Introduction Cystic fibrosis (CF) is a life-limiting genetic disorder estimated to affect more than 160 000 individuals and their families worldwide. People living with CF commonly experience significant physical and emotional symptom burdens, disruptions to social roles and complex treatment decision making. While palliative care (PC) interventions have been shown to relieve many such burdens in other serious illnesses, no rigorous evidence exists for palliative care in CF. Thus, this study aims to compare the effect of specialist palliative care plus usual CF care vs usual CF care alone on patient quality of life. Methods and analysis This is a five-site, two-arm, partially masked, randomised superiority clinical trial. 264 adults with CF will be randomly assigned to usual CF care or usual CF care plus a longitudinal palliative care intervention delivered by a palliative care specialist. The trial's primary outcome is patient quality of life (measured with the Functional Assessment of Chronic Illness Therapy-Palliative care instrument). Secondary outcomes include symptom burden, satisfaction with care and healthcare utilisation. Outcomes will be measured at 12 months (primary endpoint) and 15 months (secondary endpoint). In addition, we will conduct qualitative interviews with patient participants, caregivers, and palliative care and CF care team members to explore perceptions of the intervention's impact and barriers and facilitators to dissemination. Ethics and dissemination Human subjects research ethics approval was obtained from all participating sites, and all study participants gave informed consent. We will publish the results of this trial in a peer-reviewed journal. Trial registration number ISRCTN53323164.

Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. Objectives: PROMISE is a postapproval study to understand the broad effects of ETI through 30 months' clinical use in a more diverse U.S. patient population with planned analyses after 6 months. Methods: Prospective, observational study in 487 people with CF age 12 years or older with at least one F508del allele starting ETI for the first time. Assessments occurred before and 1, 3, and 6 months into ETI therapy. Outcomes included change in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI), and self-reported respiratory symptoms. Measurements and Main Results: Average age was 25.1 years, and 44.1% entered the study using tezacaftor/ivacaftor or lumacaftor/ivacaftor, whereas 6.7% were using ivacaftor, consistent with F508del homozygosity and G551D allele, respectively. At 6 months into ETI therapy, ppFEV1 improved 9.76 percentage points (95% confidence interval [CI], 8.76 to 10.76) from baseline, cystic fibrosis questionnaire-revised respiratory domain score improved 20.4 points (95% CI, 18.3 to 22.5), and sweat chloride decreased -41.7 mmol/L (95% CI, -43.8 to -39.6). BMI also significantly increased. Changes were larger in those naive to modulators but substantial in all groups, including those treated with ivacaftor at baseline. Conclusions: ETI by clinical prescription provided large improvements in lung function, respiratory symptoms, and BMI in a diverse population naive to modulator drug therapy, using existing two-drug combinations, or using ivacaftor alone. Each group also experienced significant reductions in sweat chloride concentration, which correlated with improved ppFEV1 in the overall study population. Clinical trial registered with www.clinicaltrials.gov (NCT NCT04038047).

Cystic fibrosis-related diabetes (CFRD) is associated with reduced life expectancy in adults with cystic fibrosis (CF). Voice analysis may be a convenient method for diagnosing and monitoring CFRD. This study aims to determine the relationship between voice characteristics and markers of glucose and glycemic control and to identify if voice analysis can predict high blood glucose levels and glycemic control in adults with CFRD. We conducted a prospective cross-sectional study in adults with CF from March to December 2021. We recorded 3-second voice samples of a sustained /a/ vowel and analyzed voice characteristic using the Computerized Speech Lab with the Multi-Dimensional Voice Program. In female participants with CFRD, the noise-to-harmonic ratio was significantly lower in those with HbA1c ≥ 7. Furthermore, fundamental frequency variation was significantly lower in both male and female participants with CFRD who had a glucose level of 200 mg/dL or higher at the time of collection. This finding was also associated with a high level of point-of-care glucose. The human voice has potential as a non-invasive tool for measuring glucose levels and glycemic control status in CFRD patients in the future.

