CF Adults Research Articles

P376 The occurrence of side effects after administration of ETI in Czech CF adults

P376 The occurrence of side effects after administration of ETI in Czech CF adults

A longitudinal analysis of respiratory symptoms in people with cystic fibrosis with advanced lung disease on and off ETI

People with CF (PwCF), particularly those with advanced lung disease (ALD), experience frequent respiratory symptoms. A major CF breakthrough was the approval of elexacaftor/tezacaftor/ivacaftor (ETI) in 2019, which has been shown to improve symptoms and lung function in the CF population, and decrease pulmonary exacerbations. The purpose of this study was to analyze longitudinal changes in respiratory symptoms over 24 months in ETI-treated and untreated PwCF with ALD Symptoms were measured among CF adults with ppFEV1 < 40% (N = 48, 24 ETI-treated, 24 untreated) using the CFRSD-CRISS and the CFQ-R [respiratory]. Two multilevel growth models assessed the rate of change in symptoms overall and within the ETI-treated and untreated groups. PwCF on ETI had significantly lower symptom severity over 24 months than those not on ETI as measured by the CRISS and CFQ-R. The ETI-treated group maintained an -11.7 and +19.3 point difference(p<0.01) in CRISS and CFQ-R scores over the study compared to the non-ETI group, achieving minimal clinically important differences on average between groups on both instruments. No change in the symptom burden trajectory between groups was observed (p = 0.58). Even with ALD, ETI-treated PwCF have a lower respiratory burden than those not on ETI. This may be confounded by survivorship bias in the non-ETI group. Of note, in this ALD cohort, neither instrument demonstrated ceiling effects. Our results suggest that, while ETI has significantly improved the lived experience, PwCF with ALD are still plagued by respiratory symptoms.

The determinants of survival among adults with cystic fibrosis\u2014a cohort study

BackgroundCystic fibrosis (CF) is one of the most common autosomal recessive diseases. Factors contributing to disease exacerbations and survival rate of CF patients are type of mutation in the CFTR gene, poor nutritional status, lung failure, and infection development by Pseudomonas aeruginosa. The study aimed to evaluate the relationship between the severity of mutation, nutritional status, lung function, and Pseudomonas aeruginosa prevalence and survival rate in adult patients with cystic fibrosis.MethodsA study of 124 (68 ♀ and 56 ♂) adults with CF aged 18–51 years were evaluated for (a) type of mutation in the CFTR gene, (b) nutritional status (BMI), (c) lung function (FEV1%), and (d) Pseudomonas aeruginosa prevalence. For statistical calculations, Kaplan-Meier analysis of survival, chi-squared test for multiple samples, and logistic regression were used.ResultsThe type of mutation (χ2 = 12.73, df = 3, p = 0.005), FEV1% (χ2 = 15.20, df = 2, p = 0.0005), Pseudomonas aeruginosa prevalence (χ2 = 11.48, df = 3, p = 0.009), and BMI (χ2 = 31.08, df = 4, p < 0.000) significantly differentiated the probability of survival of patients with CF. The shortest life expectancy was observed in patients with a severe type of mutation on both alleles, FEV1% < 40, subjects in whom Pseudomonas culture was extensively drug-resistant or pandrug-resistant, and patients whose BMI was lower than 18.5 kg/m2. The period from 30 to 40 years of age was the most critical in CF adults’ lifespan. The risk of adults with CF death doubled with Pseudomonas aeruginosa prevalence (OR = 2.06, 95% CI 1.29; 2.28) and eightfold when the bacteria acquired antibiotic resistance (OR = 8.11, 95% CI 1.67; 38.15).ConclusionsAll factors included in the study were significantly related to the survival rate of patients with cystic fibrosis.

Developing a Decision Aid to Facilitate Informed Decision Making About Invasive Mechanical Ventilation and Lung Transplantation Among Adults With Cystic Fibrosis: Usability Testing.

