Regional Cystic Fibrosis Centre Research Articles

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study.

The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

Cystic Fibrosis in Adults: A Paradigm of Frailty Syndrome? An Observational Study.

This study aimed to assess the main clinical and anamnestic characteristics of adult Cystic Fibrosis (CF) patients and to evaluate the association of frailty with the CF genotyping classification. In an observational cross-sectional study, all ambulatory CF patients over 18 years old who received a diagnosis at the Regional Cystic Fibrosis Center for adults were enrolled and assessed by spirometry for respiratory function, by ADL and IADL for functional status, and by the Study of Osteoporotic Fractures (SOF) Index for frailty. The study population consisted of 139 CF patients (mean age 32.89 ± 10.94 years old, 46% women). Most of the subjects were robust (60.4%). The pre-frail/frail group was more frequently females (p = 0.020), had a lower BMI (p = 0.001), worse respiratory function, a higher number of pulmonary exacerbations/years, cycles of antibiotic therapy, and hospitalization (all p < 0.001) with respect to robust patients. The pre-frail/frail subjects used more drugs and were affected by more CF-related diseases (all p < 0.001). In relation to logistic regression, the best predictor of the pre-frail/frail status was a low FEV1 level. The CF patients show similarities to older pre-frail/frail subjects, suggesting that CF might be considered an early expression of this geriatric syndrome. This finding could help to better define the possible progression of CF, but overall, it could also suggest the usefulness employing of some tools used in the management and therapy of frailty subjects to identify the more severe CF subjects.

EPS9.05 Vantobra®, a new formulation of nebulised tobramycin: early real-world experiences at our large regional UK adult cystic fibrosis centre

EPS9.05 Vantobra®, a new formulation of nebulised tobramycin: early real-world experiences at our large regional UK adult cystic fibrosis centre

Isolation of Exophiala dermatitidis is not associated with worse clinical outcomes during acute pulmonary exacerbations in cystic fibrosis.

Introduction. The black yeast Exophiala dermatitidis has been isolated in respiratory samples from people with cystic fibrosis (CF). However, adequate detection may require longer incubation periods than the current UK national standard for CF respiratory samples. Furthermore, it is unclear whether isolation of E. dermatitidis is associated with poorer clinical outcomes in CF.Hypothesis/gap statement. E. dermatitidis does not cause clinically significant lung disease in CF adults.Aim. To evaluate differences in clinical outcomes over a 12 month period and during acute pulmonary exacerbations between CF adults with and without untreated E. dermatitidis.Methodology. Incubation times for respiratory samples on Sabouraud dextrose agar with chloramphenicol (SABC) plates at a large regional adult CF centre were extended from 2 to 7 days over a 1 month period. The number of patients from whom E. dermatitidis was isolated, and the length of incubation time prior to isolation, were recorded. Outcomes of treatment of exacerbations with intravenous antibiotics but in the absence of concomitant antifungal therapy were compared between those with and without E. dermatitidis, as were changes in lung function and body mass index (BMI) over a 12 month period.Results. Extended incubation unmasked the presence of E. dermatitidis in 22 of 132 patients; all isolations occurred after >48 h of incubation. Patients who isolated E. dermatitidis had lower rates of Pseudomonas aeruginosa isolation (P=0.02) and higher rates of non-tuberculous mycobacteria isolation (P=0.03), and were more likely to be prescribed a long-term antifungal medication (P=0.03), but had no differences in age, sex, baseline lung function or body mass index (BMI). There were no differences in response to treatment of acute exacerbations between patients with and without E. dermatitidis, or in change in forced expiratory volume in 1 s (FEV1), BMI and number of exacerbations over 12 months of follow-up.Conclusion. E. dermatitidis is not associated with worse clinical outcomes in CF. Given potential side effects and drug interactions, routine targeting of E. dermatitidis with antifungals during acute exacerbations is not advised.

A prospective randomised controlled mixed-methods pilot study of home monitoring in adults with cystic fibrosis.

