Adult Cystic Fibrosis Patients Research Articles

A Systematic Review on the Efficacy and Safety of the Combination of Elexacaftor, Tezacaftor, and Ivacaftor in Patients with Cystic Fibrosis

Introduction: Elexacaftor/Tezacaftor/Ivacaftor is a new combination of Cystic fibrosis transmembrane conductance regulator (CFTR)-based treatment, which modulates and corrects the CFTR protein. Several recent clinical trials reported promising responses to this combination of treatment among cystic fibrosis patients. Aim: This systematic review aims to evaluate the safety and efficacy of the combination of Elexacaftor, Tezacaftor, Ivacaftor in cystic fibrosis patients. Methods: Three healthcare-related databases were searched, namely, PubMed, Cochrane registry for clinical trials, cumulative index of nursing and allied healthcare literature (CINAHL). Search was conducted based on the relevant keywords and medical subject headings (MeSH). These search results were searched for duplications and removed if any, thereafter, these studies underwent superficial (based on title and abstract) screening and thorough screening (based on the full-text study) according to the inclusion and exclusion criteria. Finally, six clinical trials were selected from which the efficacy and safety data were collected. Furthermore, risk of bias data was collected based on the JADAD scale. Results: Six clinical trials were included with total with 994 cystic fibrosis patients, 542 were recipients of combination of Elexacaftor, Tezacaftor and Ivacaftor and 452 cystic fibrosis patients received placebo in the control arm, including one single-arm study with 66 patients, who received only triple combination therapy. Three studies included F508del homozygous while three studies included heterozygous patients. Four clinical trials were conducted among adult (>20 years) and two were conducted among child patients. All six trials reported higher ppFEV1 among the triple combination therapy recipients ranging from 9.5% to 13.6%. Furthermore, reduced sweat chloride concentration was reported by 5 out 6 clinical trials, ranging from -33.3 to -60.9 point. Moreover, health-related quality of life improvement was reported by higher CFQ-R RD (cystic fibrosis questionnaire-revised respiratory domain) ranging from 5.9 to 21.9 points. Regarding safety, better nutritional status was reported with BMI change ranging from 0.58 to 1.24, however, there were no difference in pulmonary exacerbations and adverse effect in these two arms. Pulmonary exacerbations ranged from 1.7% to 65% while adverse effects ranged from 28.9% to 93.4%. The clinical trials with child patients reported similar to ppFEV1, higher reductions in sweat chloride concentration, lower CFQ-R RD values, and much higher rates of adverse effects compared adult cystic fibrosis patients. Conclusion: This systematic review showed that combination of Elexacaftor, Tezacaftor, and Ivacaftor is more efficacious than placebo in cystic fibrosis patients. This review also reported that there was no difference in adverse effect or pulmonary exacerbations between these two arms, however, there is different trend in efficacy and safety of child and adult cystic fibrosis patients. EWMCJ Vol. 13, No. 1, January 2025: 4-16

Outcomes of Modulator Therapy Discontinued After Short-Term Use in Adult Cystic Fibrosis.

Cystic fibrosis transmembrane conductance regulator modulator therapies (CFTR-MT) have altered management, reducing exacerbations and slowing pulmonary function decline. Nevertheless, it is still uncertain if the benefits of CFTR-MTs last when they are stopped. This study aimed to assess pulmonary function changes, and exacerbation rates during and after CFTR-MT use in adult cystic fibrosis patients. Between 2018 and 2022, we conducted a study involving adult CF patients who initially used CFTR-MTs but later discontinued them due to reimbursement issues. The study was divided into three phases: predrug (T1), in-drug (T2), and postdrug (T3). We recorded pulmonary function tests, laboratory and culture results, and the number of exacerbations. The study involved 33 patients, with 28 (84.8%) receiving Elexacaftor/Tezacaftor/Ivacaftor and 5 (15.2%) receiving Ivacaftor. The median treatment and interruption durations were 3.1 (IQR = 2.9-5.7), and 2.5 (IQR = 1.5-4.0) months, respectively. The mean FEV1% was 54.3% (± 26.6), 70.4% (± 27.4), and 60.2% (± 26.5) during T1, T2, and T3, respectively (p < 0.001). The mean FVC% was 65.5% (± 23.9) in T1, increased to 81.5% (± 24.5) in T2, and decreased to 71.6% (± 25.9) in T3 (p < 0.001). The number of Psedomonas aeruginosa, and Aspergillus positive sputum cultures decreased significantly with drug use (T1: 72.7%, 39.4%; T2: 48.5%, 9.1%; T3: 45.5%, 18.2%; p = 0.014, p = 0.004, respectively). The median number of hospitalizations was 1.0 (0-5.0) in T1, 0 (0-0) in T2, and 0 (0-1.0) in T3. This study revealed that CFTR-MTs are effective even in the short term for adult CF patients, but their beneficial effects quickly diminish after discontinuation. Real-life data obtained as a result of discontinuation of drugs due to reimbursement problems has highlighted the significance of regular and uninterrupted use of modulators.