BackgroundCystic fibrosis (CF) is a life-limiting genetic disease that causes chronic lung infections. We developed an internet-based decision aid (DA) to help patients with CF make better informed decisions regarding treatments and advance care planning. We built the DA around two major treatment decisions: whether to have a lung transplant and whether to agree to invasive mechanical ventilation (intubation).ObjectiveThis study aims to conduct usability testing of the InformedChoices CF DA among key stakeholder groups.MethodsWe performed a patient needs assessment using think-aloud usability testing with patients with CF, their surrogates, and CF clinicians. Think-aloud participants provided feedback while navigating the DA, and after viewing, they answered surveys. Transcripts from the think-aloud sessions and survey results were categorized into common, generalizable themes and optimizations for improving content, comprehension, and navigation. We assessed the ease of use of the DA (System Usability Scale) and also assessed the participants’ perceptions regarding the overall tone, with an emphasis on emotional reactions to the DA content, level of detail, and usefulness of the information for making decisions about either intubation or lung transplantation, including how well they understood the information and were able to apply it to their own decision-making process. We also assessed the DA’s ease of navigation, esthetics, and whether participants were able to complete a series of usability tasks (eg, locating specific information in the DA or using the interactive survival estimates calculator) to ensure that the website was easy to navigate during the clinic-based advance care planning discussions.ResultsA total of 12 participants from 3 sites were enrolled from March 9 to August 30, 2018, for the usability testing: 5 CF clinicians (mean age 48.2, SD 12.0 years), 5 adults with CF, and 2 family and surrogate caregivers of people with CF (mean age of CF adults and family and surrogate caregivers 38.8, SD 10.8 years). Among the 12 participants, the average System Usability Scale score for the DA was 88.33 (excellent). Think-aloud analysis identified 3 themes: functionality, visibility and navigation, and content and usefulness. Areas for improvement included reducing repetition, enhancing comprehension, and changing the flow. Several changes to improve the content and usefulness of the DA were recommended, including adding information about alternatives to childbearing, such as adoption and surrogacy. On the basis of survey responses, we found that the navigation of the site was easy for clinicians, patients, and surrogates who participated in usability testing.ConclusionsUsability testing revealed areas of potential improvement. Testing also yielded positive feedback, suggesting the DA’s future success. Integrating changes before implementation should improve the DA’s comprehension, navigation, and usefulness and lead to greater adoption.

IgA autoantibodies directed against self DNA are elevated in cystic fibrosis and associated with more severe lung dysfunction

Although extracellular host DNA (ecDNA) levels in CF airways were linked to airflow obstruction and recombinant DNAse therapy is beneficial for CF patients, it remains incompletely understood whether ecDNA also leads to an autoimmune response. Here we hypothesized that chronic presence of DNA in CF airways triggers the production of autoantibodies targeting host human DNA. We measured the levels of IgA autoantibodies recognising host double-stranded (ds) DNA in the blood and sputum samples of CF patients and only sera of controls subjects and patients suffering from rheumatoid arthritis and systemic lupus erythematosus (SLE) that served as non-CF, autoimmune disease cohorts. We found that concentrations of anti-dsDNA IgA, but not IgG, autoantibodies in the circulation were significantly elevated in adult CF patients compared to age-matched, control subjects. Systemic levels of anti-dsDNA IgA antibodies negatively correlated with FEV1% predicted, a measure of lung function, in CF patients. Anti-dsDNA IgA autoantibodies were also detected in CF sputa but sputum levels did not correlate with the degree of airway obstruction or sputum levels of DNA. We also found elevated autoantibody levels in CF children as 76.5% of CF patients younger than 10 years and 87.5% of CF patients 10–21 years had higher blood anti-dsDNA IgA levels than the highest value found in healthy control adults. Overall, our results detect elevated systemic anti-dsDNA IgA autoantibody levels in CF adults, teenagers and young children. We speculate that the appearance of an autoimmune response against host DNA in CF is an early event potentially contributing to disease pathogenesis. Highlights CF serum contains elevated levels of anti-dsDNA IgA, but not anti-dsDNA IgG, autoantibodies Anti-dsDNA IgA autoantibody levels in serum correlate with airflow obstruction in CF Anti-dsDNA IgA autoantibodies are detected in CF sputum but do not correlate with airflow obstruction Anti-dsDNA IgA autoantibodies are also elevated in the blood of the majority of CF toddlers and youth

