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As survival and health improve in people with cystic fibrosis (CF), more women with CF (wwCF) are considering their sexual and reproductive health (SRH). This study compared SRH experiences, behaviors, and care utilization of wwCF to the general population and defined CF-impacted considerations and care preferences.We surveyed wwCF aged ≥25 years regarding SRH and compared results to the US National Survey of Family Growth (NSFG;n = 4357) and friend controls(n = 123). We used descriptive statistics and chi-squared/Fisher's exact testing and linear regression for comparisons.A total of 460 wwCF (mean age 36.1 years) completed the survey. WwCF were less likely to report current contraceptive use (43%vs76% NSFG, p0.001;60% friends, p = 0.005). Nearly 25% of wwCF reported worsened CF symptoms during their menstrual cycles, 50% experienced urinary incontinence, and 80% vulvovaginal candidiasis. WwCF were significantly less likely to be parents (46%vs62% friends, p = 0.015) and to have experienced pregnancy (37%vs78% NSFG, p0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p0.001 and 5% friends, p0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p0.001). WwCF report suboptimal rates of contraceptive and preconception counseling/care and are less likely to have received HPV vaccination (42%vs55%friends, p = 0.02). Despite desiring SRH conversations with their CF team,50% report discussing SRH topics.WwCF have significantly different SRH experiences than non-CF peers. They report suboptimal SRH care compared to their preferences highlighting an urgent need to encourage SRH counseling/care in the CF model.

BACKGROUND: Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear. METHODS: To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). RESULTS: Hypoglycemia, defined as glucose

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.METHODS: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.RESULTS: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3-1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6-1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1-1.8, p = 0.02) and episodes of acute rejection (1-2 episodes, HR = 1.5, 95% CI = 1.1-2.1, p = 0.014; 3-4 episodes, HR = 1.6, 95% CI = 1.0-2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1-4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5-0.9, p = 0.007).CONCLUSIONS: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.

Rationale: Diabetes is associated with worse cystic fibrosis (CF) outcomes. The CFTR potentiator ivacaftor is suggested to improve glucose homeostasis in individuals with CF. Objectives: To test the hypothesis that clinically indicated ivacaftor would be associated with improvements in glucose tolerance and insulin and incretin secretion. Methods: Oral glucose tolerance tests, mixed-meal tolerance tests, and glucose-potentiated arginine tests were compared preivacaftor initiation and 16 weeks postivacaftor initiation in CF participants with at least one CFTR gating or conductance mutation. Meal-related 30-minute (early phase) and 180-minute incremental area under the curves were calculated as responses for glucose, insulin, C-peptide, and incretin hormones; glucagon-like peptide-1; and glucose-dependent insulinotropic polypeptide. First-phase insulin secretion, glucose potentiation of arginine-induced insulin secretion, and disposition index were characterized by glucose-potentiated arginine stimulation tests. Measurements and Main Results: Twelve subjects completed the study: six male/six female; seven normal/five abnormal glucose tolerance (oral glucose tolerance test 1-h glucose ≥155 and 2-h glucose

BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA.METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models.RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09-3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28-3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates.CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

Purpose Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. Methods This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. Results Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). Conclusion Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR.

To help answer the question of length of intravenous antibiotics during an acute exacerbation of cystic fibrosis (CF), we had subjects to follow daily home spirometry while on intravenous antibiotics. CF patients, 18 and older, with an acute exacerbation requiring intravenous antibiotics had a daily FEV1. The average time to a 10% increase over their initial sick FEV1 was calculated, as well as the time to a new baseline. A total of 25 subjects completed the study. Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15 subjects with a sustainable 10% increase in FEV1, it took 5.2 days (±4.5) after day 1, while a new baseline was achieved on average at 6.6 days (±4.8) after day 1. Given the wide range of time to a 10% improvement and new baseline, it is recommended there should be flexibility in length of intravenous antibiotics in CF, not by a preset number.

