Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.

BACKGROUND: Levels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF. METHODS: We compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1). We also evaluated DHEA-S levels in people with CF on elexacaftor-tezacaftor-ivacaftor (ETI) (n = 145). RESULTS: PwCF (not on ETI) had lower DHEA-S levels compared to healthy non-CF controls. DHEA-S levels in individuals with CF on ETI were similar to those without CF. Lower DHEA-S levels were associated with lower ppFEV1. CONCLUSIONS: PwCF (not on ETI) have lower levels of DHEA-S than people without CF or people with CF on ETI. Additional studies are needed to investigate the impact of DHEA-S on the health of pwCF and mechanisms involved.

Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

BACKGROUND: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning. METHODS: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care. During the workshop, we used results and reviewed existing research to establish research priorities and design studies to address identified knowledge gaps. RESULTS: A total of 303 respondents (85 % PwCF, 15 % caregivers) completed the survey. Highly-rated SRH topics were: 1) effects of CF modulator therapy on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health. Twenty-four workshop participants established the need for further research on sex hormones and CF, optimizing SRH care provision, and fertility/ART. CONCLUSION: SRH is an important and emerging area in CF and thoughtful consideration of community perspectives can ensure that future research is relevant and responsive.

The impact of switching to race-neutral reference equations on FEV1 percent predicted among people with cystic fibrosis.

RATIONALE: The American Thoracic Society recommended switching to race-neutral spirometry reference equations, as race is a social construct and to avoid normalizing disparities in lung function due to structural racism. Understanding the impact of the race-neutral equations on percent predicted forced expiratory volume in one second (ppFEV1) in people with cystic fibrosis (PwCF) will help prepare patients and providers to interpret pulmonary function test results. OBJECTIVE(S): To quantify the impact of switching from Global Lung Initiative (GLI) 2012 race-specific to GLI 2022 Global race-neutral reference equations on the distribution of ppFEV1 among PwCF of different races. METHODS: Cross-sectional analysis of FEV1 among PwCF ages ≥6 years in the 2021 U.S. Cystic Fibrosis Foundation Patient Registry. We describe the absolute difference in ppFEV1 between the two reference equations by reported race and the effect of age and height on this difference. RESULTS: With the switch to GLI Global, ppFEV1 will increase for White (median increase 4.7, (IQR: 3.1; 6.4)) and Asian (2.6 (IQR: 1.6; 3.7)) individuals and decrease for Black individuals (-7.7, (IQR: -10.9; -5.2)). Other race categories will see minimal changes in median ppFEV1. Individuals with higher baseline ppFEV1 and younger age will see a greater change in ppFEV1 (i.e., a greater improvement among White and Asian individuals and a greater decline among Black individuals). CONCLUSIONS: Switching from GLI 2012 race-specific reference equations to GLI 2022 Global race-neutral equations will result in larger reductions in ppFEV1 among Black individuals with CF than increases among White and Asian people with CF.

Sex differences in outcomes of people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: There is a well described sex-disparity in outcomes of individuals with cystic fibrosis (CF), with females faring worse than males. Given the dramatic improvement in overall health of people with CF using CF transmembrane conductance regulator (CFTR) modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), the sex-disparity in CF warrants re-examination. METHODS: We evaluated the effects of ETI use by sex prior to versus after initiation of ETI by pulmonary exacerbations (PEx), percent predicted forced expiratory volume in one second (ppFEV1), presence of Pseudomonas aeruginosa in sputum cultures, and body mass index (BMI). We used univariate and multivariable longitudinal regression adjusting for key confounders, such as age, race, CFTR modulator taken prior to ETI and baseline ppFEV1. RESULTS: We included 251 individuals started on ETI between January 2014 to September 2022. We collected data for a mean of 5.45 years pre-ETI and 2.38 years post-ETI. We found the adjusted presence of PEx decreased more in males than females pre- to post-ETI with the odds of having a PEx in males being 0.57 (43% reduction) versus females 0.75 (25% reduction) (p = 0.049). We found no statistical difference by sex for ppFEV1, presence of Pseudomonas aeruginosa or BMI pre- to post-ETI by sex. CONCLUSION: After treatment with ETI, there was a greater decline in PEx in males versus females. Long-term impact of ETI by sex is still unknown, but we will need to seek ways to effectively tailor care for individuals with CF and consider pharmacokinetic studies of ETI comparing males to females.

A provider survey assessing fetal impact of CFTR modulator use in males with CF during assisted and unassisted reproduction and partner pregnancy.