A115 MODELING CYSTIC FIBROSIS (CF) INTESTINAL DISEASE USING PATIENT DERIVED TISSUES

Abstract Background Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes for a chloride/bicarbonate anion channel expressed on the apical membrane of most epithelial tissues, such as the lungs, liver, pancreas, small and large intestines, and reproductive tissues. CFTR is responsible for the transport of chloride and bicarbonate ions to maintain tissue surface hydration and pH balance of epithelial tissues. Historically, recurrent lung infections have been the most common cause of mortality in CF patients. With advances in clinical care and therapeutics, the current mean survival age of Canadian patients has increased to 52.3 years. However, this increase in survival has also been associated with an elevated risk of developing gastrointestinal cancers in CF adults. Compared to the general public, CF patients are 10 times more likely to develop cancer. This risk is increased to 25-20 times in patients that have undergone organ transplantations. Although the exact molecular mechanism regarding increased cancer risk in CF remains unclear, chronic intestinal inflammation has been known to contribute to elevated cancer development. Aims CF patients display an increased baseline inflammatory status that is exacerbated with microbiome exposure leading to possible increased risk for inflammation-mediated cancer development. Methods To reduce inter-patient heterogeneity, we have differentiated human intestinal organoids using induced pluripotent stem cells from homozygous F508del CF patients and gene edited isogenic non-CF (Wt-CFTR) controls. We conducted gene expression studies using RT-qPCR to determine baseline differences in gene expression prior to environmental exposures and following exposure to LPS and flagellin. Results We determined the expression levels of stem cell, intestinal epithelial cell, innate immunity genes and differentiation markers and found expression of such genes were not significantly different between 3D CF and gene-edited non-CF organoids. We are currently conducting RNA sequencing to survey expression pattern of all genes to definitively determine possible fundamental changes in the CF intestinal epithelium and determining the effect of LPS and flagellin treatment to determine if there is an altered response to inflammatory stimuli. Conclusions iPSC derived HIOs is a novel, patient based, and renewable model that can be used to dissect the primary intestinal pathologies in CF. Transcriptomic data of CF HIOs at steady state will provide insights to possible developmental defects. Complex interactions between the host intestinal epithelia and the commensal microbiome can also be investigated using this model. Funding Agencies CAG

Identification of novel blood biomarkers of treatment response in cystic fibrosis pulmonary exacerbations by label-free quantitative proteomics

Pulmonary exacerbations (PEx) are clinically impactful events for individuals with CF. Unfortunately, many CF individuals with PEx fail to regain their baseline lung function despite treatment. The objective of this study was to use unbiased proteomic technology to identify novel blood protein biomarkers that change following intravenous (IV) antibiotic treatment and to explore if changes correlate with clinical response by the end of treatment. Blood samples from 25 PEx events derived from 22 unique CF adults were collected within 24 hours of hospital admission, day 5, day 10, and IV antibiotic completion. Three-hundred and forty-six blood proteins were evaluated with label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative proteomics and immunoassays. Forty-seven plasma proteins changed significantly following 5 days of IV antibiotic treatment (q-value ≤ 0.10). Early change in IGF2R from hospital admission to day 5 correlated with overall change in symptom score (CFRSD-CRISS) by the end of treatment (r = −0.48, p-value = 0.04). Several plasma proteins identified and quantified by label-free LC-MS/MS changed early following treatment with IV antibiotics and many of these proteins are involved in complement activation and inflammatory/immune-related pathways. Early change in IGF2R correlated with symptom response following IV antibiotic treatment and requires further validation as a predictive biomarker of symptom response.

Cystic fibrosis related diabetes: Pathophysiology, screening and diagnosis

Cystic fibrosis related diabetes (CFRD) is a distinct form of diabetes that is associated with significantly increased morbidity and mortality in the CF population. The primary etiology is relative insulin insufficiency secondary to destruction of pancreatic islets, and to other factors that affect the function of the remaining beta cells. The prevalence of CFRD increases markedly with age and more than half of CF adults develop the disease. As the initial presentation of CFRD may be clinically silent, annual screening is recommended starting at least by the age of 10 with an oral glucose tolerance test (OGTT). The importance of an early diagnosis is based on the association of diabetes and abnormal glucose tolerance with worse health outcomes in patients with CF, and evidence that early treatment of diabetes improves prognosis. This review presents a concise overview of the current understanding of CFRD pathogenesis, natural history, screening and diagnosis.

