Outcomes In Cystic Fibrosis Patients Research Articles

P154 Fertility and pregnancy outcomes in cystic fibrosis patients on CFTR modulators era: insights from Portugal

P154 Fertility and pregnancy outcomes in cystic fibrosis patients on CFTR modulators era: insights from Portugal

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d=18), a frailty index (FI, d=66) and a lifestyle/social vulnerability index (LSVI, d=10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Survival difference between high-risk and low-risk CFTR genotypes after lung transplant.

While cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with clinical outcomes in cystic fibrosis patients, it is unknown if genotype impacts lung transplant outcomes. We sought to compare lung transplant survival and time to bronchiolitis obliterans syndrome (BOS) between high-risk, low-risk, and not yet classified CFTR genotypes. We used merged data from the Organ Procurement and Transplantation Network (2005-2017) and United States Cystic Fibrosis Foundation Patient Registry (2005-2016). Cox Proportional Hazards models compared graft failure after lung transplant and time to BOS among high-risk, low-risk, and not yet classified risk CFTR genotype classes. Among 1,830 cystic fibrosis lung transplant recipients, median survival for those with low-risk, high-risk, and not yet classified genotype was 9.83, 6.25, and 5.75 years, respectively. Adjusted Cox models showed recipients with a low-risk genotype had 39% lower risk of death or re-transplant compared to those with high-risk genotype (adjusted HR 0.61, 95% CI=0.40, 0.91). A subset of 1,585 lung transplant recipients were included in the BOS subgroup analysis. Adjusted analyses showed no significant difference of developing BOS among high-risk, low-risk, or not yet classified genotypes. Lung transplant recipients with low-risk CFTR genotype have better survival after transplant compared to recipients with high-risk or not yet classified genotypes. Given these differences, future studies evaluating the mechanism by which CFTR genotype affects post-transplant survival could identify potential targets for intervention.

The effect of the cystic fibrosis care center on outcomes after lung transplantation for cystic fibrosis

The purpose of this study was to evaluate outcomes in people with cystic fibrosis (CF) who underwent lung transplant (LT) at a transplant center with an accredited Cystic Fibrosis Care Center (CFCC) in the United States. We reviewed the Scientific Registry of Transplant Recipients for all adult patients with CF who received a first-time LT from 2005 to 2018. The primary outcome was graft failure. Unadjusted Kaplan-Meier analysis and adjusted multilevel Cox proportional hazards models were used to evaluate outcomes in CF patients undergoing lung transplantation at a CFCC. 2,573 patients with CF underwent a first time LT during the study period. Of the 68 lung transplantation centers, 50 were CFCCs (73.5%). After adjustment for potential confounders, patients who underwent lung transplantation at a hospital with an accredited CFCC had a 33% reduction in risk of death or re-transplantation compared to those transplanted at a hospital without an accredited CFCC (HR: 0.67, 95% CI: 0.56-0.82, p < 0.001). People with CF who undergo LT at a transplant center with a CFCC have improved graft survival and decreased need for re-transplantation compared to those who undergo LT at a non-CFCC, independent of volume.

Non-invasive ventilation is associated with long-term improvements in lung function and gas exchange in cystic fibrosis adults with hypercapnic respiratory failure

BackgroundNon-invasive ventilation (NIV) is an established treatment option for cystic fibrosis (CF) patients with type 2 respiratory failure but the benefits of this therapy remain unclear. This study examined the long-term outcomes and response to NIV in a large adult CF cohort. MethodsAll patients attending a UK adult CF Centre receiving NIV as treatment for hypercapnic respiratory failure over a nine-year period were studied prospectively. Detailed clinical data was recorded and longitudinal data measurements were examined for the three years pre and post NIV initiation to assess effect of this intervention. Results94 patients, mean age 29.9 (SD 9.7) years, percent predicted FEV1 21.5 (7.3), received NIV. All patients commenced NIV in a hospital setting. 21 remain alive, 24 received double lung transplant, 49 died without lung transplantation. NIV use was associated with a stabilisation and improvement in both FEV1 and FVC from NIV set up to three years post follow-up, in addition to an increase in body mass index and attenuation of PCO2 (all p<0.001). No single parameter was found to predict long-term NIV response but baseline PCO2 (p=0.005), CRP (p=0.004) and age (p=0.009) were identified as independent predictors of mortality. ConclusionsNIV use in CF adults is associated with improvements in lung function and attenuation of hypercapnia which is maintained for up to three years post NIV initiation. Outcomes for CF patients with severe pulmonary disease commenced on NIV have significantly improved with fifty percent of patients expected to survive for approximately five years.

Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation.

The approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect the susceptibility profiles of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients. This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic P. aeruginosa infection. Sputum cultures were collected annually (2011 to 2016). The primary study endpoint was the proportion of subjects whose least susceptible P. aeruginosa isolate had an aztreonam MIC that was >8 μg/ml (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and percent of predicted forced expiratory volume in 1 s (FEV1% predicted) were obtained from the CF Foundation Patient Registry and compared between subjects meeting and those not meeting the primary endpoint. A total of 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13 to 22%) met the primary endpoint each year, and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual declines in lung function were comparable for subjects meeting and those not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it. The aztreonam susceptibility of P. aeruginosa remained consistent during the 5-year study. The relationship between P. aeruginosa isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with an accelerated decline in lung function but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01375036.).

Clinical outcomes of cystic fibrosis patients with hemoptysis treated with bronchial artery embolization.

ABSTRACTObjective:Massive hemoptysis is one of the most serious complications in patients with cystic fibrosis (CF). This study aimed to evaluate the hemoptysis-free period following bronchial and non-bronchial artery embolization (BAE/non-BAE) in CF patients and to investigate predictors of recurrent bleeding and mortality by any cause. Methods:This was a retrospective cohort study of CF patients ≥ 16 years of age undergoing BAE/non-BAE for hemoptysis between 2000 and 2017. Results:We analyzed 39 hemoptysis episodes treated with BAE/non-BAE in 17 CF patients. Hemoptysis recurrence rate was 56.4%. Of the sample as a whole, 3 (17.6%) were hemoptysis-free during the study period, 2 (11.8%) underwent lung transplantation, and 3 (17.6%) died. The median hemoptysis-free period was 17 months. The median hemoptysis-free period was longer in patients with chronic infection with Pseudomonas aeruginosa (31 months; 95% CI: 0.00-68.5) than in those without that type of infection (4 months; 95% CI: 1.8-6.2; p = 0.017). However, this association was considered weak, and its clinical significance was uncertain due to the small number of patients without that infection. Conclusions:BAE appears to be effective in the treatment of hemoptysis in patients with CF.

Nocturnal non invasive ventilation in normocapnic cystic fibrosis patients: a pilot study.

Background and aim:In patients with cystic fibrosis (CF) non-invasive ventilation (NIV) improves lung mechanics and gas exchange, and decreases the work of breathing. Domiciliary NIV is mainly used in hypercapnic patients with severe disease, because it counteracts the progression of lung functional impairment and it is often used as a useful “bridge” to lung transplantation. However, to date, there are no standardized criteria to indicate the effect of a precocious starting of NIV in patients with functional ventilation inhomogeneity without hypercapnia. In this pilot study we assessed whether an early NIV treatment might influence functional and clinical outcomes in CF patients.Methods:Six normocapnic CF patients were treated for one year with NIV. At baseline and after 1 year of NIV treatment, arterial gas analysis, spirometry, MBW to derive LCI, nocturnal cardio-respiratory polygraphy (PG), and Pittsburgh Sleep Quality Index (PSQI) were perfomed in all enrolled patients.Results:After one year, despite spirometric and LCI values remain statistically not modified, the number of infectious exacerbations was reduced by 50%.Conclusions:These results suggest that nocturnal NIV improves clinical conditions of stable CF patients. Finally, we suggest that this procedure can be useful to counteract the progression of lung disease even in normocapnic patients (www.actabiomedica.it)

P131 Most of Staphylococcus aureus and Pseudomonas aeruginosa coinfecting isolates coexist, a condition that may impact clinical outcomes in cystic fibrosis patients

P131 Most of Staphylococcus aureus and Pseudomonas aeruginosa coinfecting isolates coexist, a condition that may impact clinical outcomes in cystic fibrosis patients

Structural determinants of long-term functional outcomes in young children with cystic fibrosis.