Background: Patients with cystic fibrosis (CF) are at risk for CF-related bone disease. Women with CF may use estrogen supplementation for reasons other than skeletal health. It is unknown whether estrogen therapy has a beneficial impact on skeletal health in women with CF. Methods: In this retrospective cohort study of women with CF followed at a single CF center, the lumbar spine bone mineral density (BMD) of women with CF exposed to supplemental and not exposed to supplemental estrogen were compared. Spline function models included the main effect of estrogen exposure and the interaction between age and estrogen supplementation. Results: Of the 145 subjects analyzed, 44 subjects were exposed to supplemental estrogen. The baseline characteristics of estrogen exposed and unexposed subjects were similar except for use of CF transmembrane conductance regulator modulators and anti-osteoporosis medications. Women exposed to estrogen reached peak BMD around 21 years of age, but women not exposed to estrogen reached peak BMD around 25 years of age. A significant interaction of age and estrogen supplementation indicated that the lumbar spine BMD trajectories differed by exposure group. Conclusions: Our study demonstrates that few women with CF of reproductive age are prescribed estrogen therapy. Furthermore, estrogen exposure up to age 21 is associated with improved BMD, but estrogen exposure after age 21 does not appear to be associated with improved BMD. Further studies are needed to understand the reasons for the low rates of estrogen use in young women with CF and the optimal timing, dose and formulation of estrogen prescription.

Extensive research has demonstrated disparities in health outcomes and survival between non-Hispanic Caucasian (NHC) and non-Caucasian or Hispanic (minority) persons with cystic fibrosis (CF) in the United States (US). However, very little research has been done to explore the disease experiences of racial and ethnic minority persons with CF. Adult subjects with CF were approached for study participation and to characterize their experiential disease perceptions. Survey data were analyzed using Chi-Square tests and Mann-Whitney U-test for basic categorical and continuous variables, and Kruskal-Wallis one-way ANOVA using ranks for Likert scales. Minority persons reported significantly lower scores (more negative experience) when comparing themselves to others with CF (15.18 ± 2.89 vs 18.40 ± 3.18, P <.01), particularly in the areas of representation in research, experience, and support. We were able to identify the unique experiences of minority persons with CF, including perceived lower disease understanding and poorer representation compared to most others with CF. Further large studies are needed to develop and assess interventions that may be useful for serving these diverse populations.

The association of estrogen supplementation use and quality of life in women with cystic fibrosis (CF) is not well characterized. In this cross-sectional study, women with CF completed quality of life questionnaires during a routine CF clinic visit. The use of estrogen supplementation was associated with higher quality of life scores in all domains of the CF questionnaire-revised (CFQ-R) and was significant in the role limitations and respiratory domains. Most participants who were not currently using estrogen supplementation had previously used estrogen supplementation. Most participants had used estrogen to regulate menses, prevent pregnancy and control symptoms around menses. Use of estrogen supplementation was not associated with differences in life-space mobility or screening for sexual dysfunction. This is the largest study to date investigating the association of estrogen supplementation and quality of life in women with CF. Prospective randomized studies are needed to clarify the association of estrogen supplementation and quality of life in women with CF.