Using qualitative methods to inform the design of a decision aid for people with advanced cystic fibrosis: The InformedChoices CF patient decision aid

ObjectiveTo assess information needs of adults with Cystic Fibrosis and their families toward designing a patient decision aid about invasive mechanical ventilation (IMV) and lung transplant. MethodsFocus groups and in-depth interviews explored participants’ knowledge, prior clinical conversations, and decisions about IMV and lung transplant. Interviews and focus groups were recorded and transcribed for analysis. ResultsN = 24 participants were recruited. Themes identified were: prior communication with clinicians, decision-making process, and living with CF. Participants having prior conversations with CF clinicians regarding: lung transplant (N = 17/74%), and IMV (N = 3/13%). Most 15(65%) felt it was important to hear patients’ real-life experience, others (3/13%) relied on their CF doctors for information. Most people (16/70%) believed hearing prognosis was helpful, but 5(22%) found this information frightening. High degrees of social isolation and a desire for more interaction with other CF adults were found. ConclusionsQualitative methods helped identify areas important for decision making about IMV and LT for CF adults. Future directions include usability and feasibility testing of the decision aid. Practice implicationsBecause IMV is rarely discussed with CF adults, clinicians might approach this topic, as with transplant, as lung function begins to decline. CF-care teams should also foster CF patient-level information exchange.

Blood biomarkers to predict short-term pulmonary exacerbation risk in children and adolescents with CF: A pilot study

In CF, pulmonary exacerbations (PEx) can lead to permanent loss in lung function and thus should be prevented. Previously, we identified a blood protein biosignature consisting of 6 proteins capable of predicting short-term PEx events in CF adults. In this study, we utilized blood samples from the placebo arm of a randomized controlled trial to assess whether this candidate protein biosignature was also capable of predicting short-term PEx events in CF children and adolescents. This pilot study provides preliminary evidence that blood inflammation can be monitored to predict short-term PEx risk in CF children and adolescents.

The evaluation of α-tocopherol concentration instead of α-tocopherol:cholesterol ratio in adult cystic fibrosis patients results in the overestimation of vitamin E deficiency

Introduction. It has been suggested that serum vitamin E concentrations in CF patients may not properly reflect the body resources of vitamin E. Therefore, we aimed to assess vitamin E status in CF adults relating it to reference values for healthy subjects, also taking into account the α‑tocopherol:cholesterol ratio. Material and Methods. The study group was composed of 33 CF patients − 18 (54.5%) females and 15 (45.5%) males − aged from 18 to 47 years. In all CF patients nutritional status and clinical expression of disease − lung function; Pseudomonas aeruginosa colonization; diabetes; cirrhosis; exocrine pancreatic function and vitamin E supplementation were analyzed. Vitamin E (α‑tocopherol) concentration was assessed by high‑performance liquid chromatography (HPLC).Resuls. CF adults have lower vitamin E concentrations (median: 830 µg/dl vs. 1132 µg/dl, p = 0.00174) and higher vitamin E: cholesterol ratio (median: 7.2 mg/g vs. 6.7 mg/g, p &lt; 0.00001) than healthy subjects. The underlying factor that determines this phenomenon is related to low cholesterol levels observed in CF patients. The percentage of low vitamin E concentrations defined in comparison to healthy Polish peers is considerably higher than low vitamin E:cholesterol ratios (39.4% vs. 21.2%, p = 0.0011). Conclusions. The evaluation of α‑tocopherol concentration instead of α‑tocopherol:cholesterol ratio in CF adults results in the overestimation of vitamin E deficiency. Moreover, there is also potentially a large percentage of individuals with excessive vitamin E body resources. However, this aspect demands further studies.

A survey identifying nutritional needs in a contemporary adult cystic fibrosis cohort