Accelerated lung function decline in individuals with cystic fibrosis (CF) starts in adolescence with respiratory complications being the most common cause of death in later life. Factors contributing to lung function decline are not well understood, in particular its relationship with structural lung disease in early childhood. Detection and management of structural lung disease could be an important step in improving outcomes in CF patients. Annual chest computed tomography (CT) scans were available from 2005 to 2016 as a part of the AREST CF cohort for children aged 3 months to 6 years. Annual spirometry measurements were available for 89.77% of the cohort (167 children aged 5-6 years) from age 5 to 15 years through outpatient clinics at Perth Children's Hospital (Perth, Australia) and The Royal Children's Hospital in Melbourne (Melbourne, Australia) (697 measurements, mean±sd age 9.3±2.1 years). Children with a total CT score above the median at age 5-6 years were more likely to have abnormal forced expiratory volume in 1 s (FEV1) (adjusted hazard ratio 2.67 (1.06-6.72), p=0.037) during the next 10 years compared to those below the median chest CT score. The extent of all structural abnormalities except bronchial wall thickening were associated with lower FEV1 Z-scores. Mucus plugging and trapped air were the most predictive sub-score (adjusted mean change -0.17 (-0.26 - -0.07) p<0.001 and -0.09 (-0.14 - -0.04) p<0.001, respectively). Chest CT identifies children at an early age who have adverse long-term outcomes. The prevention of structural lung damage should be a goal of early intervention and can be usefully assessed with chest CT. In an era of therapeutics that might alter disease trajectories, chest CT could provide an early readout of likely long-term success.

2663. Impact of Pre-Transplant Microbiology on Acute Outcomes in Cystic Fibrosis Patients Receiving Bilateral Lung Transplants

BackgroundLung transplantation is a life-prolonging intervention for cystic fibrosis (CF) patients; however, their tendency to be colonized with multiple respiratory pathogens poses a unique risk for post-transplant complications. While infections with certain CF-related pathogens have been identified as contraindications for transplant, much remains uncertain about the influence of pre-transplant microbiological factors on post-transplant outcomes.MethodsA retrospective cohort study was performed for all CF patients receiving bilateral lung transplants at a single center during the 2016–2018 period. Patient and microbiological data were collected and analyzed from 1 year pre-transplant to 3 months post-transplant. Patients were categorized according to pre-transplant microbiology, with consideration to multidrug-resistant organisms (MDROs) and chronic organisms (positive culture in ≥ 50% of encounters).ResultsTwenty-seven CF patients received a transplant during this time period. Twenty-five patients (92.6%) had re-isolation with ≥ 1 pre-transplant organism in the 3 month period post-transplant, with 16 (59.3%) developing infectious complications, and 11 (40.7%) developing rejection. Isolates associated with chronic infections were the principal factor in determining re-isolation post-transplant (OR = 4.353, 95% CI = 1.455–13.027, P = 0.009). Multidrug-resistance (P = 0.095) and species (P > 0.3) were not significant predictors of re-isolation. There was no difference in early post-transplant outcomes (infectious complications, rejection, FEV1% predicted, ICU and hospital LOS) for patients chronically infected with MDROs vs. those who were not (P > 0.3). Chronic infections with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus were not predictors of poor outcomes (P > 0.3). However, chronic fungal infections (n = 7) produced more infectious complications (median 2 vs. 0, P = 0.0453) and longer ICU stays (median 22 days vs. 5 days, P = 0.0191).ConclusionChronic infections are associated with a greater risk of post-transplant re-isolation of pathogens in CF patients, more so than drug resistance or species. Chronic infections with fungi were associated with worse transplant outcomes.Disclosures All authors: No reported disclosures.

P263 Key outcomes in cystic fibrosis patients treated with Orkambi for 12 months: real-world data from the Irish Cystic Fibrosis Registry

P263 Key outcomes in cystic fibrosis patients treated with Orkambi for 12 months: real-world data from the Irish Cystic Fibrosis Registry

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR.

The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. ClinicialTrials.gov, NCT01521338. CFF Therapeutics (GOAL11K1).

In vitro activity of N-acetylcysteine against Stenotrophomonas maltophilia and Burkholderia cepacia complex grown in planktonic phase and biofilm.