BACKGROUND: Most males with cystic fibrosis (mwCF) are infertile but with CF transmembrane conductance regulator (CFTR) modulator-conferred benefits, more are utilizing assisted reproductive technologies (ART). Administration of normal human doses of modulators in animal reproductive models caused no genotoxicity; no human data exists. Potential health decline following modulator discontinuation makes the decision to withhold therapy during reproduction challenging. METHODS: From August-October 2021, international CF clinicians completed an anonymous questionnaire regarding mwCF who used modulators during reproduction. RESULTS: We received 42 surveys for mwCF with partner pregnancies. Forty of 42 mwCF utilized ART; 35 continued modulators during sperm retrieval and 40/42 during partner pregnancy. One of four males who discontinued modulators experienced clinical deterioration. First trimester miscarriages occurred in 11.9 % of partner pregnancies. No congenital anomalies were reported. CONCLUSIONS: Use of CFTR modulators during reproduction and partner pregnancy in mwCF did not result in a higher-than-expected miscarriage rate nor congenital anomalies.

Clinician perspectives and practices related to sexual and reproductive care provision for males with cystic fibrosis.

BACKGROUND: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care. METHODS: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care. We compared responses across groups by population served (pediatric vs. adult vs. both pediatric and adult MwCF) using chi square/Fisher's exact tests. RESULTS: A total of 297 clinicians completed the survey (41 % pediatric, 36 % adult, 23 % both; 27 % physicians, 24 % social workers, 11 % nurses, 41 % other). Nearly all (98 %) believed the CF team had a role in SRH care with 75 % believing they should be primarily responsible. Pediatric clinicians were less likely to deem SRH topics important and less likely to report annual discussions compared to adult colleagues (all p<0.05). Pediatric clinicians reported less comfort in their SRH knowledge than adult colleagues (p<0.001) and in their ability to provide SRH care (p<0.05). Common barriers endorsed by respondents included lack of SRH knowledge (75 %) and presence of family/partners in exam room (64 %). A majority rated SRH screening tools (91 %), partnerships with SRH specialists (90 %), clinician training (83 %), and management algorithms (83 %) as potential facilitators. CONCLUSION: Multidisciplinary CF clinicians perceive SRH for MwCF as important but report suboptimal SRH discussions. Pediatric clinicians report significantly less comfort and skill in discussing and managing male SRH. Identified barriers and facilitators should be used to improve SRH care for MwCF.

Factors associated with pubertal growth outcomes in cystic fibrosis: Early Growth and Puberty in CF.

BACKGROUND: Pubertal delays in children with cystic fibrosis (CF) have historically been common. It is unclear to what degree puberty is affected in the new era of CF care or the role of early nutritional status. We hypothesized that more favorable early growth trajectories are associated with improved pubertal growth outcomes. METHODS: We used data from the United States CF Foundation Patient Registry to analyze associations between early weight-for-length/body mass index (WFL-BMI) growth trajectories and pubertal outcomes, using peak height velocity (PHV) and age at PHV (APHV) as proxy measures for puberty in addition to adult height (defined as height at age 18 years). Our analysis consisted of shape invariant mixed modeling and multivariable linear regression. RESULTS: Our sample consisted of 9,186 people with CF aged 18 to 21 years between 2010-2019. APHV was earliest and PHV/adult height were highest in those with WFL-BMI always >50th percentile from 0-6 years. However, there was no difference after adjusting for key covariates. Receiving CF transmembrane conductance regulator (CFTR) modulator therapy in childhood was associated with being taller at 18 years, by 0.92 cm in males (p=0.048) and 1.02 cm in females (p=0.010) in adjusted models. Higher height z-score at 2 years was associated with improved APHV and PHV for males and improved adult height for both males and females (p<0.001) in adjusted models. CONCLUSIONS: Early height, but not early WFL-BMI trajectories, may be associated with pubertal growth outcomes. CFTR modulator therapy shows the potential to improve pubertal growth outcomes, but further research is necessary.

The modern landscape of fertility, pregnancy, and parenthood in people with cystic fibrosis.

