Adult Cystic Fibrosis Patients Research Articles

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 > -2.0. Compared with the control group, LS BMD 0.93 ± 0.16 g/cm2 and FN BMD 0.73± 0.13g/cm2 (p >0.05) were not improved significantly. BMI of study population 23.09 ± 4.21 kg/m2 (p <0.05) and FMI 6.11 ± 4.25 kg/m2 (p <0.05) increased significantly; however, there was a decrease in FFMI 9.60 ± 1.44 kg/m2 (p <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

Nutritional support for adult сystic fibrosis patients receiving targeted treatment

Cystic fibrosis (CF) is characterized by the development of a severe nutritional deficiency. A low BMI directly correlates with low lung function and requires active nutritional support. Pathogenetic (targeted) therapy aimed at restoring the chlorine channel function also leads to weight gain. The effects of CFTR modulators on extrapulmonary pathology in adult CF patients in Russia have been described very little.Aim. To evaluate the sequential impact of two targeted drugs – the potentiator ivacaftor and the triple combination of CF transmembrane regulator modulators elexacaftor/tezacaftor/ivacaftor – on the nutritional status of an adult patient with cystic fibrosis receiving nutritional support.Conclusion. Therapy with CFTR modulator in combination with sipping nutritional support promotes significant weight gain in adult CF patients. The triple combination of elexacaftor/tezacaftor/ivacaftor has a more active effect on nutritional status than ivacaftor alone. The targeted therapy requires supervision by a nutritionist.

Сhronic rhinosinusitis in adult patients with cystic fibrosis receiving CFTR modulators

Cystic fibrosis-associated chronic rhinosinusitis (CRS) is a separate form of CRS that progresses gradually over the course of patient’s life and worsens with age. The reasons for this are the mechanical congestion of mucus in the paranasal sinuses and the persistence of colonies of pathogenic antibiotic-resistant microorganisms. Therapy with CFTR modulators has resulted in a significant reduction in the severity of CRS. The nature of these changes and the dynamics in the microbial landscape of the upper respiratory tract are not sufficiently explored.Aim of the article is to highlight various aspects of the impact of CFTR modulators on the course of CRS in adult patients with cystic fibrosis (CF) based on literature data and a number of our own clinical observations. The article presents a series of clinical cases of CRS in adult CF patients treated with CFTR modulators for different periods of time.Conclusion. During targeted therapy with CFTR modulators, the symptoms of CRS are reversed due to the restoration of normal rheological properties of nasal secretions, the clinical picture improves, and the severity of CRS decreases. However, this type of treatment has no direct effect on the microbial landscape of the respiratory tract and requires additional interventions in the form of local and systemic antibacterial therapy. Therapy with CFTR modulators alters the course of CF in the nasal cavity, as well as in the pharynx and larynx.

Intracellular Pseudomonas aeruginosa within the Airway Epithelium of Cystic Fibrosis Lung Tissues.

Rationale: Pseudomonas aeruginosa is the major bacterial pathogen colonizing the airways of adult patients with cystic fibrosis (CF) and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evade the immune system and antibiotic therapy. Although the ability of P. aeruginosa to invade and survive within epithelial cells has been described invitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. Objectives: To detect and characterize intracellular P. aeruginosa in CF airway epithelium from human lung explant tissues. Methods: We sampled lung explant tissues from patients with CF undergoing lung transplantation and non-CF lung donor control tissue. We analyzed lung tissue sections for the presence of intracellular P. aeruginosa using quantitative culture and microscopy, in parallel to histopathology and airway morphometry. Measurements and Main Results: P. aeruginosa was isolated from the lungs of seven patients with CF undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P. aeruginosa within airway epithelial cells in three of the seven patients analyzed at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. Conclusions: This is the first study describing the presence of intracellular P. aeruginosa in CF lung tissues. Although intracellular P. aeruginosa in airway epithelial cells is likely relatively rare, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.

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.