Background Advanced cystic fibrosis lung disease (ACFLD) is common, is associated with reduced quality of life, and remains the most frequent cause of death in individuals with cystic fibrosis (CF). These consensus guidelines provide recommendations to the CF community on management of both common and unique issues that arise when individuals reach a state of ACFLD. Methods The CF Foundation assembled a multidisciplinary expert panel consisting of three workgroups: Pulmonary management; Management of comorbid conditions; Symptom management and psychosocial issues. Topics were excluded if the management considerations did not differ in ACFLD from in the overall CF population or if already addressed in other published guidelines. Recommendations were based on a systematic literature review combined with expert opinion when appropriate. Results The committee formulated twenty-three recommendation statements specific to ACFLD that address the definition of ACFLD, pulmonary and intensive care unit management, management of selected comorbidities, symptom control, and psychosocial issues. Conclusions These recommendations are intended to be paired with previously published management guidelines for the overall CF population, with the objective of reducing practice variability and improving overall care, quality of life, and survival in those with ACFLD.

Background The clinical effects of Aspergillus fumigatus in the cystic fibrosis (CF) airway, with the exception of allergic bronchopulmonary aspergillosis, is unclear. Methods CF adolescents and adults (age 14 years and older) underwent bacterial and semi-selective fungal culture testing to determine the prevalence of fungi in the CF respiratory tract and the independent association between the presence of Aspergillus fumigatus and clinical characteristics. Results Aspergillus fumigatus (10.3%) and Candida species (57.8%) were the most common filamentous fungi and yeast seen respectively in the sputa of 206 individuals with CF. Inhaled corticosteroid (ICS) use was more common in Aspergillus fumigatus-positive than Aspergillus fumigatusnegative (100% versus 75.8%, p = .01). Aspergillus fumigatus was significantly associated with lower respiratory domain score (β −8.74, 95% CI −16.6, −0.88, p = .03), representing worse respiratory-related quality of life, accounting for demographics, disease characteristics, and the presence of a pulmonary exacerbation. Conclusion The presence of Aspergillus fumigatus in CF sputum was associated with worse respiratory quality of life in CF in a crosssectional, single center study. Longitudinal analysis examining the clinical implications of Aspergillus fumigatus on respiratory health over time is needed.

BackgroundFor people with advanced stage cystic fibrosis (CF), tailored survival estimates could facilitate preparation for decision-making in the event of acutely deteriorating respiratory function.MethodsWe used the US CF Foundation national database (2008–2013) to identify adult people with incident advanced stage CF (forced expiratory volume in 1 s (FEV1) ≤45% predicted). Using the lasso method for variable selection, we divided the dataset into training and validation samples (2:1), and developed two multivariable Cox proportional hazards models to calculate probabilities of survival from baseline (T0 model), and from 1 year after (T12 model). We also performed Kaplan-Meier survival analyses.Results4752 people were included. For the T0 model, FEV1; insurance; non-invasive ventilation; supplemental oxygen; Burkholderia colonisation; cirrhosis; depression; dialysis; current smoking; unclassifiable mutation class and cumulative CF exacerbations predicted increased mortality. Baseline transplant evaluation status of ‘accepted, on waiting list’ predicted decreased mortality. For the T12 model, interim decrease in FEV1 >10%, and pulmonary exacerbations additionally increased predicted mortality. Lung transplantation was associated with lower mortality. Of the 4752, 93.5%, 86.4%, 79.7% and 73.9% survived to 1, 2, 3 and 4 years, respectively, without considering any confounding variables. The models had moderate predictive ability indicated by the area under the time-dependent receiver operating characteristic curve (0.787, 95% CI 0.769 to 0.794 for T0 model; and 0.779, 95% CI 0.767 to 0.797 for T12 model).ConclusionWe have developed models predicting survival in people with incident advanced stage CF, which can be reapplied over time to support shared decision-making about end-of-life treatment choices and lung transplantation. These estimates must be updated as data become available regarding long-term outcomes for people treated with CF transmembrane conductance regulator modulators.

Shahid Husain, MD, MS, Amparo Sole, MD, PhD, Barbara D. Alexander, MD, MHS, Saima Aslam, MD, MS, Robin Avery, MD, Christian Benden, MD, Eliane M. Billaud, PharmD, PhD, Daniel Chambers, MBBS, MD, Lara Danziger-Isakov, MD, Savitri Fedson, MD, Kate Gould, MD, Aric Gregson, MD, Paolo Grossi, MD, PhD, Denis Hadjiliadis, MD, Peter Hopkins, MD, Me-Linh Luong, MD, Debbie J.E. Marriott, MD, Victor Monforte, MD, Patricia Munoz, MD, PhD, Alessandro C. Pasqualotto, MD, PhD, Antonio Roman, MD, Fernanda P. Silveira, MD, Jeffrey Teuteberg, MD, MS, Stephen Weigt, MD, Aimee K. Zaas, MD, MHS, Andreas Zuckerman, MD, and Orla Morrissey, MD, PhD