BackgroundCystic fibrosis (CF) is a disease in which nutritional barriers are diverse and common, with malnutrition greatly influencing pulmonary trajectory and overall outcomes. Despite this, the most effective methods to optimize CF nutrition are unknown, and literature describing patients’ perspectives on their specific nutritional needs is lacking, particularly in the modern era of CF care. This study aimed to identify the most important nutritional needs and desired health-improvement resources in a contemporary adult CF cohort.MethodsA 14-question investigator-designed survey addressing nutrition concerns, preferred health-improvement resources, and dietary/exercise routines was administered to CF adults. Clinical characteristics and survey responses are presented with descriptive statistics, and responses compared by body mass index (BMI) category (< 18.5 kg/m2; 18.5–24.99 kg/m2; 25–29.99 kg/m2; ≥30 kg/m2), gender, and socioeconomic status using Chi square or Fisher’s Exact testing.ResultsOf 66 total patients, nine (13.6%) were underweight (BMI < 18.5 kg/m2), while 19 (28.8%) were overweight or obese (BMI ≥ 25 kg/m2). In the overall cohort, the most common primary concern was preventing weight loss [in 20/66 patients (30.3%)], but there were significant differences by BMI (p < 0.001), with the most common concern in the overweight subgroup being preventing weight gain. Fifteen (46.9%) men (BMI mean 20.7, range 16.4–29.2 kg/m2) listed preventing weight loss as the primary concern, compared to only 5 (14.7%) women (BMI mean 18.4, range 16.2–19.9 kg/m2), representing a trend toward a difference in primary concerns by gender (p = 0.066).The most commonly desired health-improvement resource was online CF nutrition and fitness information, found in 26 patients (39.4%) in the overall cohort, without significant differences by BMI (p = 0.814) or gender (p = 0.199). Financial assistance was the preferred resource in 17 (26.2%), without differences by socioeconomic status (p = 0.367).ConclusionsWe identified a wide variety of nutritional needs in CF adults, including a high prevalence of overweight status, many patients desiring weight loss, and many seeking financial resources. Our findings support the individualization of modern-day CF nutrition programs and development of online resources, in an effort to address the heterogeneous barriers that exist in the contemporary CF population and improve outcomes in patients with the disease.

Dental and periodontal manifestations in patients with cystic fibrosis - A systematic review

BackgroundThe oral cavity is an important reservoir of microorganisms and can be a potential source of infection of the respiratory tract in CF patients. The literature on the oral health does not explicitly determine dental problems in these patients. The aim of the study was to systematically review the studies relating to oral status in CF patients. MethodsA systematic review of papers published from 1997 to 2018 regarding oral status in CF children and adults, carried out in accordance with the Cochrane Collaboration guidelines. ResultsThe search resulted in 143 studies. Thirteen publications were included in the systematic review. Conclusions1.Equal or a higher prevalence and more severe enamel defects in permanent dentition in CF patients, compared to healthy people, require a targeted dental care.2.The presented data show an equal or lesser caries risk in CF patients compared to the control group, but future research should focus on caries prevalence evaluation and assessing the relationship between caries experience and the enamel defects prevalence in CF adults.3.The available data cannot provide an objective assessment of the possible relationship of periodontal conditions with cystic fibrosis. The literature dealing with these issues is based solely on clinical trials but does not take into account, specialized tests, such as microbial analyses of dental plaque and saliva.4.There is a need to develop standards of dental care not only for children but also for adults, mainly to reduce the risk of autoinfection in CF patients.

137 Transcutaneous ear probe oxygenation readings are significantly higher than finger probe oxygenation readings in CF adults

Objectives: Accurate assessment of oxygen saturations (SaO2) is vital in the management of people with CF. Capillary blood gases (CBGs) are relatively painless and correlate well with arterial blood gases (ABGs) when estimating SaO2 in chronic lung disease [1]. Finger probe pulse oximetry (SpO2) is routinely used to estimate SaO2, but over the last 12 months we have started using ear probe pulse oximetry in our large regional CF centre. Our objective was to compare SaO2 by CBG or ABG with finger and ear probe SpO2 in adults with CF and normal controls. Methods:We performed simultaneous CBG or ABG, finger and ear probe SpO2 in adults with CF and normal controls. Finger and ear probe SpO2 were recorded by the same oximeter (Nonin Medical Inc.) using the appropriate sensors. Results: 21 sets of observations (19/21 CBGs) were recorded in 14 patients (6 male, mean age 29yrs, mean FEV1 30% predicted). 3 sets of observations (3/3 CBGs) were performed in 3 normal controls (1 male, mean age 31yrs). In patients ear probe SpO2 was significantly higher than finger probe SpO2 (*p < 0.001) and finger probe SpO2 was significantly lower than SaO2 (^p =0.01).

Clinical outcomes associated with Staphylococcus aureus and Pseudomonas aeruginosa airway infections in adult cystic fibrosis patients.