PURPOSE OF REVIEW: With improved long-term survival and the expanding availability of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies that treat the underlying genetic defect in cystic fibrosis, more people are interested in parenthood. Cystic fibrosis care centers and people with cystic fibrosis need more information to guide decisions related to parenting. RECENT FINDINGS: Here we present currently available data on fertility, pregnancy, and parenthood in the modern era of cystic fibrosis care. Fertility may be improving in female individuals with cystic fibrosis with the use of CFTR modulator therapies, and there is an associated increase in annual pregnancies. Infertility in male individuals with cystic fibrosis remains approximately 97-98% and is unchanged with CFTR modulators in those already born with cystic fibrosis. As more female individuals with cystic fibrosis experience pregnancy, questions remain about the impact of pregnancy on their health and that of their child. Fortunately, there are multiple routes to becoming a parent; however, more work is needed to understand the impact of pregnancy and parenthood in the context of CF as some previous data suggests potential challenges to the health of parents with cystic fibrosis. SUMMARY: We encourage cystic fibrosis care teams to have knowledge and resources available to support the reproductive goals of all individuals with cystic fibrosis.

Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective.

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics.

Chronic Pancreatitis Associated With a Variant of CFTR Gene Treated With Total Pancreatectomy and Autologous Islet Cell Transplantation.

Background/Objective: Total pancreatectomy is performed for pain relief in chronic pancreatitis. Concomitant autologous islet cell transplantation can be performed to improve glycemic control. We report the case of a patient with chronic pancreatitis who underwent a total pancreatectomy with autologous islet cell transplantation with increasing insulin requirements and its association with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder. Case Report: A 40-year-old woman presented with abdominal pain and had elevated levels of serum lipase. She was treated for acute pancreatitis. In the subsequent 2 years, she had 4 additional episodes of pancreatitis and eventually developed chronic abdominal pain. She underwent total pancreatectomy for pain relief with autologous intrahepatic islet cell transplantation. She experienced repeated episodes of pneumonia and underwent screening for cystic fibrosis, which showed a 7T/7T polymorphic variant at CFTR intron 8. The follow-up at 8 years after procedure showed increasing hemoglobin A1c levels despite increasing insulin use with multiple hospitalizations for hyperglycemia. The patient was transitioned to continuous subcutaneous insulin infusion with improvement in hemoglobin A1c levels. Discussion: Chronic pancreatitis can be a manifestation of an undiagnosed CFTR-related disorder, which in this case was followed by total pancreatectomy. Autologous islet cell transplantation was performed with declining postprocedural glycemic control. Interval failure of the transplanted islets is present in up to two thirds of the patients but is not affected by the presence of cystic fibrosis. Conclusion: A gradual decline in glycemic control may be expected in patients with autologous islet cell transplantation and can be improved with the use of continuous subcutaneous insulin infusion.

Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis.

INTRODUCTION: Following availability of the highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator, elexacaftor/tezacaftor/ivacaftor, there was a near doubling of pregnancies reported in the United States (US) in people with CF. We sought to determine health impacts of planned (PP) versus unplanned pregnancies (UP). METHODS: We collected retrospective pregnancy data from January 2010-December 2020 from 11 US CF centers. After adjusting for potential confounding effects, we conducted multivariable, multilevel longitudinal regression analysis using mixed effect modeling to assess whether changes in percent predicted forced expiratory volume in one second (ppFEV1), body mass index (BMI), and pulmonary exacerbations (PEx) 1-year-pre- to 1-year-post-pregnancy were associated with pregnancy planning. RESULTS: Our analysis included 163 people with 226 pregnancies; the cohort had a mean age at conception of 29.6 years, mean pre-pregnancy ppFEV1 of 75.4 and BMI of 22.5 kg/m2. PpFEV1 declined in both PP (adjusted decline of -2.5 (95% CI: -3.8, -1.2)) and UP (adjusted decline of -3.0 (95% CI: -4.6, -1.4)) groups, they did not differ from each other (p = 0.625). We observed a difference in change in the annual number of PEx pre- to post-pregnancy (PP: 0.8 (0.7, 1.1); UP: 1.3 (1.0, 1.7); interaction effect p = 0.029). In a subset of people with available infant data, infants resulting from UP had more preterm births, lower APGAR scores, and more intensive care unit stays. CONCLUSIONS: Following UP, there is an increased trajectory for PEx and potentially for infant complications compared to PP. Clinicians should consider increased surveillance in the setting of UP.

Immunoreactive Trypsinogen in Infants Born to Women with Cystic Fibrosis Taking Elexacaftor-Tezacaftor-Ivacaftor.