Many patients with cystic fibrosis (CF) are living well into their adult years and contemplating parenthood. Previous studies have shown that there is an opportunity to improve understanding of inheritance and genetics among individuals with CF. This study explored whether a genetic counselling intervention would be associated with a change in knowledge and/or beliefs about genetics and family-building options. Adults (age ≥ 18 years) presenting to a CF clinic were approached for inclusion. Participants completed a pre-intervention survey to measure their knowledge of CF genetics, as well as perceptions and understanding of assisted reproductive technology treatments and other family-building options. Subjects then partook in a genetic counselling session. Subjects repeated the survey immediately after the session and 1–3 months later. Data analysis used one-way analysis of variance (ANOVA), repeated measures ANOVA and multiple linear regression. Thirty-five subjects [19 (54%) men and 16 (45%) women] with a mean (±standard deviation) age of 28 ± 5.64 years were enrolled in the study. Before the intervention, 61.69% ± 4.50 of knowledge-based questions were answered correctly. Immediately after the intervention, the mean score increased to 77.71% ± 3.23, but this decreased to 69.48% ± 4.02 for the third test (P < 0.05, repeated measures ANOVA). Six individuals changed their family-building preference following the genetic counselling session. A short genetic consultation was associated with a significant improvement in CF-specific genetic knowledge. However, knowledge was not retained fully for a longer time period following the consultation. Multiple discussions regarding fertility options are needed to reinforce the key concepts related to CF genetics and fertility.

Primary cells isolated from the human respiratory tract are the state-of-the-art for in vitro airway epithelial cell research. Airway cell isolates require media that support expansion of cells in a basal state to maintain the capacity for differentiation as well as proper cellular function. By contrast, airway cell differentiation at an air–liquid interface (ALI) requires a distinct medium formulation that typically contains high levels of glucose. Here, we expanded and differentiated human basal cells isolated from the nasal and conducting airway to a mature mucociliary epithelial cell layer at ALI using a medium formulation containing normal resting glucose levels. Of note, bronchial epithelial cells expanded and differentiated in normal resting glucose medium showed insulin-stimulated glucose uptake which was inhibited by high glucose concentrations. Normal glucose containing ALI also enabled differentiation of nasal and tracheal cells that showed comparable electrophysiological profiles when assessed for cystic fibrosis transmembrane conductance regulator (CFTR) function and that remained responsive for up to 7 weeks in culture. These data demonstrate that normal glucose containing medium supports differentiation of primary nasal and lung epithelial cells at ALI, is well suited for metabolic studies, and avoids pitfalls associated with exposure to high glucose.

Transition from pediatric to adult care for those with chronic illnesses must have special considerations during the COVID-19 pandemic. The SARS-CoV-2 coronavirus has significantly disrupted social, economic, and health care practices globally. Young adults with special health care needs are at increased risk for poor outcomes during this unprecedented time. We have found that heightened anxiety, health care service disruption, and other logistical complications surrounding the new virus may further confound health care transitions. Increased communication and collaboration with young adults is necessary to provide patient-centered care and ensure they successfully cross the transition chasm.

Active malignancy diagnosed within 5 years is an absolute contraindication for lung transplantation. In this study, we evaluated the rate of incidental malignancies detected in explanted lungs at our institution and assessed the posttransplant survival in patients with nonsmall cell lung cancer (NSCLC). Methods: A retrospective chart review of lung transplant recipients at our institution from February 1999 to June 2017 was conducted. A literature review was performed to evaluate the prevalence and survival outcomes in patients with unexpected malignancies. Results: From 407 patients who underwent lung transplantation, 9 (2.2%) were discovered to have malignant neoplasms. There were 3 cases of adenocarcinoma, 3 cases of adenocarcinoma in situ, 2 cases of squamous cell carcinoma, and 1 case of metastatic renal cell carcinoma. An extensive literature review found 12 case reports or case series reporting malignancy discovered at the time of lung transplantation. The overall prevalence of incidental neoplasms among 6746 recipients is around 1.5% (n = 103). The most common neoplasms discovered included adenocarcinoma (n = 56, 54%) and squamous cell carcinoma (n = 29, 28%). The overall 3-year survival was 54.4% for patients with localized NSCLC compared to 5.7% for those with nonlocalized disease. Conclusions: Unidentified malignancies occur despite aggressive radiographic surveillance with poor posttransplant outcomes in patients with advanced malignancy. Malignancy-related radiographic findings may be missed pretransplant secondary to architectural distortion of lung parenchyma related to end-stage lung disease or because of the critical timing of surgery when donor lungs are available.