Stenotrophomonas maltophilia and Burkholderia cepacia complex (Bcc) have been increasingly recognized as relevant pathogens in hospitalized, immunocompromised and cystic fibrosis (CF) patients. As a result of complex mechanisms, including biofilm formation and multidrug resistance phenotype, S. maltophilia and Bcc respiratory infections are often refractory to therapy, and have been associated with a worse outcome in CF patients. Here we demonstrate for the first time that N-acetylcysteine (NAC), a mucolytic agent with antioxidant and anti-inflammatory properties, may exhibit antimicrobial and antibiofilm activity against these pathogens.The antimicrobial and antibiofilm activity of high NAC concentrations, potentially achievable by topical administration, was tested against a collection of S. maltophilia (n = 19) and Bcc (n = 19) strains, including strains from CF patients with acquired resistance traits. Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs) ranged from 16 to 32 mg/ml and from 32 to >32 mg/ml, respectively. Sub-MIC concentrations (i.e., 0.25 × MIC) slowed down the growth kinetics of most strains. In time-kill assays, 2-day-old biofilms were more affected than planktonic cultures, suggesting a specific antibiofilm activity of NAC against these pathogens. Indeed, a dose- and time-dependent antibiofilm activity of NAC against most of the S. maltophilia and Bcc strains tested was observed, with a sizable antibiofilm activity observed also at 0.5 and 1 × MIC NAC concentrations. Furthermore, at those concentrations, NAC was also shown to significantly inhibit biofilm formation with the great majority of tested strains.

Insights into the genome diversity and virulence of two clinical isolates of Burkholderia cenocepacia.

Burkholderia cenocepacia is among the most common members of the Burkholderia cepacia complex (Bcc) isolated from patients with cystic fibrosis (CF). The factors triggering the high rates of morbidity and mortality in CF patients are not well elucidated. In this study, we aim to highlight the genome diversity of two clinical isolates of B. cenocepacia through comparative genome analysis. The repertoire of virulence factors and resistance genes compared to reference strains J2315 and K56-2 was elucidated. The isolates were screened for the presence of phages and insertion sequences. Two methods were combined to obtain an accurate prediction of genomic islands (GIs): the cumulative GC profile and the IslandViewer web tool. To study evolutionary relatedness, whole genome-based single-nucleotide polymorphism (wgSNP) analysis was also performed with 43 publically available strains of the Bcc of various sequence types.Results/Key findings. Genome-based species identification of the two isolates BC-AUH and BC-BMEH confirmed the species as B. cenocepacia. Both belonged to ST-602, a double-locus variant of ST-32 (CC31), genomovar IIIA, and carried a large number of antibiotic resistance genes. Eighteen GIs were predicted in BC-AUH and BC-BMEH, occupying 9.3 and 6.1 % of the respective genomes. Comparison to J2315 revealed 89 and 85 genes unique to BC-BMEH and BC-AUH, respectively. Additionally, 1823 intergenic SNPs were detected between BC-BMEH and BC-AUH. This study mapped existing genetic variations in B. cenocepacia associated with notorious outcomes in CF patients, and the data obtained provide comprehensive, genome-inferred insights and multifactorial examination of an important human pathogen.

22. Immune Response to Stenotrophomonas maltophilia in Cystic Fibrosis Patients

Background: Stenotrophomonas maltophilia is one of the most common multidrug-resistant organisms isolated from the cystic fibrosis (CF) respiratory tract but it is unknown how it influences the long term clinical outcomes of CF patients.&#x0D; &#x0D; Objective/Hypothesis: To characterize the immune response to S. maltophilia and its association with clinical outcomes in CF patients over time. &#x0D; Methods: This was a longitudinal study from 2007-2014 of CF patients followed at The Hospital for Sick Children and St. Michael’s Hospital. All patients were classified as: 1) those with chronic S. maltophilia: ³2 positive cultures/year, 2) intermittent S. maltophilia: 1 positive sputum culture/year, and 3) no S. maltophilia cultures/year with and without chronic P. aeruginosa. IgG/IgA/IgM serologic responses were measured in serial sera samples by ELISA using whole cell S. maltophilia antigen. Results were calculated as the ratio of the average serum sample optical density to the average optical density of the negative control wells. Antibody levels for each patient were compared longitudinally to their rate of decline in FEV1 % predicted, body mass index, and rate of hospitalization.&#x0D; &#x0D; Results: S. maltophilia antibody levels were measured in 350 sera samples from 113 CF patients. Median baseline antibody levels were 1.56 (range 0.996-5.15) in chronic patients, 1.09 (range 0.907-3.79) in intermittent patients, and 1.12 (range 0.737-4.86) in patients with no S. maltophilia. &#x0D; Conclusions:&#x0D; Preliminary data suggests antibody levels to be significantly higher in patients with chronic S. maltophilia, and no significant difference between intermittent S. maltophilia and no S. maltophilia.

