.001).nnnCONCLUSIONSnThis study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.

217 Medical outcomes post transition of clinical care from a paediatric cystic fibrosis care model to an adult cystic fibrosis care model – an Irish perspective

As life-expectancy increases in CF it is paralleled by an increasing number of patients transitioning from a paediatric care-model to an adult care-model. In chronic illnesses’ including CF the transition process is often complicated by concerns about the potential implications. Traditionally studies have evaluated subjective aspects of transition including patient satisfaction. There are limited objective studies in this area. Our study investigated the change in clinical status in the year pre & post transition.