Most people with cystic fibrosis (CF) are diagnosed following abnormal newborn screening (NBS), which begins with measurement of immunoreactive trypsinogen (IRT) values. A case report found low concentrations of IRT in an infant with CF exposed to the CF transmembrane conductance regulator (CFTR) modulator, elexacaftor-tezacaftor-ivacaftor (ETI), in utero. However, IRT values in infants born to mothers taking ETI have not been systematically assessed. We hypothesized that ETI-exposed infants have lower IRT values than newborns with CF, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID), or CF carriers. IRT values were collected from infants born in Indiana between 1 January 2020, and 2 June 2022, with ≥1 CFTR mutation. IRT values were compared to infants born to mothers with CF taking ETI followed at our institution. Compared to infants identified with CF (n = 51), CRMS/CFSPID (n = 21), and CF carriers (n = 489), ETI-exposed infants (n = 19) had lower IRT values (p < 0.001). Infants with normal NBS results for CF had similar median (interquartile range) IRT values, 22.5 (16.8, 30.6) ng/mL, as ETI-exposed infants, 18.9 (15.2, 26.5). IRT values from ETI-exposed infants were lower than for infants with abnormal NBS for CF. We recommend that NBS programs consider performing CFTR variant analysis for all ETI-exposed infants.

The Impact of Highly Effective Cystic Fibrosis Transmembrane Conductance Regulator Modulators on the Health of Female Subjects With Cystic Fibrosis.

Cystic fibrosis (CF) is a genetic disorder that occurs in people of all genetic ancestries. CF is caused by variants in the CF transmembrane conductance regulator (CFTR) gene that result in decreased, absent, or nonfunctional CFTR protein at the cell surface of the mucous membranes. Clinical manifestations include chronic respiratory disease, malabsorption, and decreased fertility. Historically, therapies for CF were focused on the signs and symptoms of the disease. However, more recently, CFTR modulators, therapies directed at the basic defect, are improving the quality and duration of the lives of people with CF. The predicted survival of people with CF in the United States is now 53 years of age. With the hope of longer, healthier lives, female individuals with CF (fwCF) are expressing the desire to discuss fertility, pregnancy, and parenthood. Furthermore, pregnancy rates are increasing substantially. Understanding the impact of use or discontinuation of highly effective modulator therapy on the reproductive health of fwCF is critical. Finally, fwCF and their providers must consider preventative cancer screening.

Menopause in people with cystic fibrosis.

This study aimed to describe the menopause experience of people with cystic fibrosis (CF). We conducted a computer-based cross-sectional survey of women with CF 25 years or older at 10 US CF centers exploring a range of sexual and reproductive health concerns, including menopause. We used descriptive statistics to analyze results. Of 460 participants, 5 (3%) were perimenopausal and 34 (7%) were postmenopausal. Of participants perimenopausal or menopausal (n = 39), 97% reported the following menopausal symptoms occurring at least once a week: most commonly early wake-up (83%); stiffness/soreness in joints, neck, or shoulders (65%); and night sweats (65%). Among menopausal participants, the median self-reported age at menopause was 48.5 years (interquartile range, 5.5 y). Thirty percent experienced worsened CF symptoms during menopause, and 42% experienced worsening CF symptoms after menopause. Twenty-four percent of menopausal participants were on estrogen therapy and 15% on estrogen and progesterone therapy. Three-fourths of participants using hormone therapy reported no change in their CF symptoms. One percent of the 460 survey participants reported discussing menopause with their CF provider, despite 19% wanting to discuss this topic with their CF team. This is the first study to describe menopause symptoms of people with CF. People with CF experience a variety of menopausal symptoms and often report a worsening of their CF symptoms after menopause, suggesting an interplay between female sex hormones and CF. Larger studies are needed comparing the sexual and reproductive health experiences and care needs of people with CF in the menopause transition to the general population.

Clinician attitudes and practices on pregnancy planning and care in cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) are living longer and healthier lives as a result of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, and are pursuing pregnancy. As the number of pregnancies in CF continue to increase, clinician attitudes and practices regarding care of pregnant people with CF remain largely unknown. OBJECTIVE: To evaluate the current attitudes and practices of CF clinicians regarding pregnancy planning and care in CF. METHODS: We conducted a national survey investigating practice patterns related to pregnancy care in CF. We used descriptive statistics to summarize responses and paired t-tests to compare population means. RESULTS: A total of 93 clinicians completed the survey. Eighty-six percent of respondents believed family planning and pregnancy discussions should start before the age of 21 years, of which 67% believed these discussions should occur prior to age 18 years. Our results demonstrate variability in CF clinician comfort and management of various aspects of pregnancy care in CF including 1) potential complications of pregnancy 2) continuation of chronic CF therapies 3) continuation of CFTR modulators during pregnancy and lactation, and 4) approach to treatment of pulmonary exacerbation during pregnancy. CONCLUSIONS: As more people with CF pursue pregnancy in the era of CFTR modulators, CF providers should be initiating discussions surrounding pregnancy early and often. Establishing best practices in the management of pregnancy in CF, expanding peri­pregnancy expertise within the CF community, and future studies investigating the maternal-fetal effects of CF therapies are needed.