Purpose Rates of deep vein thrombosis (DVT) range from 20-60% in patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Data on the rates of DVT in lung transplant recipients bridged with ECMO is limited. The objective of this study was to report incidence and outcomes, including use of anticoagulation and subsequent bleeding rates, of DVT in ECMO-bridged transplant recipients. Methods This was a single center retrospective cohort study of all adult ECMO-bridged lung transplant recipients from 5/1/15 to 9/30/19. Recipients underwent routine ultrasound screening for upper extremity (UE) and lower extremity (LE) DVT following ECMO decannulation. Results Of the 45 ECMO-bridged recipients, 3 died before ECMO decannulation and 4 did not have screening ultrasounds, leaving 38 patients in the cohort. The majority (81.5%) were bridged using venovenous ECMO and most (63%) were decannulated immediately following transplant (Table 1). Among remaining recipients, mean time to decannulation was 4 days. Among recipients with adequate studies, the incidence of LE DVT was 26.4% and the incidence of UE DVT was 63.6%. Neither total time on ECMO, cannula size, nor need for femoral vein cannulation was associated with LE or UE DVT. All of the recipients with LE DVT but two, were anticoagulated. Three needed an inferior vena cava filter placed. Of recipients with UE DVT only, 43.75% were anticoagulated. Among all anticoagulated recipients, five (31.25%) had significant bleeding during their initial hospitalization requiring cessation of anticoagulation. Conclusion DVTs are common in patients bridged to lung transplantation with ECMO, particularly in the upper extremity. Bleeding poses further challenges for systemic anticoagulation in this high risk population. Additional studies are needed to identify risk factors for both LE DVT and for bleeding to help guide decisions for systemic anticoagulation in this population.

Introduction Prevalence of fungi has been rising in the cystic fibrosis (CF) population. Scedosporium species (spp) is the second most common mold seen in the CF respiratory tract. However, the characteristics associated with Scedosporium isolation and its clinical implications are poorly understood. The goal of this study was to determine clinical factors associated with Scedosporium spp to better understand the mechanisms that may contribute to the emergence of filamentous fungi in CF. Methods We conducted a retrospective cohort study of subjects followed in the CF Foundation Patient Registry between January 1, 2010 and December 31, 2012. Patients under 6 years of age, history of solid organ transplantation, and insufficient respiratory culture data were excluded. We used a multivariable logistic regression model to determine demographic data and baseline disease characteristics, medications and co-infections associated with Scedosporium spp recovery in CF sputum. Results Among 19 023 subjects, prevalence of Scedosporium spp was 615 (3.2%). Older age (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07, 1.26) and white race (OR 1.69, 95% CI 1.09, 2.63) were the demographic factors associated with Scedosporium spp isolation. Inhaled antibiotic use had a significant association with Scedosporium isolation (OR 2.01, 95% CI 1.61, 2.52). For every additional course of intravenous antibiotics, the odds of Scedosporium isolation increased by 8% (OR 1.08, 95% CI 1.03, 1.14). Conclusions The association between inhaled antibiotics and Scedosporium informs us that chronic inhaled antibiotics may be playing a role in Scedosporium isolation. Further investigation to better characterize this relationship is necessary.

BACKGROUND: Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. METHODS: A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. RESULTS: Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p b 0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p b 0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p b 0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p b 0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. CONCLUSIONS: We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors.

Background DNase (Pulmozyme) effectiveness in cystic fibrosis treatment is in some cases limited by its inability to access DNA trapped within bundles in highly viscous fluids that also contain actin. Dissociating DNA-containing bundles using actin depolymerizing agents and polyanions has potential to increase DNase efficacy. Methods Fluorescence measurements of YOYO-1 and a rheological creep-recovery test quantified DNA content and viscoelasticity in 150 sputum samples from adult CF patients and their susceptibility to fluidization by DNase1, alone and in combination with gelsolin and poly-aspartate (p-Asp). Fluidization of sputum by these agents is compared to their capacity to increase antibacterial activity in sputum, measured using a luminescent Pseudomonas aeruginosa strain and a bacterial killing assay. Results The polyanion p-Asp (1–50μg/g of sputum), the actin severing protein gelsolin (10-90μg/g) and their combination enhance the ability of DNase 1 to increase the abnormally low mechanical compliance of CF sputum and to promote bacterial killing in sputum by colistin and tobramycin, two antibiotics commonly used to treat CF. Conclusions Addition of low concentrations of p-ASP or gelsolin can increase the therapeutic value of Pulmozyme (DNase 1).