Background:Home monitoring (HM) is able to detect more pulmonary exacerbations (PEx) than routine care (RC) in individuals with cystic fibrosis (CF), but there is currently no evidence for benefits in health outcomes. Patient experiences of using HM and a health economics assessment have not been rigorously assessed to date. This study aimed to assess the effects of HM on hospital admissions, quality of life, antibiotic requirements, exacerbation frequency, lung function, nutritional outcomes, anxiety, depression, costs and health outcomes, as well as the qualitative effects on the patient experience.Methods:This randomised controlled mixed-methods pilot study recruited CF adults cared for in one large regional CF centre. Participants were randomly allocated 1:1 to the intervention cohort [twice-weekly HM of symptoms measured by the Cystic Fibrosis Respiratory Symptom Diary – Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) and forced expiratory volume in one second (FEV1)] or a control cohort (routine clinical care) for the 12-month study period. Measurements were recorded at study visits at baseline, 3, 6, 9 and 12 months. Spirometry, body weight, comorbidities, medications, hospital inpatient days, courses of antibiotics (oral and intravenous) and PEx (defined by the modified Fuchs criteria) were recorded at each study visit. Health status, capability and cost-effectiveness were measured at each study visit by the Hospital Anxiety and Depression Scale (HADS), the ICEpop CAPability measure for Adults (ICECAP-A), EuroQol 5 dimensions (EQ-5D-5L) questionnaire and an adapted resource use questionnaire. The patient experience of HM was assessed by semi-structured qualitative interviews at baseline and 12 months.Results:Eighty-eight participants were recruited, with 44 (50%) randomised to receive HM and 44 (50%) randomised to receive RC. Patient hospital inpatient bed days per annum and overall health-related quality of life were similar between the groups. Protocol-defined PEx requiring intravenous and oral antibiotics were detected more frequently in the HM group, with no other differences between the groups in the secondary outcomes. The total mean National Health Service (NHS) costs were approximately £1500 more per patient for the RC arm than the HM group. The qualitative analysis demonstrated that the patient experience of HM was generally positive and overall the intervention was well accepted.Conclusion:The findings of this trial confirm that HM is effective in detecting PEx in adults with CF. There were no significant differences in hospital inpatient bed days and overall health-related quality of life between the groups. Despite the cost of the HM equipment and the salary of the research fellow to respond to the results, health economics analysis suggests the intervention was less expensive than RC. HM was generally well accepted, with most participants reporting that it resulted in them feeling more empowered and reassured.Trial registrationThe study protocol was registered with Clinicaltrials.gov (NCT02994706) on 16 July 2014 and published in a peer reviewed journal.Data from this trial has been presented in abstract form at the ECFS Conference in Lyon in September 2020.

Handgrip Strength and Pulmonary Function in the Pediatric Cystic Fibrosis Population

Identify indicators of nutrition status that predict pulmonary function within pediatric cystic fibrosis patients. In Cystic Fibrosis (CF), adequate nutrition promotes good pulmonary function and overall quality of life. Handgrip strength (HGS) has promise as an indicator for nutrition status and predictor of pulmonary function, with associations found in adult CF. The purpose of this study is to determine, in pediatric CF, if HGS is associated with pulmonary function, and if it is a better predictor compared to body mass index (BMI), the current nutrition measurement. This is a cross-sectional, retrospective chart review of 48 pediatric patients followed at the Nebraska Regional Cystic Fibrosis Center, Pediatric Program. Associations between HGS, BMI, and pulmonary function measures (FEV1, FVC) were assessed using linear regression and adjusted for age and sex. Significant associations were found between HGS and percent predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) (β=1.347, p = 0.001 and β=1.278, p < 0.001, respectively). BMI was also significantly associated with percent predicted FEV1 and FVC (β=2.380, p = 0.033 and β=2.151, p = 0.027, respectively). HGS was found to have a significant association to pulmonary function, however BMI remains a strong predictor. These results support the continued use of BMI as a primary measurement for nutrition status in the CF population. HGS is a promising tool for clinic use and more research is needed to evaluate its efficacy within the pediatric CF population.

P231 Patient experience of accessing a virtual cystic fibrosis service during the 2020 SARS-CoV-2 pandemic in Blackpool, North West of England

In 2015 Regional Specialist Commissioners awarded Blackpool Teaching Hospitals the commission of a new regional cystic fibrosis centre in the North West of England. The Blackpool Adult Cystic Fibrosis Service (BACFS) opened in February 2017 and was the first entirely new UK adult CF centre in three decades. Objective: To explore patient experiences of accessing a virtual adult cystic fibrosis service during the SARS-CoV-2 pandemic, to inform future practice and service development. Method: Between December 2020 and January 2021, 44 patients, accessing a blended approach to care through both virtual and face-to-face appointments, where necessary, were offered a CF-related adaptation of our hospital's Friends and Family Test. The questionnaire provided the mechanism to explore patient satisfaction and experience of BACFS during the pandemic (March 2020–December 2020) giving opportunity to critically appraise the service and their virtual experience. Results: Response rate was 18%. 100% of patients rated the service as either good or excellent, demonstrating care and compassion, being listened to, developing autonomy over their healthcare with shared action plans and improving confidence in the management of their condition. 50% of patients reported their virtual experience was ‘very good’ and 50% ‘good’, with 100% of patients reporting the frequency of their appointments was ‘just right’. Further qualitative themes of the virtual experience are presented, including convenience of appointments and feeling connected with the team during the pandemic. Conclusion: The data presented demonstrates that patients value the service provided by BACFS. Patients have been supportive of the virtual service provision with a suggestion that the offering may continue as we consider service delivery post SARS-CoV-2. The adapted patient experience questionnaire continues to drive service development and inform our approaches in alternative ways to engage our patients.