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR

Clinical outcome of cystic fibrosis patients colonized by Scedosporium species following lung transplantation: A single-center 15-year experience.

Fungi of the genus Scedosporium are emerging pathogens responsible for severe infections in lung transplant recipients. These infections are associated with poor prognosis and some centers consider now Scedosporium species colonization as a contraindication to lung transplantation (LT) even though no published evidence demonstrates that Scedosporium species colonization is associated with higher morbidity or mortality after LT. Here, we aim to describe characteristics and outcome of cystic fibrosis (CF) lung transplant recipients colonized with Scedosporium species in a single center over a 15-year period. During the study period, 14 patients had scedosporial colonization reported. Only one patient, colonized before transplantation by Lomentospora prolificans, developed scedosporial disease. Among the eight patients colonized before transplantation by Scedosporium apiospermum complex, the median survival was 1.92year (range 0.21-12.5). All these patients except one became free of fungal colonization after transplantation with antifungal prophylaxis including voriconazole or posaconazole. For the five patients colonized after LT, including two with L.prolificans, the median survival was 1.75years (range 0.1-13); three of them are still alive. It appears to us that scedosporial colonization may not be a contraindication for LT in CF patients, as long as S.apiospermum complex is involved and a life-long azole prophylaxis prescribed.

Long term outcome of cystic fibrosis patients with multisystem evaluation.

Cystic fibrosis is a chronic disease with multiple organ involvement and chiefly results in chronic respiratory infections, pancreatic insufficiency and associated complications. The age at diagnosis, clinical presentation, rate of disease progression and prognosis is variable among patients. This study is designed to evaluate the behavior of disease to provide epidemiologic data for early recognition and proper management. The study was designed as an active surveillance of 192 patients diagnosed with cystic fibrosis in a tertiary lung disease centre between 2008 and 2015. The diagnosis of cystic fibrosis was established in all patients accordingly to conventional criteria, including two positive sweat chloride tests and clinical signs and symptoms. Demographic, clinical and laboratory data were obtained from these patients in each hospitalization and also every follow-up visit and carefully evaluated for complications of this chronic disease. The majority of patients showed positive culture for Pseudomonas aeroginosa. Bronchiectasis was the most prevalent finding in chest CT scan. 44.3% of patients had been treated for allergic bronchopulmonary aspergillosis and all had sinus disease. Increased pulmonary artery pressure was observed in 40% of patients with cystic fibrosis. 33 patients died which consisted 17.1% of all the patients.The mean age of mortaliy was 18.15 year. The clinical outcome of cystic fibrosis is variable in different countries which may reflect environmental influences and the role of early diagnosis on long term outcomes. However, the role of early diagnosis in long-term outcomes of the disease can not be ignored.

Long-term work participation among cystic fibrosis patients undergoing lung transplantation

BackgroundPatients with cystic fibrosis (CF) experience obstacles to employment, regardless of whether they have undergone lung transplantation (LTx). We investigated socioeconomic and clinical factors predicting long-term employment outcomes in CF patients receiving LTx. MethodsData from the United Network for Organ Sharing registry were used to identify CF patients 18–59years-old who received LTx between 2000 and 2010 and survived greater than 5years. Long-term employment status was determined by center-reported follow-up data on patients working for income, collected at the 5th transplant anniversary. After multiple imputation to complete missing data on covariates, multivariable logistic regression was used to identify associations between characteristics at or after LTx and long-term work participation. ResultsThere were 745 patients who met inclusion criteria and contributed employment data within 365days of their 5th LTx anniversary. In this cohort, 48% (358/745) were working for income 5years after LTx. Younger age, male gender, better pulmonary function attained post-transplant, pre-transplant work participation, and private health insurance (compared to government Medicaid or Medicare insurance) at the time of transplant predicted greater odds of post-transplant employment. ConclusionsLack of work experience and reliance on government health insurance at the time of transplant predict lower long-term work participation among LTx recipients with CF. By contrast, long-term employment outcomes were not negatively affected by comorbidities at or after transplantation in this cohort. Despite resolving some physiological obstacles to employment in patients with CF, LTx may introduce new socioeconomic barriers to employment.