Due to heterogeneity in pulmonary disease, current literature may misrepresent inspiratory muscle involvement in cystic fibrosis (CF). This study investigated inspiratory muscle strength (IMS) relative to disease severity in adults with CF.Maximal inspiratory pressure (MIP) was assessed in 58 adults with stable CF grouped by disease severity (20 mild, 20 moderate, 18 severe) and compared to 20 controls. Relationships between MIP, lung function, dyspnea and anthropometrics were evaluated using multivariable linear models.MIP in cmH2O and %-predicted was decreased in advanced CF lung disease as compared to mild disease and healthy controls (p0.05). Disease severity accounted for 24% of the variance in IMS after controlling for confounding variables (p0.001).IMS is decreased in some adults with stable CF with moderate and severe pulmonary disease, and is related to dyspnea. Future studies should determine if decreased IMS contributes inefficient breathing patterns, respiratory pump dysfunction, and/or exercise intolerance in advanced CF.

The Cystic Fibrosis (CF) Foundation developed clinical care guidelines for the prevention of Pseudomonas aeruginosa infection, the treatment of initial P. aeruginosa infection, and the use of bronchoscopy to obtain routine airway cultures in individuals with CF.A multidisciplinary committee developed questions about the prevention and treatment of initial P. aeruginosa infection and the use of bronchoscopy to obtain routine airway cultures. The outcome measure of interest was cultures without P. aeruginosa growth. Systematic reviews of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were conducted in May 2012 and August 2013. Searches combined controlled vocabulary terms and text words for CF and terms relevant to each question. The entire committee reviewed the evidence, and final recommendation statements were graded using the U.S. Preventive Services Task Force system. Recommendation 1: The CF Foundation strongly recommends inhaled antibiotic therapy for the treatment of initial or new growth of P. aeruginosa from an airway culture (certainty of net benefit, high; estimate of net benefit, substantial; grade of recommendation, A). The favored antibiotic regimen is inhaled tobramycin (300 mg twice daily) for 28 days. Recommendation 2: The CF Foundation recommends against the use of prophylactic antipseudomonal antibiotics to prevent the acquisition P. aeruginosa (certainty of net benefit, moderate; estimate of net benefit, zero; grade of recommendation, D). Recommendation 3: The CF Foundation recommends routine oropharyngeal cultures rather than bronchoalveolar lavage cultures obtained by bronchoscopy in individuals with CF who cannot expectorate sputum to determine if they are infected with P. aeruginosa (certainty of net benefit, moderate; estimate of net benefit, moderate; grade of recommendation, B).

Background The provision of effective palliative care is of great importance to patients awaiting lung transplantation. Although the prospect of lung transplantation provides hope to patients and their families, these patients are usually very symptomatic from their underlying disease. Methods An e-mail questionnaire was sent to members of the American College of Chest Physicians' Transplant NetWork and the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT). The survey included questions about barriers to providing palliative care, the availability of palliative care services, and recommended strategies to improve palliative care for lung transplant candidates. Results The 158 respondents represented approximately 65% of transplant programs in the ISHLT registry. Respondents were in practice a mean of 11.3 (± 9) years, 70% were pulmonologists, 17% were surgeons, and 13% were other care providers. Barriers were classified into domains including patient factors, family factors, physician factors, and institutional/transplant program/lung allocation system factors. Significant patient/family barriers included unrealistic patient/family expectations about survival, unwillingness to plan end-of-life care, concerns about abandonment or inappropriate care after enrollment in a palliative care program, and family disagreements about care goals. For institutional/program/allocation system barriers, only the requirement for weight loss or gain to meet program-specific BMI requirements was identified. Significant physician barriers included competing time demands and the seemingly contradictory goals of transplant vs palliative care. Strategies recommended to improve palliative care included routine advance care planning for patients awaiting transplantation, access to palliative care specialists, training of transplant physicians in symptom management, and regular meetings among transplant physicians, nurses, patients, and families. Conclusions Physicians providing care to lung transplant candidates reported considerable barriers to the delivery and acceptance of palliative care and identified specific strategies to improve palliative care for lung transplant candidates.