Exploring the Role of Tertiary Lymphoid Structures Using a Mouse Model of Bacteria-Infected Lungs.

Animal models can be helpful tools for deciphering the generation, maintenance, and role of tertiary lymphoid structures (TLS) during infections or tumor development. We describe here the establishment of a persistent lung infection in immune-competent mice by intratracheal instillation of agarose beads containing Pseudomonas aeruginosa or Staphylococcus aureus bacteria. After instillation, animals develop a chronic pulmonary infection, marked by the presence of TLS. This experimental setting allows the study of the function of TLS induced by bacteria encountered in patients with cystic fibrosis (CF) as P. aeruginosa and S. aureus are the two main bacterial strains that infect the bronchi of adult CF patients. Additionally, we describe also how to manipulate the immune response in these infected animals by targeting immune cells involved in TLS function. Overall, this approach makes it possible to explore the role of chronic inflammation in the induction and maintenance of TLS in infected tissues.

Systematic Review and Meta-Analysis on the Prevalence and Antibiotic Susceptibility Pattern in Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients.

This study aimed to conduct a retrospective Middle East systematic review and meta-analysis on the prevalence and antibiotic susceptibility pattern for this microorganism isolated from cystic fibrosis patients. We searched MEDLINE, the Cochrane Library, SCOPUS, and Web of Science (ISI) to identify studies that reported the prevalence of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients, and antibiotic resistance patterns. To assess the quality of publications was used of a checklist provided by the Joanna Briggs Institute. Finally, the data was analyzed by comprehensive meta-analysis software. The studied populations comprised children and young, and adult CF patients. Patients were aged between 3 months-65 years. A higher percentage of CF patients were males. Pseudomonas aeruginosa frequency varied between 5.9 and 76.2% in the studies included. The combined prevalence of P. aeruginosa was reported 34.3%. The lowest level resistance of P. aeruginosa was toward colistin (0%-13.3%) and ticarcillin (3.9%-24%). Our study showed the prevalence of P. aeruginosa and antibiotic resistance are almost high, while colistin and ticarcillin are the best antibiotics to decrease postantibiotic efects (PAEs) in CF patients from the Middle East. Therefore, physicians should pay more attention to therapeutic protocols to prevent further resistance.