Diffusion and Characterization of Pseudomonas aeruginosa Aminoglycoside Resistance in an Italian Regional Cystic Fibrosis Centre.

Extensively-drug-resistant Pseudomonas aeruginosa constitutes a serious threat to patients suffering from Cystic Fibrosis (CF). In these patients, P. aeruginosa lung infection is commonly treated with aminoglycosides, but treatments are largely unsuccessful due a variety of resistance mechanisms. Here we investigate the prevalence of resistance to gentamicin, amikacin and tobramycin and the main aminoglycoside resistance genes found in P. aeruginosa strains isolated at a regional CF centre. A total number of 147 randomly selected P. aeruginosa strains isolated from respiratory samples sent by the Marche regional Cystic Fibrosis Centre to the Microbiology lab, were included in this study. Of these, 78 (53%) were resistant to at least one of the three aminoglycosides tested and 27% were resistant to all three antibiotics, suggesting a major involvement of a chromosome-encoded mechanism, likely MexXY-OprM efflux pump overexpression. A specific pathogenic clone (found in 7/78 of the aminoglycoside resistant strains) carrying ant(2″)-Ia was isolated over time from the same patient, suggesting a role for this additional resistance gene in the antibiotic unresponsiveness of CF patients. The MexXY-OprM efflux pump is confirmed as the resistance determinant involved most frequently in P. aeruginosa aminoglycoside resistance of CF lung infections, followed by the ant(2″)-Ia-encoded adenylyltransferase. The latter may prove to be a novel target for new antimicrobial combinations against P. aeruginosa.

WS11-4 Current clinical practice in the management of cystic fibrosis-related bone disease in a regional UK adult cystic fibrosis centre

WS11-4 Current clinical practice in the management of cystic fibrosis-related bone disease in a regional UK adult cystic fibrosis centre

Persistent Adherence to Airway Clearance Therapy in Adults With Cystic Fibrosis.

Airway clearance therapy (ACT) is a core component of daily treatment for cystic fibrosis (CF). However, surprisingly little is known about sustained or persistent use of ACT over time among adults with CF. This longitudinal study examined persistent adherence to ACT over 12 months and its modifiable predictors, drawing on aspects of Social Cognitive Theory and the Theory of Planned Behavior. Subjects were drawn from a regional CF center in the southern United States. Predictor variables evaluated at baseline included self-efficacy for ACT (ie, self-confidence in overcoming barriers), outcome expectations (ie, perceived necessity of ACT and concerns about its disruptive effects), and subjective norms (ie, perceptions of being influenced by others). The Cystic Fibrosis Treatment Questionnaire (CFTQ) was used to assess self-reported adherence to ACT at baseline, at 6 months, and at 12 months. The mean age of subjects was 27.2 ± 9.1 y, and mean FEV1% predicted was 65.5 ± 24.8. Forty-six percent of subjects reported persistent use of ACT (classified as adherent at all assessment periods). In bivariate analyses, all social cognitive predictor variables assessed at baseline were significantly related to persistent adherence (all P < .03), except subjective norms. In logistic regression analyses that modeled the effects of these predictors simultaneously while controlling for FEV1%, fewer baseline concerns about ACT (odds ratio = 0.82, 95% CI 0.69-0.99) and greater self-efficacy (odds ratio = 1.09, 95% CI 1.01-1.18) remained significant independent predictors. This longitudinal study addresses an important gap in the literature regarding adherence to ACT over time (12 mo) in a routine clinical setting. Persistent adherence was problematic. As anticipated, social cognitive variables (self-confidence and perceived concerns) predicted self-reported persistence, and these may represent practical targets for intervention.