Lung transplantation (LTx) is an established therapy for patients with end-stage cystic fibrosis (CF). Indeed, CF is the commonest indication for those aged

Objectives As life expectancy for women with cystic fibrosis (CF) improves, reproductive decision-making is becoming increasingly relevant. We sought to characterize fertility intentions, contraceptive use, and preferences among adult females with CF. Study design We conducted a cross-sectional survey of contraceptive use and preferences in reproductive-aged women with CF. Subjects were recruited via an electronic mailing list from the Penn Adult Cystic Fibrosis Program. Results Fifty-three women with CF responded and met eligibility criteria. Most (83%) were sexually active, however only 49% used contraception. Condoms and the oral contraceptive pill were the most commonly used methods. Compared to the national contraceptive use among Caucasian women (65%), use in our cohort was significantly lower (p = 0.01). Participants prioritized effectiveness and ease of use in their contraceptive method; they wanted to avoid side effects and interference with sexual enjoyment. Although these priorities are similar to Caucasian women in the literature, additional contraceptive priorities differed significantly between the groups. Conclusions This CF cohort is sexually active but contraceptive utilization was low, and women with CF identify specific contraceptive preferences. There is a significant unmet need for contraception among women with CF.

Background Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation. The risk of developing PTLD varies depending on a number of factors, including the organ transplanted and the degree of immunosuppression used. Methods We report a retrospective analysis of 35 patients with PTLD treated at our center after lung transplantation. Of 705 patients who received allografts, 34 (4.8%) developed PTLD. One patient underwent transplantation elsewhere and was treated at our center. Results PTLD involved the allograft in 49% of our patients and the gastrointestinal (GI) tract lumen in 23%. Histologically, 39% of tumors were monomorphic and 48% polymorphic. The time to presentation defined the location and histology of disease. Of 17 patients diagnosed within 11 months of transplantation, PTLD involved the allograft in 12 (71%) and the GI tract in 1 ( p = 0.01). This "early" PTLD was 85% polymorphic ( p = 0.006). Conversely, of the 18 patients diagnosed more than 11 months after transplant, the lung was involved in 5 (28%) and the GI tract in 7 (39%; p = 0.01). "Late" PTLD was 71% monomorphic ( p = 0.006). Median overall survival after diagnosis was 18.57 months. Overall survival did not differ between all lung transplant recipients and those who developed PTLD. Conclusions PTLD is an uncommon complication after lung transplantation, and its incidence declined remarkably in the era of modern immunosuppression. We report several factors that are important for predisposition toward, progression of, and treatment of PTLD after lung transplantation.

This study tested the discriminant validity of International Society for Heart and Lung Transplantation (ISHLT) primary graft dysfunction (PGD) grades with lung injury biomarker profiles and survival.The study samples consisted of a multicenter prospective cohort study for the biomarker analysis and a cohort study of 450 patients for the mortality analyses. PGD was defined according to ISHLT consensus at 24, 48, and 72 hours after transplantation. We compared the changes in plasma markers of acute lung injury between PGD grades using longitudinal data models. To test predictive validity, we compared differences in the 30-day mortality and long-term survival according to PGD grade.PGD Grade 3 demonstrated greater differences between plasma intercellular adhesion molecule 1 (ICAM-1), protein C, and plasminogen activator inhibitor type 1 (PAI-1) levels than did PGD Grades 0 to 2 at 24, 48, and 72 hours after lung transplantation (p0.05 for each). Grade 3 had the highest 30-day (test for trend p0.001) and overall mortality (log rank p0.001), with PGD Grades 1 and 2 demonstrating intermediate risks of mortality. The ability to discriminate both 30-day and overall mortality improved as the time of grading moved away from the time of transplantation (test for trend p0.001).The ISHLT grading system has good discriminant validity, based on plasma markers of lung injury and mortality. Grade 3 PGD was associated with the most severely altered plasma biomarker profile and the worst outcomes, regardless of the time point of grading. PGD grade at 48 and 72 hours discriminated mortality better than PGD grade at 24 hours.