7522 Effects of Trikafta On Bone Mineral Density And Body Composition In Patients With Cystic Fibrosis

Abstract Disclosure: N. Mon: None. S.S. Krishnasamy: None. G. Bakeerathan: None. L. Healy: None. E. Favier: None. S. Foushee: None. Background: Cystic fibrosis related bone disease (CFBD) is a common complication of adult Cystic fibrosis (CF) patients due to calcium, vitamin D and K malabsorption from exocrine pancreatic insufficiency, increased inflammatory cytokines, glucocorticoid therapy, delayed puberty, physical inactivity, and hypogonadism. Newer CF transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (Trikafta) has proven benefit in pulmonary and nutritional outcomes. There is limited data on effects of Trikafta on bone health and body composition. The aim is to examine the effects of Trikafta on bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), and body composition in terms of fat free mass index (FFMI) and fat mass index (FMI) in our CF patients. Method: We conducted a cross sectional and retrospective review of 38 adults with CF (Ages 20-59, 28 males and 10 females) in our CF clinic. Body Mass Index (BMI), Body composition measured by bioelectric impedance analysis, BMD of LS and FN by Dual-energy X-ray absorptiometry, Vitamin D level, and forced expiratory volume in one second (FEV1 % predicted) in patients taking Trikafta were analyzed and compared with control CF group who were not on Trikafta. Results: 38 subjects on Trikafta, aged 33.29 ± 10.36 years with FEV1 % predicted 65.11± 28.14% were studied. Serum 25-hydroxyvitamin D level was 35.92 ± 18.52 ng/dL. Of the 38 study patients, 23 (60.53%) had a diagnosis of CF related diabetes (CFRD). Among the Trikafta cohort, 18 (50%) had low BMD with Z-scores ≤ -2.0 and 7 (19.44%) of them had Z score ≤ -1.0 and &amp;gt; -2.0. Compared with the control group, LS BMD 0.93 ± 0.16 g/cm2 and FN BMD 0.73± 0.13g/cm2 (p &amp;gt;0.05) were not improved significantly. BMI of study population 23.09 ± 4.21 kg/m2 (p &amp;lt;0.05) and FMI 6.11 ± 4.25 kg/m2 (p &amp;lt;0.05) increased significantly; however, there was a decrease in FFMI 9.60 ± 1.44 kg/m2 (p &amp;lt;0.05). Conclusion: Treatment with Trikafta in CF patients was associated with increases in BMI and fat mass index but decrease in fat free mass index. There was no statistically significant difference in BMD at LS and FN in our study cohort. This study has limitations in terms of gender differences within the study cohort, duration of Trikafta use in relation to bone mass, and also extent of glucocorticoid use among the study subjects. Larger prospective clinical trials are needed to study efficacy of Trikafta on CFBD. Presentation: 6/3/2024

Self-care capacity of adult cystic fibrosis patients during transition/transfer between services

To analyze the knowledge, abilities, and emotional state of cystic fibrosis patients during a specific follow-up period and compare this with the recall they had of the transition (planned and gradual shift from the pediatric unit) / transfer (direct change skipping the steps recommended by the guidelines) to a specialized cystic fibrosis adult unit. Prospective cross-sectional study with cystic fibrosis adult patients under follow-up in a specialist consultation. Group 1 were patients who transitioned and Group 2 were transferred patients. The following information was collected: sociodemographic variables, degree of knowledge, skills, and emotional state using a survey designed for this purpose (as part of the internal consistency validation process). Participants also completed the emotional subscale of Cystic Fibrosis Questionnaire-Revised. Inter-group comparisons were made for the transition/transfer, at the follow-up, and during the evolution. Thirty-five patients were analyzed; 65.8% male; mean age 31.9 years (SD =10.1). At the transition, Group 1 (n=19; 54.3%) had greater knowledge about their medication and reduced ability to manage appointments and making decisions in comparison to Group 2 at transfer. At follow-up, Group 1 made a better report on their emotional state and significantly improved their ability to manage appointments, communication, and decision-making. Patients who were moved to an adult cystic fibrosis unit through transition were more knowledgeable about their medications. However, those who were transferred managed their appointments and decision-making better, but felt sadder.

The Association of Depression with Obstructive Sleep Apnea in Patients with Cystic and Non-Cystic Fibrosis Bronchiectasis.

Obstructive sleep apnea (OSA) and cystic fibrosis (CF) are chronic conditions that profoundly impact quality of life. OSA, characterized by repeated episodes of upper airway collapse, can exacerbate CF symptoms due to nocturnal airway obstruction. Recent studies highlight the prevalence of OSA in CF patients, especially in adults, and its detrimental effects on health and quality of life. From April 2019 to December 2021, we conducted a study with 104 bronchiectasis patients at Marmara University Pendik Training and Research Hospital. After exclusions, 70 participants (35 CF and 35 non-CF) were included. Sleep parameters were assessed with polysomnography, and depressive mood was evaluated using the Zung Self-Rating Depression Scale (SDS). Daytime sleepiness was measured using the Epworth Sleepiness Scale (ESS). The statistical analyses included t-tests, chi-square tests, and logistic regression. Among the CF patients, depressive mood was significantly associated with female sex (OR: 4.28, 95% CI: 1.27-12.04) and anemia (OR: 7.87, 95% CI: 1.50-41.27). Higher ESS scores indicated greater daytime sleepiness in the depressive groups (p = 0.051). Depressive CF patients also had a significantly longer disease duration and more frequent annual exacerbations. No significant differences were found in total sleep time, sleep efficiency, or sleep stages between the depressive and non-depressive groups. A lower forced vital capacity (FVC) was observed in the depressive CF patients, although not significantly. Depression is prevalent among adult CF patients with OSA, with significant associations with female sex and anemia. These findings underscore the need for integrated care addressing both physical and mental health aspects, including interventions for respiratory symptoms, anemia management, and sleep quality enhancement to improve overall quality of life.

