Lung function decline is mitigated following liver transplantation in people with cystic fibrosis: A retrospective cohort study.

There is paucity of literature on the health outcomes following liver transplantation (LT) in people with cystic fibrosis (pwCF). We aim to evaluate changes in lung function following LT in pwCF. We performed a retrospective cohort study of pwCF who underwent LT between 1987 and 2019 in the United States and Canada. Simultaneous lung-liver transplants and individuals who had lung transplant prior to LT were excluded. We analyzed pre-LT and post-LT percent predicted forced expiratory volume in 1 second, body mass index, rates of pulmonary exacerbation, and post-LT overall survival. A total of 402 LT recipients were included. The median age of transplant was 14.9 years and 69.7% of the transplants were performed in children less than 18 years old. The rate of decline in percent predicted forced expiratory volume in 1 second was attenuated after LT from -2.2% to -0.7% predicted per year with a difference of 1.5% predicted per year (95% CI, 0.8, 2.2; p < 0.001). Following LT, the rate of decline in body mass index was reduced, and there were fewer pulmonary exacerbations (0.6 pre vs. 0.4 post; rate ratio 0.7, p < 0.01). The median survival time post-transplant was 13.9 years and the overall probability of survival at 5 years was 77.6%. Those with higher lung function pre-LT had a lower risk of death post-LT, and those with genotypes other than F508 deletion had worse survival. LT in pwCF occurs most often in children and adolescents and is associated with a slower rate of decline in lung function and nutritional status, and a reduction in pulmonary exacerbations.

Cystic fibrosis survival outcomes following second lung transplant: The north American experience.

INTRODUCTION: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF). METHODS: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years. RESULTS: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%). CONCLUSIONS: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation.

Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data.

RATIONALE: A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results. OBJECTIVES: To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences. METHODS: We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics). RESULTS: We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK. CONCLUSIONS: Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.

Auto-inflammation and auto-immunity pathways are associated with emergence of BOS in pediatric lung transplantation.

BACKGROUND: Long-term survival after lung transplantation (LTx) is limited by chronic lung allograft dysfunction (CLAD). METHODS: We report an analysis of cytokine profiles in bronchoalveolar lavage samples collected during a prospective multicenter non-interventional trial primarily designed to determine the impact of community-acquired respiratory viral infections (CARV) in outcomes after pediatric LTx. In this analysis, we identify potential biomarkers of auto-inflammation and auto-immunity associated with survival and risk of bronchiolitis obliterans (BOS) after LTx with cytokine analysis of bronchoalveolar lavage fluid (BALF) from 61 pediatric recipients. RESULTS: Higher IL-23 (p = .048) and IL-31 (p = .035) levels were associated with the risk of BOS, and lower levels of epithelial growth factor (EGF) (p = .041) and eotaxin (EOX) (p = .017) were associated with BOS. Analysis using conditional inference trees to evaluate cytokines at each visit associated with survival identified soluble CD30 (p < .001), pro-inflammatory cytokine IL-23 (p = .02), and sTNFRI (p = .01) below cutoff levels as associated with BOS-free survival. CONCLUSIONS: Our results indicate that post-LTx survival in children may be linked to activation of alternate pathways of the immune system that affect airway remodeling in addition to activation of "classical" pathways that have been described in adult LTx recipients. These may indicate pathways to target for intervention.

Pretransplant Quality of Life and Post-Transplant Survival in Adolescents with Cystic Fibrosis.

OBJECTIVE: Cystic fibrosis (CF) is the most common indication for pediatric lung transplantation and the third most common for adults. The selection of candidates and timing of transplant is challenging and whether there is a survival benefit of this procedure for pediatric patients is controversial. Use of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a well-validated, disease-specific quality of life measure may improve pretransplant referral decision-making. METHODS: This multicenter study evaluated whether specific domains on the CFQ-R (i.e., Physical Functioning, Respiratory Symptoms), assessed pretransplant, predicted survival 4-year post-transplant (n = 25). A two-step Cox regression, with physical predictors entered in step one (i.e., age, CF-related Diabetes, FEV1% predicted) and the Physical Functioning and Respiratory Symptoms CFQ-R scales entered in step two, was used to assess whether the CFQ-R explained additional and unique variance. Receiver Operating Characteristic (ROC) curves were used to assess the sensitivity and specificity of optimal cut-points of significant CFQ-R domains. RESULTS: The Respiratory Symptoms scale predicted survival 4-year post-transplant (Exp(B) = 0.38, 95% CI = 0.14-1.01; area under the curve = 0.87) and once it was added to the model, no other individual predictors were significant. The incremental improvement beyond the physical parameters approached but did not reach statistical significance (χ2 Δ = 5.79, p = .06). CONCLUSIONS: This study suggested that including patient-reported outcomes could aid pretransplant referral decision-making. The Respiratory Symptoms scale in particular may serve as a useful tool to help determine when to refer and evaluate an individual for transplant.