The effects of lung transplant recipient race on post-transplant outcomes have not been adequately evaluated. This cohort study seeks to determine the characteristics of African American lung transplant recipients and the effects of African American race on post-transplant outcomes, particularly acute and chronic rejection, compared with white recipients, at a single center.There were 485 first-time lung transplantations (431 white, 47 African American, 5 Hispanic and 2 Asian recipients) performed at the University of Pennsylvania between 1991 and 2006. All white and African American recipients were compared based on pre-transplant diagnoses and post-transplant survival. The cohort from 1998 to 2006 (239 white and 25 African American recipients) was also compared based on acute rejection score (ARS) and development of bronchiolitis obliterans syndrome (BOS).Chronic obstructive pulmonary disease was the most common diagnosis leading to lung transplantation in both groups, but sarcoidosis was a much more common indication in African American recipients (white, 1%; African American, 28%; p0.001). Survival was similar in the two groups (white vs African American groups: 1 month, 90.0% vs 87.2%; 1 year, 74.9% vs 74.5%; 5 years, 52.3% vs 50.5%, respectively; p = 0.84). Freedom from BOS at 3 years (white, 60.3%; African American, 62.8%; p = 0.30) and ARS per biopsy (white, 0.83 +/- 0.82; African American, 0.63 +/- 0.77; p = 0.31) were similar in both groups.White and African American patients seek lung transplantation for different diseases, but post-transplant outcomes were found to be similar. Larger, multi-center studies are needed to confirm these results.

This article reviews lung transplantation in patients with cystic fibrosis (CF). Lung transplantation is commonly utilized for patients with end-stage CF. There are several characteristics of CF that present unique challenges before and after lung transplantation. There is new information available that can be utilized to predict outcomes in patients with end-stage CF, and therefore can help in decisions of referral and listing for lung transplantation. The new lung allocation score, which allocates organs to patients who are on the lung transplant waiting list in the United States, presents new challenges and opportunities for patients with end-stage CF. In addition, the effect of the presence of microbiological flora prior to lung transplantation has been better linked to outcomes after lung transplantation. It is now known that, other than those patients harboring Burkholderia cepacia in their lungs before transplantation, most CF patients can undergo transplantation successfully. Nutrition remains an important issue among CF patients, and diabetes is a common problem after lung transplantation. In contrast, liver disease does not usually present major problems but, if it is severe, can necessitate liver and lung transplantation. Mechanical ventilation prior to transplantation might not be an absolute contraindication for CF patients. CF lung transplant recipients have good outcomes after lung transplantation compared with those of other lung transplant recipients. Quality of life is dramatically improved. However, they are still prone to common complications that all lung transplant recipients are prone to, including primary graft dysfunction, acute and chronic rejection, a variety of infections and malignancies, and renal failure.

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Local expertise and waiting list issues are important in influencing the choice of SLT versus BLT. Most of the data support the use of BLT for the majority of COPD patients when available, and the use of SLT for the majority of idiopathic pulmonary fibrosis (IPF) patients. The ultimate choice of operation will depend on donor and recipient characteristics and local expertise and waiting list issues.

The effect of the new lung allocation score on ranking of patients on the waiting list and the number of transplants performed is not known. We assessed this effect on our lung transplant program and conducted a simulation of lung transplants for the first few months of the new system, using the old waiting lists. Patients with idiopathic pulmonary fibrosis had improved rankings and patients with emphysema had worse rankings, but the number of transplants for each disease category did not change significantly compared with the simulated transplants.

Background Aspiration secondary to gastroesophageal reflux has been postulated to be a contributing factor in bronchiolitis obliterans after lung transplantation. It is not clear whether gastroesophageal reflux is a preexisting condition or secondary to intraoperative vagal injury or drug-induced prolonged gastric emptying. Methods The prevalence of gastroesophageal reflux was examined in 78 consecutive end-stage lung disease patients assessed for lung transplantation: emphysema, 21; cystic fibrosis, 5; idiopathic pulmonary fibrosis, 26; scleroderma, 10; and miscellaneous diseases, 16. All underwent esophageal manometry. Two-channel esophageal 24-hour pH testing was completed in 76 patients. Gastric emptying studies were conducted in 36 patients. Results Typical gastroesophageal reflux symptoms were documented in 63% of patients. The lower esophageal sphincter was hypotensive in 72% of patients, and 33% had esophageal body dysmotility. Prolonged gastric emptying was documented in 44%, and 38% had abnormal pH testing. The overall DeMeester score was above normal in 32% of patients, and 20% had abnormal proximal pH probe readings. Conclusions Gastroesophageal reflux is highly prevalent in end-stage lung disease patients who are candidates for lung transplantation. Further investigation is needed to study the prevalence of gastroesophageal reflux after lung transplantation and its contribution to chronic allograft dysfunction.