254 Feasibility of implementing cardiopulmonary exercise testing in a regional paediatric cystic fibrosis centre in the UK

254 Feasibility of implementing cardiopulmonary exercise testing in a regional paediatric cystic fibrosis centre in the UK

A prospective pilot study of home monitoring in adults with cystic fibrosis (HOME-CF): protocol for a randomised controlled trial

BackgroundHome monitoring has the potential to detect early pulmonary exacerbations in people with cystic fibrosis (CF), with consequent improvements in health outcomes and healthcare associated costs. This study aims to assess the effects of home monitoring on hospital admissions, quality of life, antibiotic requirements, exacerbation frequency, lung function, nutritional outcomes, anxiety, depression, costs and health outcomes, as well as the qualitative effects on the patient experience.MethodsThis randomised controlled mixed-methods trial aims to recruit 100 adults with CF cared for in one large regional CF centre. Participants are randomly allocated 1:1 to the intervention group (twice-weekly home monitoring of symptoms measured by the Cystic Fibrosis Respiratory Symptom Diary – Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) and Forced Expiratory Volume in one second (FEV1)) or a control group (routine clinical care) for the 12-month study period. Measurements are recorded at study visits at baseline, 3, 6, 9 and 12 months. Spirometry, body weight, co-morbidities, medications, hospital inpatient days, courses of antibiotics (oral and intravenous), pulmonary exacerbations (defined by the modified Fuchs criteria) are recorded at each study visit. Health status, capability and health economics are measured at each study visit by the Hospital Anxiety and Depression Scale (HADS), the ICEpop CAPability measure for Adults (ICECAP-A), EuroQol 5 dimensions (EQ-5D-5L) questionnaire and an adapted resource use questionnaire. The patient experience is assessed by semi-structured qualitative interviews at baseline and 12 months.DiscussionResults from this study will help to determine the effect of home monitoring on inpatient bed days and quality of life in adults with CF, as well as other relevant health and health economic outcomes.Trial registrationThis study protocol is registered with Clinicaltrials.gov (NCT02994706), date registered 16th July 2014

205 Folate deficiency in adult patients at a regional cystic fibrosis (CF) centre

205 Folate deficiency in adult patients at a regional cystic fibrosis (CF) centre

Paranasal sinus pathogens in children with cystic fibrosis: Do they relate to lower respiratory tract pathogens and is eradication successful?

BackgroundThe study aims were to assess the association of microflora between the paranasal sinus and the lower airways of children attending a regional paediatric cystic fibrosis centre and to determine the performance of an eradication treatment protocol for positive paranasal sinus samples. MethodPaired nasal lavage and lower airway samples (cough swabs or sputum) were taken from 54 children with cystic fibrosis (median age 11years). Positive paranasal sinus samples received eradication treatment, using oral and sinonasal nebulised antibiotics. ResultsA correlation between paranasal sinus and lower airways was detected in 33/54 paired timed samples (p<0.02). Of 4/54 children who reported sinus symptoms, only 2 had paranasal sinus positive samples. 28 positive nasal lavage samples cultured 8 Pseudomonas aeruginosa (PA), 8 Staphylococcus aureus (SA) and 12 other bacterial pathogens. Eradication using sinonasal nebulised antibiotics and oral antibiotics showed a success of 14/21 (67%) treated paranasal sinus positive samples at 1month & 3months after treatment. Success rate was 75% in the PA group and 71% in the SA group. Ongoing monitoring with nasal lavage will continue. ConclusionThere was agreement between pathogens or lack of them found in the paranasal sinus and lower airways. Paranasal infection is often asymptomatic in children with cystic fibrosis. The eradication protocol for paranasal sinus pathogens had a good success rate.

107 Bronchial infection with Burkholderia cepacia complex in cystic fibrosis. Experience at a Spanish regional cystic fibrosis centre

107 Bronchial infection with Burkholderia cepacia complex in cystic fibrosis. Experience at a Spanish regional cystic fibrosis centre

289 Vitamin D deficiency in patients attending the Tuscan regional cystic fibrosis centre

289 Vitamin D deficiency in patients attending the Tuscan regional cystic fibrosis centre

Adherence to nebulised therapies in adolescents with cystic fibrosis is best on week-days during school term-time

Treatment regimen for families of children with cystic fibrosis (CF) is considerable, particularly when nebulised therapies for chronic Pseudomonas aeruginosa airway infection are prescribed. Adherence to these regimens is variable, particularly in adolescence. Previously, we reported children to be more adherent in evenings compared to mornings, suggesting an association with time-pressure. The aim of this study was to determine whether adherence would be better in adolescent patients at weekends and during school holidays when time-pressures may be less. 24 patients (14 male, median [range] age 13.9 [11.1-16.8] years) were enrolled from two regional paediatric CF centres in the United Kingdom. Data for a full scholastic year, were downloaded openly from a breath-activated data logging nebuliser (I-neb™). Adherence (% of doses taken÷expected number) was calculated during term-times, holidays, weekends and weekdays, for each patient. Large variations in adherence were seen between patients. However, adherence during term-time was significantly better than holidays (p<0.001). Weekday adherence was better than weekend adherence in term-time but not holidays. Interestingly, patients prescribed three daily treatments took on average 1.4 treatments/day, a similar number to those prescribed two daily treatments. Overall adherence to inhaled therapies was reasonable, but significantly reduced during holiday periods. This suggests a need for families to have not only time, but also structure in their daily routine to maintain optimal adherence to long-term therapies. It is important for CF teams to appreciate these factors when supporting families.