Cystic fibrosis-related chronic rhinosinusitis: the key role of a comprehensive evaluation in the era of highly effective modulator therapy.

Chronic rhinosinusitis (CRS) is prevalent in cystic fibrosis (CF), significantly affecting quality of life. The introduction of CFTR modulators, including elexacaftor-tezacaftor-ivacaftor (ETI), offers promise for improving sinonasal outcomes. We conducted a retrospective cohort multicenter study analyzing electronic medical records of 45 adult CF patients with CRS, predominantly heterozygous for the ΔF508 mutation, treated with ETI between January 2018 and December 2023. Assessments included Sinonasal Outcome Test 22 (SNOT-22), Nasal Polyp Score (NPS), modified Lund-Kennedy Score (mLKS), Lund-Mackay Score (LMS), and olfactory function using smell loss visual analog scale (VAS) and Sniffin' Sticks identification test (SSIT). After 12 months of ETI therapy, significant improvements were observed in pulmonary function parameters (FEV1, FVC), CRS severity scores (SNOT-22, NPS, mLKS), radiological findings (LMS), and olfactory function. Subgroup analysis suggested enhanced efficacy in patients with prior endoscopic sinonasal surgery. ETI therapy demonstrates comprehensive improvements in CRS and olfactory function in CF patients, highlighting the potential of CFTR modulators in managing sinonasal manifestations.

Impact of Anxiety, Depression, and Coping Strategies on Health-Related Quality of Life in Patients with Cystic Fibrosis.

With the significant increase in the life expectancy of cystic fibrosis (CF) patients, many individuals now reach adulthood and develop specific coping strategies to maintain their physical and mental well-being. This study aims to evaluate coping styles and their relationship with mental health and Health-Related Quality of Life (H-RQoL) in adult CF patients. Thirty adult CF patients completed the Hospital Anxiety and Depression Scale to assess anxiety and depression, the Cystic Fibrosis Questionnaire-Revised to evaluate quality of life, and the Brief Coping Orientation to Problems Experienced questionnaire to assess coping strategies. Twelve individuals (40%) met the diagnostic criteria for being at risk of experiencing anxiety and/or depression. Anxiety risk group exhibited lower life quality scores in the domains of vitality, emotional functioning, and role limitations (P = .027, P = .001, and P = .001, respectively). Patients reporting depressive symptoms had lower scores in emotional functioning and role limitations domains of quality of life (P = .005 and P = .018, respectively). Multivariate analysis indicated that depression and anxiety scores were significant predictors of emotional quality of life. In terms of coping strategies, "acceptance" was the most commonly preferred, while "substance use" was the least preferred strategy among all participants. Patients at risk of anxiety and/or depression often chose "avoidance" as their coping strategy. Anxiety and depressive symptoms are prevalent and associated with poorer H-RQoL in adult CF patients. These patients preferred to employ giving up strategy when dealing with the disease. Therefore, it is essential to screen adult CF patients for mental health risks and to work on improving their coping strategies.

CFTR Modulators Therapy Efficacy in Reducing Cystic Fibrosis (CF) Exacerbation and Improving Selected Spirometry Parameters: A Real-Life Study in a Single-Centre Polish Population.

Background/Objectives: Cystic fibrosis is a genetically determined disease that significantly influences and shortens life. Treatment with CFTR modulators (CFTR-T) is a new hope for patients. It can change the predictive values of a poor prognosis (e.g., exacerbation rate and FEV1 value). The aim of the study was to analyse exacerbation incidence and spirometry data before and after one year (+/- 2 weeks) of CFTR-T in 85 CF patients at the CF Centre in Poznań. To our knowledge, this is the first analysis of CFTR-T efficiency in the Central-Eastern Europe population. Methods: We retrospectively analysed the spirometry and exacerbation data of 85 CF adult patients (both men and women), who in the middle of 2022 began treatment with CFTR modulators. Results: The one-year ratio of hospitalisation caused by severe exacerbations lowered from 1.25 to 0.21 per patient per year. We also saw a 66% decline in ambulatory exacerbations. The median FEV1% increased by 9.60% in absolute values and by 460 mL. Even in the group with very severe obstruction (FEV1 < 35%), there was an increase in median FEV1% of 5.9 in absolute values. We also proved the increase in FVC% (median 17.10% in absolute value and 600 mL) in the study group. Conclusions: After one year of treatment, an impressive improvement was observed in two important predictive values of poor prognosis: exacerbation rate and FEV1 values. Further observation is needed to determine how long the improvement will be present and its influence on quality of life and life expectancy.