Background Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS. Materials and methods Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was defined as "early" if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels (≥8 μmol/L). Results Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21 (57%) of 36. Median BALF bile acid values were 1.6 μmol/L (range, 0–32 μmol/L) in BOS patients and 0.3 μmol/L (range, 0–16 μmol/L) in non-BOS patients ( P = .002); 2.6 μmol/L (range, 0–32 μmol/L) in early BOS patients and 0.8 μmol/L (range, 0–4.6 μmol/L) in late BOS patients, ( P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r=0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001). Conclusions Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.

Introduction Lung transplantation is an acceptable treatment option for end-stage lung disease. Short-term survival has improved, but lung transplant recipients remain at high risk for a variety of complications that can necessitate care in an ICU. Little is known about the epidemiology, clinical outcomes, and risk factors for survival among lung transplant recipients admitted to the ICU. Methods All lung transplant recipients at a single institution discharged from the hospital after their transplant and subsequently admitted to the medical ICU (MICU) between March 1, 1999, and February 28, 2001, were included. Patients were followed until death or February 28, 2002. Demographic data collected included transplant type and date, APACHE (acute physiology and chronic health evaluation) III scores, last preadmission and best posttransplant FEV 1 in liters, admitting diagnosis, use of mechanical ventilation, and previous MICU admission. Results There were 51 patients admitted to the MICU during the study period (73 total admissions). Their demographic data, pretransplant diagnoses, and type of transplant were similar to those of the rest of Duke University Medical Center lung transplant patients. Fifty-three percent (27 of 51 patients) required mechanical ventilation during their first MICU admission. Thirty-seven percent (19 of 51 patients) died during their first MICU admission. Fifty-nine percent (16 of 27 patients) receiving mechanical ventilation died. Patients who died had lower FEV 1 to posttransplant best FEV 1 ratio prior to MICU admission, and also had higher APACHE III scores on MICU admission compared to survivors: FEV 1 , 51.3 ± 21.9% (n = 14) vs 75.5 ± 20.4% (n = 30) [p = 0.001]; APACHE III score, 77.7 ± 21.4 (n = 19) vs 60.1 ± 16.5 (n = 32) [p = 0.002]. Survival rates by Kaplan-Meier analysis at 1 year and 2 years after initial MICU admission were 43.1% and 40.9%, respectively. The longest survivor is currently alive 1,087 days after initial MICU admission. Conclusion Admission to the MICU is common in lung transplant recipients. MICU care, including mechanical ventilation, is associated with a poor prognosis in lung transplant recipients, but is appropriate for selected patients with good allograft function.

Objectives: Bronchiolitis obliterans is the greatest limitation to the long-term applicability of lung transplantation. Although alloimmune events are important, nonimmune events, such as gastroesophageal reflux, might contribute to lung injury and the development of bronchiolitis obliterans syndrome. Methods: We retrospectively studied the 396 patients who underwent lung transplantation at the Duke Lung Transplant Program from April 1992 to April 2002. Reflux was assessed for using an ambulatory 24-hour esophageal pH probe. Results: Reflux assessment with an esophageal pH probe was obtained in 128 patients after lung transplantation. Abnormal pH study results were present in 93 (73%) patients. Forty-three patients underwent a surgical fundoplication. There was no in-hospital or 30-day mortality in the patients undergoing fundoplication. At the time of fundoplication, 26 patients met the criteria for bronchiolitis obliterans syndrome. After fundoplication, 16 patients had improved bronchiolitis obliterans syndrome scores, with 13 of these patients no longer meeting the criteria for bronchiolitis obliterans syndrome. In patients at least 6 months after lung transplantation and 6 months after fundoplication, the forced expiratory volume in 1 second improved by an average of 24% (mean forced expiratory volume in 1 second before fundoplication, 1.87 L; mean forced expiratory volume in 1 second after fundoplication, 2.19 L/sec; P