Microbial contamination of non-invasive ventilation devices used by adults with cystic fibrosis

There is currently little evidence regarding potential risks of bacterial contamination of non-invasive ventilation (NIV) devices used by cystic fibrosis (CF) patients. The aim of this study was to determine the extent of bacterial contamination of NIV devices in our regional adult CF centre. Seven NIV devices recently used by CF patients chronically infected with Pseudomonasaeruginosa or Burkholderiacepacia complex (BCC) were swabbed in seven areas, both external and internal. Two devices had undergone ethylene oxide (EtO) sterilization between patient use and swabbing, and five devices had not undergone EtO sterilization. Swabs from five devices had insignificant growth of environmental organisms and two devices had significant growth of environmental organisms. No CF pathogens were isolated from any machine. No evidence was found of pathogenic microbial contamination of NIV devices used by CF patients in this small study. We suggest that further studies examine for evidence of bacterial contamination of NIV devices and that this issue should be included in future CF infection control guidelines.

Bloodstream infections in cystic fibrosis: Nine years of experience in both adults and children

BackgroundWe report the aetiology and outcome of bloodstream infections (BSI) occurring at two regional cystic fibrosis (CF) centres (one adult, one paediatric) between 1998 and 2006. MethodsA retrospective analysis of all positive blood cultures during the study period was performed. ResultsDuring the study period 1691 blood culture sets were taken. Fifty-seven clinically significant episodes of BSI in 48 people with CF (36 adult, 12 paediatric) were identified, along with 28 other episodes considered to be contamination or not clinically significant. The most common BSIs were caused by coagulase-negative staphylococci (13) Candida spp (10), and Stenotrophomonas maltophilia (8). The majority (82%) of significant BSIs were considered to originate from totally-implantable vascular access devices (TIVADs); only 9% were attributed to the lower respiratory tract. The TIVAD was removed in two-thirds of cases of TIVAD-associated BSI. There were three deaths (60% of cases) attributable to BSI originating from the lower respiratory tract but no deaths attributable to TIVAD-associated BSI. ConclusionMost significant BSIs in patients with CF originate from TIVADs. Targeted antimicrobial therapy and appropriate early device removal is associated with good clinical outcome. BSI originating from the lower respiratory tract is associated with poor clinical outcome.

Prevalence and possible sources of Achromobacter хylosoxidans and Stenotraphomonas maltophilia infection at a cystic fibrosis center

Summary. Achromobacter хylosoxidans and Stenotraphomonas maltophilia become increasingly important pathogens of lung disease in cystic fibrosis (CF) patients. Little is known about clinical significance and routes of transmission of these pathogens from environmental or hospital sources to the patient. The aim of this study was to assess a prevalence of A. хylosoxidans and S. maltophilia in a regional population of CF patients and possible hospital sources of this infection. Microbiological investigation was performed in 259 sputum samples and nasopharyngeal aspirates from 38 CF patients attending the Regional Cystic Fibrosis Center in 2010. Bacterial isolates were obtained from hospital environment (sinks in wards and toilets, physiotherapeutic equipment, nebulizers) and from hands of medical care providers (n = 50). Four (10.5 %) of patients were colonised by A. хylosoxidans. In six patients (15.8 %) S. maltophilia was detected. In 8 cases (80 %) bacterial pathogens were detected in sputum samples of the patients after i.v. or nebulised anti-pseudomonal therapy and hospitalisations. A. хylosoxidans and S. maltophilia were also isolated from sinks at common infection wards (33.2 % and 66.7 %, respectively); 40 % of toilets were contaminated with A. хylosoxidans and S. maltophilia strains. One S. maltophilia strain was isolated from high frequency chest wall oscillation vest and one S. maltophilia strain was isolated from the hands of a physiotherapist at the end of a working day. Similarity of antibiotic susceptibility of the strains isolated from the hospital equipment and from the patients suggested a possible trasmission of the infection from the hospital environment and hands of medical care providers to the patients. Therefore, a role of A. хylosoxidans and S. maltophilia for respiratory disease in CF patients could be underestimated. Improved hygienic measures in CF centers are required to prevent risk of bacterial transmission.