Gut microbiota in adults with cystic fibrosis: Implications for the severity of the CFTR gene mutation and nutritional status

BackgroundMicrobial dysbiosis has been linked to cystic fibrosis (CF); however, the composition of gut microbiota in adult CF patients in relation to severity of CF transmembrane conductance regulator (CFTR) gene mutation and nutritional status have not yet been explored. Study aimed to assess the gut microbiota composition in adults with CF, and its relationship with the severity of CFTR mutations, and BMI. MethodsGut microbiota of 41 adults with CF, and 26 non-CF controls were compared using whole 16S rRNA gene sequencing. Differences in the microbial community between groups of patients classified according to the severity of CFTR mutations, and BMI were assessed. The alpha diversity, beta diversity, and taxa abundance were identified to reflect gut microbiota composition. ResultsResults showed a significant decrease in alpha diversity of bacterial communities in CF compared to non-CF group, but no significant difference between the CF groups distinguished by the severity of CFTR mutations. However, more severe mutations were associated with the higher relative abundance of Bacteroides and Streptococcus and the lower relative abundance of Faecalibacterium and Blautia. Undernourished CF patients showed significantly lower alpha diversity compared to non-CF group and CF patients with BMI within the norm. Significant differences in the structure of the gut microbiota between CF and non-CF groups, as well as between BMI groups were also found. ConclusionsOur research indicates that CF is associated with alterations in gut microbiota in adults. Additionally, in adult CF patients, the composition of the gut microbiota is also related to BMI.

Effect of Modulator Therapies on Nutritional Risk Index in Adults with Cystic Fibrosis: A Prospective Cohort Study.

Background: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF patients receiving modulator (MT) or only non-modulator (conventional) therapies (non-MT). Methods: A single-center prospective cohort study was conducted between June and December 2023. The NRI based on weight gain and albumin was calculated at beginning and end of a 12-week period in both groups. This design was pragmatic, since it was based on individual patient access to MT for 12 weeks. Results: In total, 107 patients were included [mean (SD) age: 23.85 (4.98) years, 54.7% male, 46.7% MT]. In the MT group, mean (SD) weight (kg) and albumin (g/dL) increased significantly [changes: +3.09 (2.74) and +0.17 (0.37); p < 0.001]. In the non-MT group, weight and albumin decreased significantly [changes: -0.99 (1.73) and -0.12 (0.30); p < 0.001]. Compared to the MT group, baseline mean (SD) NRI in the non-MT group was significantly higher [100.65 (11.80) vs. 104.10 (10.10); p = 0.044]. At the end of the 12 weeks, mean (SD) NRI in the MT group was higher than in the non-MT group [104.18 (10.40) vs. 102.58 (12.39); p = 0.145]. In the MT group, the NRI category improved in 22 (44%), and worsened in 3 (6%) patients (p < 0.001). In the non-MT group, the NRI category improved in 2 (3.5%), and worsened in 10 (17.5%) patients (p < 0.001). Conclusions: This is the first study reporting on a positive effect of MT on NRIs, based on weight gain and albumin. Personalized nutrition and routine follow-up of adults with CF based on NRI is recommended prior to MT initiation.

Subclinical vascular, hemodynamic and arterial stiffness changes in adults with cystic fibrosis: cross-sectional observational study