Incorporating patient and caregiver feedback into lung transplant referral guidelines for individuals with cystic fibrosis-Preliminary findings from a novel paradigm.

BACKGROUND: Lung transplantation is a common therapeutic option for individuals with cystic fibrosis (CF) and advanced lung disease, yet many individuals with CF are not appropriately referred for evaluation. The present study sought to enhance CF transplant referral guidelines by integrating patient-centered input to identify possible psychosocial barriers contributing to suboptimal referral for appropriate CF transplant candidates. METHODS: As a component of developing the Cystic Fibrosis Foundation (CFF) Lung Transplant Referral Consensus Guidelines, we convened a focus group of lung transplant recipients with CF and two spouses of CF recipients. Each session involved standardized approaches to elicit qualitative, thematic content. RESULTS: CF patients and caregivers characterized five areas for improvement, which were integrated into formal CFF referral guidelines. These included (a) timing of transplant discussion with CF providers, (b) accuracy of transplant-related knowledge and expectations, (c) stigma associated with the need for transplantation, (d) treatment team transition issues, and (e) social support and mental health concerns. Earlier introduction of transplant, greater details regarding manageable aspects of treatment, and greater provision of social support were all associated with better psychosocial experiences. CONCLUSIONS: Integrating patient-centered input into guideline development yielded important and previously unknown psychosocial barriers contributing to suboptimal transplant referral.

Epidemiology and persistence of rhinovirus in pediatric lung transplantation.

BACKGROUND: Infection with rhinovirus (HRV) occurs following pediatric lung transplantation. Prospective studies documenting frequencies, persistence, and progression of HRV in this at-risk population are lacking. METHODS: In the Clinical Trials in Organ Transplant in Children prospective observational study, we followed 61 lung transplant recipients for 2 years. We quantified molecular subtypes of HRV in serially collected nasopharyngeal (NP) and bronchoalveolar lavage (BAL) samples and correlated them with clinical characteristics. RESULTS: We identified 135 community-acquired respiratory infections (CARV) from 397 BAL and 480 NP samples. We detected 93 HRV events in 42 (68.8%) patients, 22 of which (23.4%) were symptomatic. HRV events were contiguous with different genotypes identified in 23 cases, but symptoms were not preferentially associated with any particular species. Nine (9.7%) HRV events persisted over multiple successive samples for a median of 36 days (range 18-408 days). Three persistent HRV were symptomatic. When we serially measured forced expiratory volume in one second (FEV1) in 23 subjects with events, we did not observe significant decreases in lung function over 12 months post-HRV. CONCLUSION: In conjunction with our previous reports, our prospectively collected data indicate that molecularly heterogeneous HRV infections occur commonly following pediatric lung transplantation, but these infections do not negatively impact clinical outcomes.

Effect of Including Important Clinical Variables on Accuracy of the Lung Allocation Score for Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Rationale: Clinical variables associated with shortened survival in patients with advanced-stage cystic fibrosis (CF) are not included in the lung allocation score (LAS).Objectives: To identify variables associated with wait-list and post-transplant mortality for CF lung transplant candidates using a novel database and to analyze the impact of including new CF-specific variables in the LAS system.Methods: A deterministic matching algorithm identified patients from the Scientific Registry of Transplant Recipients and the Cystic Fibrosis Foundation Patient Registry. LAS wait-list and post-transplant survival models were recalculated using CF-specific variables. This multicenter, retrospective, population-based study of all lung transplant wait-list candidates aged 12 years or older from January 1, 2011, to December 31, 2014, included 9,043 patients on the lung transplant waiting list and 6,110 lung transplant recipients between 2011 and 2014, comprising 1,020 and 677 with CF, respectively.Measurements and Main Results: Measured outcomes were changes in LAS and lung allocation rank. For CF candidates, any Burkholderia sp. (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.2-6.6), 29-42 days hospitalized (HR 2.8; CI 1.3-5.9), massive hemoptysis (HR 2.1; CI 1.1-3.9), and relative drop in FEV1 ≥30% over 12 months (HR 1.7; CI 1.0-2.8) increased wait-list mortality risk; pulmonary exacerbation time 15-28 days (1.8; 1.1-2.9) increased post-transplant mortality risk. A relative drop in FEV1 ≥10% in chronic obstructive pulmonary disease (COPD) candidates was associated with increased wait-list mortality risk (HR 2.6; CI 1.2-5.4). Variability in LAS score and rank increased in patients with CF. Priority for transplant increased for COPD candidates. Access did not change for other diagnosis groups.Conclusions: Adding CF-specific variables improved discrimination among wait-listed CF candidates and benefited COPD candidates.