BackgroundStaphylococcus aureus (SA) is the most prevalent organism infecting the respiratory tract of CF children, and remains the second most prevalent organism in CF adults. During early childhood, SA infections are associated with pulmonary inflammation and decline in FEV1, but their clinical significance in adult CF patients is poorly characterized.MethodsWe conducted a retrospective cross-sectional study to determine the association between airway microbiology and clinical outcomes (FEV1, rate of pulmonary exacerbations, CRP levels and clinical scores).ResultsIn a cohort of 84 adult CF patients, 24 % were infected with SA only, 60 % were infected with PA, and 16 % had neither PA nor SA. CF patients with SA experienced fewer pulmonary exacerbations and lower CRP levels than those with PA.ConclusionIn adult CF patients, SA infections alone, in the absence of PA, are a marker of milder disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0062-7) contains supplementary material, which is available to authorized users.

153 The 15 m Shuttle Test is a valuable alternative to conventional shuttle tests in some CF patients

Background There are several tests available for the long-term evaluation of exercise capacity. Of these tests, the 10 m and 20 m Shuttle Tests can be performed in CF patients but they may be either too short or too long in patients who are doing fine or who are very ill, respectively. The aim of this study was to assess the feasibility of a 15 m Shuttle Test (15MST) in CF children, adults and lung transplant recipients (LTR). Methods and Patients Forty-one stable patients performed a 15MST: 19 CF children (FEV1 83±13% pred), 16 CF adults (FEV1 67±23%) and 6 LTR (FEV1 83±14%). Results In CF children, level variability (LV) was between 4 and 12, performed distance was 654±253 m, extrapolated VO 2 max (eVO 2 max) was 43±3 ml/kg/min, heart rate (HR) was 133±15 bpm, SaO 2 was 97±1% and dyspnea score (Borg Scale) was 5±3. In CF adults, LV was between 2 and 10, performed distance 611±334 m, eVO 2 max 30±6 ml/kg/min, HR 159±17 bpm, SaO 2 89±6% and dyspnea score 8±1. In LTR, LV was between 2 and 5, performed distance 330±117 m, eVO 2 max 20±13 ml/kg/min, HR 140±14 bpm, SaO 2 96±1% and dyspnea score 8±1. Conclusion The 15MST is feasible and usable in CF children and adults as well as LTR patients. It can be an alternative to 10 m and 20 m Shuttle Tests but it must still be validated. This work was supported by a grant from the Belgian Cystic Fibrosis Association and is part of our educational project ‘Just move it! move it!'.

273 Influenza vaccination in CF adults: Coverage level and adverse reactions

Objectives Influenza increases morbidity in CF individuals. Annual vaccination against influenza is a recommended measure in people with chronic respiratory diseases including CF. However, there are worries about adverse reactions of influenza vaccine in some patients and coverage level is generally low in the Czech Republic (approximately 5% of population). Methods We conducted a study in CF adults in Prague CF Centre regarding to coverage level and occurrence of adverse reactions after influenza vaccination using interviews during visits of CF clinic or by phone or e-mail in January 2015. Results 112 CF adults (59 males) with mean±SD age 27.3±6.2 years and mean±SD FEV 1 68±26 pred. were interviewed. Thirty-two (28.6%) patients received influenza vaccine. Among them, three patients experienced adverse reaction of mild intensity. In those who did not received a vaccination, eleven subjects reported adverse reactions in the past (two of them described it as severe), four patients experienced prolonged pulmonary exacerbations and others (58.0% of study group) had no interest in vaccination. Together, current or previous adverse reactions were reported in 14 (12.5%) subjects. Level of vaccination was not associated with sex, age or lung function. Conclusion Coverage level of influenza vaccination in Czech CF adults is low. The main reason is no interest for vaccination. Adverse reactions were quite frequent but usually with only mild intensity.

EPS05.4 A multidisciplinary approach can improve a low BMI in adults with cystic fibrosis

Objectives A quality improvement program was implemented, targeting those CF adults most at nutritional risk. Monthly MDT meetings solely focussing on adults with a BMI ≤19 have been in practice for 1 year. This study aims to assess the effectiveness of this systematic, proactive approach in improving BMI and the interventions initiated. Method Identified 24/200 CF adults with a BMI ≤19 and tracked over a 12 month period. These were discussed within a monthly meeting led by the dietitians with physicians, psychologist, social worker, and specialist nurses in attendance. Initially, a summary of each individual's nutritional history and previous dietetic interventions were presented. Most of the cohort had a long standing low BMI despite considerable dietetic input. Common reasons for this were poor tolerance to oral nutrition support (ONS) and a resistance to weight gain. Results 24 low BMI CF adults were identified (F = 10; PI=24; CFRD at baseline=11) with mean age of 23.7 years (SD = ±5.9). Mean BMI at baseline was 17.48 (±1.33). At the end 18.76 (±1.73), p=0.0002. Nutritional interventions implemented within the 12 months were: ONS (n = 4), gastrostomy feeding (n = 3), insulin (n = 1), Continuous Glucose Monitoring (n = 6) and appetite stimulant (n = 8). Other interventions included psychological support, anti-depressants, admission, IV antibiotics and more frequent MDT review. The mean follow up period was 11.4 (range 9–12) months. Conclusion Valuable support and holistic input from the CF MDT in conjunction with the CF dietitians led to successful improvement in BMI. Clinicians support with providing consistent messages was valuable.