Cardiovascular diseases can be an emerging complication in cystic fibrosis (CF), as the median life expectancy has improved considerably. The objective of this study was to compare vascular, hemodynamic parameters and arterial stiffness in adult CF patients with healthy participants pared by sex and age, and to assess the factors associated with arterial stiffness in the CF group. This is a cross-sectional observational study. The evaluation of cardiovascular parameters was performed non-invasively using Mobil-O-Graph. 36 individuals with CF and 35 controls were evaluated. The mean arterial pressure (96.71 ± 10.98 versus 88.61 ± 7.40 mmHg, p = 0.0005), cardiac output (4.86 ± 0.57 versus 4.48 ± 0.44 L/min, p = 0.002) and systolic volume (64.30 ± 11.91 versus 49.02 ± 9.31 ml, p < 0.0001) were significantly lower in the CF group. The heart rate was higher in the CF when compared to the control (77.18 ± 10.47 versus 93.56 ± 14.57 bpm, p < 0.0001). The augmentation index (AIx@75) was higher in the CF than control (29.94 ± 9.37 versus 16.52 ± 7.179%, p < 0.0001). In the multivariate model controlled by body mass index and Forced Expiratory Volume in the first second, central systolic blood pressure and reflection coefficient directly related to AIx@75. Negatively related to AIx@75 were age and systolic volume. The adjusted determination coefficient was 87.40%. Individuals with CF presented lower arterial blood pressures and changes in cardiac function with lower stroke volume and cardiac output. The AIx@75, an indirect index of arterial stiffness and direct index of left ventricular overload, is increased in this population. The subclinical findings suggest the need for earlier cardiovascular assessment in this population due to increased risks of cardiovascular disease.

P355 Long-term impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on weight gain and body composition in adult cystic fibrosis patients: a retrospective analysis

P355 Long-term impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on weight gain and body composition in adult cystic fibrosis patients: a retrospective analysis

P137 Clinical characteristics of adult cystic fibrosis (CF) patients in Kazakhstan

P137 Clinical characteristics of adult cystic fibrosis (CF) patients in Kazakhstan

P340 Despite an unchanged energy intake, both pediatric and adult cystic fibrosis (CF) patients experienced improvement in their body mass index (BMI) under ETI modulator therapy

P340 Despite an unchanged energy intake, both pediatric and adult cystic fibrosis (CF) patients experienced improvement in their body mass index (BMI) under ETI modulator therapy

P032 CFTR gene variants in the group of adult cystic fibrosis patients in Kazakhstan

P032 CFTR gene variants in the group of adult cystic fibrosis patients in Kazakhstan

Improved Nutritional Outcomes and Gastrointestinal Symptoms in Adult Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor

Introduction: Cystic fibrosis transmembrane conductance regulator modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with cystic fibrosis (CF) on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. Methods: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. Results: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only 1 patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 μg/g to 442.1 μg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). Conclusion: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

Evaluating the contribution of the Glittre-ADL test in adults with cystic fibrosis.

Cardiopulmonary and skeletal muscle impairment and poor physical activity are potential contributors to reduced functional capacity in cystic fibrosis (CF). The Glittre-ADL test (TGlittre) has great potential for clinical use in adult CF adults, as it meets the need for a comprehensive assessment of physical function using tasks similar to activities of daily living. This study aimed to evaluate the performance of TGlittre in CF adults compared to the 6-min walk test (6MWT) and, secondarily, to quantify the associations of their results with pulmonary function, muscle strength, and health-related quality of life (HRQoL). This cross-sectional study evaluated 34 CF adults and compared them with 34 subjects from a control group. The participants underwent the following assessments: functional capacity using TGlittre and 6MWT; spirometry; respiratory muscle strength; handgrip strength (HGS); and HRQoL using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). While CF patients showed a longer time to perform TGlittre compared to controls (134 (119-150) versus 107 (95-126) % of the predicted time p=0.0002), no difference between these groups was observed in the 6MWT. When the second TGlittre was compared to the first TGlittre, there was a significant decrease in total time for both CF patients (p<0.0001) and controls (p=0.0001). TGlittre time correlated with 6MWT distance (6MWD) (rs=-0.641, p<0.0001), HGS (rs=-0.364, p=0.034), peripheral oxygen saturation at the end of the test (rs=-0.463, p=0.006) and the "digestive symptoms" domain of CFQ-R (rs=0.376, p=0.028). TGlittre time was shorter in patients who engaged in regular physical activity (3.10 (2.49-3.39) min versus 3.28 (2.95-3.53) min, p=0.016). TGlittre is more effective than the 6MWT in detecting limitations during exercise. There is an important learning effect of TGlittre in adult CF patients. TGlittre time was correlated with 6MWD, HGS, oxygen saturation level, and the patient's level of physical activity.

Ecological patterns and processes of temporal turnover within lung infection microbiota

BackgroundChronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical ‘one microbe, one disease’ concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota.ResultsThe lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend’s rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function.ConclusionsOur work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases.AWnQWdeG2wJZnAAmwW9_w-Video