Study objectives Lung transplantation continues to be limited by the development of chronic allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS). The effect of a transplant operation on patients with BOS has not been well-studied, but patients who undergo double-lung transplantation have better long-term survival. We hypothesized that double-lung transplantation leads to decreased rates of BOS. Methods A retrospective review of all lung transplant recipients at our institution, surviving for > 6 months after undergoing their transplant operation. Demographic data, information on other factors leading to the development of BOS, survival information, and data on the presence and timing of BOS were collected. Results BOS occurred in 41.3% of the recipients (93 of 225 patients) at a median time of 4.2 years. Single-lung transplantation was associated with increased rates of BOS compared to double-lung transplantation (49.3% vs 31.7%, respectively; p = 0.007), at the time of the analysis. Single-lung and double-lung transplant recipients had different baseline characteristics, but after controlling for these factors the type of transplant remained a significant predictor of the length of time to the onset of BOS in a multivariable proportional hazard model. Conclusions Double-lung transplantation is associated with a reduced risk for BOS in our study population. A multicenter study with complete BOS information on all patients with a single pretransplant diagnosis would be useful to confirm the above findings. Further research is needed to determine how the type of transplant contributes to the risk for BOS.

Background Lung transplantation has become an acceptable treatment option for many end-stage lung diseases. Pulmonary mycetomas are found in patients with end-stage lung diseases, especially sarcoidosis. The clinical course and long-term outcome of these patients after transplantation remains unknown. Methods We reviewed retrospectively the pathology reports of the explanted lungs from all lung and heart-lung transplantations performed at our institution between January 20, 1992, and June 26, 2000. Patients were included in our study if mycetomas were present on the specimens. Information on transplant date and type, diagnosis, information on antifungal therapy and fungal infections pretransplant and posttransplant, and clinical course after transplantation was recorded. Results Mycetomas were present in 3.0% of transplant recipients (9 of 303 patients). The underlying pulmonary diagnoses were sarcoidosis (six patients), and emphysema, idiopathic pulmonary fibrosis, and pneumoconiosis (one patient each). Seven patients received bilateral lung transplants, one patient received a heart/lung transplant, and one patient received a single lung transplant. Aspergillus was isolated from culture in five patients pretransplant and from five patients posttransplant. Six patients received treatment with itraconazole, or IV or inhaled amphotericin B prior to transplantation. All patients who survived transplantation received posttransplant antifungal therapy. Four patients died in the first month after transplantation. Two patients died at 17 months and 24 months posttransplant, respectively; one patient received a second transplant 30 months later; and two patients are alive and free from fungal infections 17 months and 18 months, respectively, after transplantation. All of the medium-term survivors received lengthy therapy with inhaled and systemic amphotericin B and itraconazole before and after transplantation. Conclusions Lung transplant recipients with mycetomas have significantly reduced posttransplant survival. Careful selection of patients and aggressive antifungal therapies before and after transplantation have led to improved outcomes in patients with mycetomas. Additional research is needed to define the best therapeutic strategy for these patients during transplantation.

Background Vitamin D deficiency is common in CF. Whether vitamin D affects pulmonary function in CF is unknown. Methods Data were abstracted from clinically stable CF patients who had pulmonary function studies and serum 25-hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2months of each other. Findings were adjusted for multiple variables known to affect pulmonary function in CF. Results Enrollees totaled 597. Overall mean 25(OH)D level was 29.6±12.8ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1s (FEV 1 ) % predicted ( r =0.20, p r =0.13, p=0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV 1 % predicted even after controlling for multiple other factors known to affect CF lung function. Conclusions Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.

Despite advances in medical care, patients with cystic fibrosis still face limited life expectancy. The most common cause of death remains respiratory failure. End-stage cystic fibrosis can be treated with lung transplantation and is the third most common reason for which the procedure is performed. Outcomes for cystic fibrosis are better than most other lung diseases, but remain limited (5-year survival 60%). For patients with advanced disease lung transplantation appears to improve survival. Outcomes for patients with Burkholderia cepacia remain poor, although they are better for patients with certain genomovars. Controversy exists about Mycobacterium abscessus infection and appropriateness for transplant. More information is also becoming available for comorbidities, including diabetes and pulmonary hypertension among others. Extra-corporeal membrane oxygenation is used more frequently for end-stage disease as a bridge to lung transplantation and will likely be used more in the future.