Absence of evidence that respiratory viral infections influence pediatric lung transplantation outcomes: Results of the CTOTC-03 study.

Based on reports in adult lung transplant recipients, we hypothesized that community-acquired respiratory viral infections (CARVs) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome/obliterative bronchiolitis, retransplant, or death. Blood, bronchoalveolar lavage, and nasopharyngeal specimens were obtained with standard of care visits. Nasopharyngeal specimens were obtained from recipients with respiratory viral symptoms. Respiratory specimens were interrogated for respiratory viruses by using multiplex polymerase chain reaction. Donor-specific HLA antibodies, self-antigens, and ELISPOT reactivity were also evaluated. Survival was 84% (1 year) and 68% (3 years). Bronchiolitis obliterans syndrome incidence was 20% (1 year) and 38% (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (hazard ratio 0.64 [95% confidence interval: 0.25-1.59], P = .335) or between CARV and the development of alloimmune or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that observed in adults.

Clinical characteristics of cystic fibrosis patients prior to lung transplantation: An international comparison between Canada and the United States.

BACKGROUND: Cystic fibrosis (CF) patients from Canada have better-reported post-lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. METHODS: Population-based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. RESULTS: Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). CONCLUSIONS: CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post-transplant survival.

Anellovirus loads are associated with outcomes in pediatric lung transplantation.

Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as "composite" (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism.

OBJECTIVE: To compare outcomes of infants and children who underwent lung transplantation for genetic disorders of surfactant metabolism (SFTPB, SFTPC, ABCA3, and NKX2-1) over 2 epochs (1993-2003 and 2004-2015) at St Louis Children's Hospital. STUDY DESIGN: We retrospectively reviewed clinical characteristics, mortality, and short- and long-term morbidities of infants (transplanted at <1 year; n = 28) and children (transplanted >1 year; n = 16) and compared outcomes by age at transplantation (infants vs children) and by epoch of transplantation. RESULTS: Infants underwent transplantation more frequently for surfactant protein-B deficiency, whereas children underwent transplantation more frequently for SFTPC mutations. Both infants and children underwent transplantation for ABCA3 deficiency. Compared with children, infants experienced shorter times from listing to transplantation (P = .014), were more likely to be mechanically ventilated at the time of transplantation (P < .0001), were less likely to develop bronchiolitis obliterans post-transplantation (P = .021), and were more likely to have speech and motor delays (P ≤ .0001). Despite advances in genetic diagnosis, immunosuppressive therapies, and supportive respiratory and nutritional therapies, mortality did not differ between infants and children (P = .076) or between epochs. Kaplan-Meier analyses demonstrated that children transplanted in epoch 1 (1993-2003) were more likely to develop systemic hypertension (P = .049) and less likely to develop post-transplantation lymphoproliferative disorder compared with children transplanted in epoch 2 (2004-2015) (P = .051). CONCLUSION: Post-lung transplantation morbidities and mortality remain substantial for infants and children with genetic disorders of surfactant metabolism.

Risk and outcomes of pulmonary fungal infection after pediatric lung transplantation.

BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes. RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48). CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study.

Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study.