172 Does the 60-minute OGTT value have clinical significance in CF adults?

Objectives The 120 minute Oral Glucose Tolerance Test (OGTT) is the recommended diagnostic test for CF related diabetes (CFRD). In children, higher glucose levels 60 minutes after glucose challenge correlate with worse lung function and predict future development of CFRD. We examined whether a 60 minute glucose value could be used to identify patients at risk of clinical decline in adults with CF, who may benefit from early insulin treatment. Methods Correlation was sought between OGTT values at 0, 60 and 120 minutes and FEV1, Body Mass Index (BMI), number of days of IV antibiotics and glycosylated haemoglobin (HbA 1c ) in 83 adults attending the Bristol Adult CF Centre. In 14 cases in which 60 minute glucose was ±T1.1 mmol/L, repeated measures ANOVA/Friedman test were used to test for change in FEV1, BMI and number of IV days 1 year before, at the time of, and 1 year after the OGTT. Results There was no correlation between 0, 60 or 120 minute glucose and FEV 1 , BMI or IV days. There was a weak positive correlation between HBA 1C and 0, 60 and 120 minute glucose. In the patients with 60 minute glucose 11.1 mmol/L there were no changes in FEV 1 , BMI or number of IV days over two years (see table). Year −1Year 0Year +1Significant change over time?%predicted FEV 1 , mean±SD83±2183±1983±19No, p=0.57BMI, mean±SD24±4.424±4.124±3.9No, p=0.64IV Days, sum (median)219 (14)183 (0)186 (0)No, p=0.85 Conclusion The 60 minute glucose value does not correlate with FEV 1 , BMI or IV days in our adult population and does not identify patients who will clinically decline over the next year. Its use as a routine test is therefore questionable and newer tests such as CGMS may be of more value.

279 Prevalence of pain in adults with CF with and without lung transplantation

Aim Pain symptoms are part of daily life in adults with CF, with an important impact on QOL. The aim of this study is to compare the prevalence of pain in adults with CF, with and without lung transplantation (TX). Method A cross-sectional, descriptive study was performed. Patients at the outpatient clinic were asked to fill in the Cystic Fibrosis Questionnaire; Brief Pain Inventory – short form and McGill questionnaire. Clinical data were collected from the patients files. Results From 90 participants, 50 were non-transplant CF patients. 59 participants were homozygous for DF 508, 28 heterozygous and 3 carried other mutations. CharacteristicValueTransplantationNo transplantationMales (n = 12)Females (n = 28)Males (n = 29)Females (n = 21)Mean age, y34.58 (10.457)34.96 (9.845)28.28 (8.035)29.81 (6.030)Mean FVC, %77.67 (14.606)86.07 (16.673)91.07 (20.190)85.24 (17.085)Mean FEV1, %73.50 (26.916)72.46 (22.128)68.83 (22.901)64.14 (21.618)Acute pain, n (%)2 (17%)8 (29%)11 (38%)6 (29%)Daily pain, n (%)7 (58%)16 (57%)13 (45%)9 (43%)Values are mean (SD) unless otherwise noted. Values are mean (SD) unless otherwise noted. Conclusion From all male participants 32% reported acute pain (17% TX), 56% reported daily pain (7% TX). 29% of female participants reported acute pain (29% TX), 51% daily pain (57% TX) with important impact on daily life. In TX men there was a reduced frequency of acute pain as compared to non-TX men with CF, but this difference was not significant (p = 0.27). In women, there was no difference in frequency of pain reporting between TX and non-TX patients. Pain is frequent in all CF adults and should be assessed frequently. LungTX does not result in an improvement of pain reporting. Further research is needed to implement a patient-centered pain-management system.