Prediction of PTLD after pediatric lung transplant remains difficult. Use of EBV VL in WB has been poorly predictive, while measurement of VL in BAL fluid has been suggested to have enhanced utility. The NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC-03) prospectively obtained serial quantitative measurements of EBV PCR in both WB and BAL fluid after pediatric lung transplantation. Descriptive statistics, contingency analyses, and Kaplan-Meier analyses evaluated possible association between EBV and PTLD. Of 61 patients, 34 (56%) had an EBV+PCR (at least once in WB or BAL). EBV donor (D)+patients more often had a positive PCR (D+/recipient (R)-: 13/18; D+/R+: 14/23) compared to EBV D- patients (6/17). Several D-/R- (5/12) patients developed EBV, but none developed PTLD. All four PTLD patients were D+/R- with EBV+PCR. Neither the time to first EBV+PCR nor the CT for PCR positivity in BAL or WB was statistically different between those with and without PTLD. Having an EBV-seropositive donor was associated with increased risk of EBV+PCR in WB. EBV load in BAL was not predictive of PTLD.

Official American Thoracic Society technical standards: flexible airway endoscopy in children.

BACKGROUND: Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published technical standards on how to perform FAE in children are lacking. METHODS: The American Thoracic Society (ATS) approved the formation of a multidisciplinary committee to delineate technical standards for performing FAE in children. The committee completed a pragmatic synthesis of the evidence and used the evidence synthesis to answer clinically relevant questions. RESULTS: There is a paucity of randomized controlled trials in pediatric FAE. The committee developed recommendations based predominantly on the collective clinical experience of our committee members highlighting the importance of FAE-specific airway management techniques and anesthesia, establishing suggested competencies for the bronchoscopist in training, and defining areas deserving further investigation. CONCLUSIONS: These ATS-sponsored technical standards describe the equipment, personnel, competencies, and special procedures associated with FAE in children.

FEV1 Variability Predicts Lung Transplant or Mortality in Cystic Fibrosis Patients in the US.

RATIONALE: Declines in percent predicted Forced Expiratory Volume in 1 Second (ppFEV1) are an important marker of clinical progression of Cystic Fibrosis (CF). OBJECTIVES: We examined ppFEV1 variability on a combined outcome of lung transplant or death. METHODS: We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children ages 8 years and above with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a two-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated based upon quartiles of the cumulative distribution of ppFEV1 variability. MEASUREMENTS AND MAIN RESULTS: We included 9,706 CF patients in our cohort. Median age at cohort entry was 8.3 (IQR 8.2 - 8.4) years, 50% of patients were female, 94% white, and median baseline ppFEV1 was 94.4 (IQR 81.6 - 106.1). The unadjusted HR for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% CI 3.48 - 4.90) and the weighted HR was 1.49 (95% CI 1.19 - 1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1 variability increased. CONCLUSIONS: We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the US.

Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Prevalence of unmet pain and symptom management needs in adults with cystic fibrosis.

BACKGROUND: Although people living with CF (PLwCF) commonly report pain and other symptoms, little is known regarding their experiences of living with and accessing treatment for burdensome symptoms. METHODS: PLwCF completed online questionnaires assessing symptom prevalence and distress and were also asked about experiences accessing pain and symptom treatment, using both closed-ended and free-text entries. RESULTS: Pain was the most prevalent symptom experienced among the 55 participants (76%) and the symptom that most commonly caused distress (64%). PLwCF not on CFTR modulator therapy were likelier to endorse pain as distressing (p = 0.007). Respondents expressed that their pain was commonly underrecognized and undermanaged, they desired a multi-modal approach to treatment, and noted concerns about disease progression affecting their symptom management options. CONCLUSIONS: Our study suggests that PLwCF often have unmet symptom management needs that may impair quality of life.

Clinician perspectives on barriers and solutions to symptom management in cystic fibrosis.

People living with cystic fibrosis (PLwCF) experience high symptom burden. 146 clinicians completed online surveys regarding barriers and solutions to symptom management between September and October 2020. The surveys contained both closed-ended and free-text entries. The symptom management specialists that CF clinicians most wished to consult included mental health (88, 65%), palliative care (59, 41%), and pain specialists (48, 33%). Barriers to symptom management included concerns about controlled substances prescribed for symptom control causing addiction and precluding transplantation, a lack of trust and collaboration among clinical specialties, a lack of symptom management specialists with CF expertise, and a worry about the affordability of specialist-level symptom management care. Potential solutions included non-pharmacological approaches, expanding access to affordable specialist symptom management care, the creation of clinical care guidelines for symptom management in CF, and having CF clinicians and symptom management specialists work alongside each other in CF clinic to build interdisciplinary trust and education.