Sexual and reproductive health experiences and care of adult women with cystic fibrosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p<0.001;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, p<0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p<0.001 and 5% friends, p<0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p<0.001). 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. CONCLUSION: 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.

Partner perspectives on women's sexual and reproductive healthcare in cystic fibrosis.

BACKGROUND: Women with cystic fibrosis (CF) face many sexual and reproductive health (SRH) concerns. Studies suggest that educating and involving partners in SRH care can improve outcomes. This study investigated partners' perceptions of and preferences for women's SRH care in CF. METHODS: We surveyed partners of women with CF from ten United States (U.S.) CF centers regarding their attitudes and preferences related to CF SRH care. Items assessed experiences with SRH care, sexual relationships, family planning, pregnancy, fertility, and parenthood. We used descriptive statistics to assess results related to the timing, content, setting and delivery of CF SRH care. RESULTS: A total of 94 partners completed the survey (94% male; average age 36±1 years; 70% married; 36% parents). Among those who/whose partners experienced a pregnancy, 48% received preconception counseling and 29% fertility testing/treatment. One-third of all respondents (32%) worried their children would have CF and 86% would undergo CF genetic testing if their CF partner became pregnant. One-third (34%) indicated that they did not have any SRH conversations with their partner's CF team, while 70% would like to have such discussions. The topics that respondents would most like to discuss were pregnancy (50%), fertility (43%), sexual functioning (36%), sexual activity (31%) and parenthood (29%). CONCLUSIONS: Partners report gaps in SRH care and counseling despite the majority wanting to discuss SRH concerns with their partner's CF team. CF partners serve as key supports for women with CF and results can be used to design patient-centered interventions to optimize CF SRH care.

Evaluation of an association between RANKL and OPG with bone disease in people with cystic fibrosis.

BACKGROUND: As people with Cystic Fibrosis (CF) live longer, extra-pulmonary complications such as CF-related bone disease (CFBD) are becoming increasingly important. The etiology of CFBD is poorly understood but is likely multifactorial. Bones undergo continuous remodeling via pathways including RANK (receptor activator of NF-κB)/sRANKL (soluble ligand)/OPG (osteoprotegerin). We sought to examine the association between sRANKL (stimulant of osteoclastogenesis) and OPG levels (inhibitor of osteoclast formation) and CFBD to investigate their potential utility as biomarkers of bone turnover in people with CF. METHODS: We evaluated sRANKL and OPG in plasma from people with CF and healthy controls (HC) and compared levels in those with CF to bone mineral density results. We used univariable and multivariable analysis to account for factors that may impact sRANKL and OPG. RESULTS: We found a higher median [IQR] sRANKL 10,896pg/mL [5,781-24,243] CF; 2,406pg.mL [659.50-5,042] HC; p= 0.0009), lower OPG 56.68pg/mL [36.28-124.70] CF; 583.20pg/mL [421.30-675.10] HC; p < 0.0001), and higher RANKL/OPG in people with CF no BD than in HC (p < 0.0001). Furthermore, we found a higher RANKL/OPG ratio 407.50pg/mL [214.40-602.60] CFBD; 177.70pg/mL [131.50-239.70] CF no BD; p = 0.007) in people with CFBD versus CF without bone disease. This difference persisted after adjusting for variables thought to impact bone health. CONCLUSIONS: The current screening recommendations of imaging for CFBD may miss important markers of bone turnover such as the RANKL/OPG ratio. These findings support the investigation of therapies that modulate the RANK/RANKL/OPG pathway as potential therapeutic targets for bone disease in CF.

Family Planning and Reproductive Health in Cystic Fibrosis.

Family planning in cystic fibrosis (CF) is an increasingly important aspect of care, as improvements in care and outcomes lead to a rise in the number of pregnancies and parenthood in people with CF. This article highlights: (1) Health considerations for people with CF related to pregnancy, contraception, and parenthood. (2) Facets of reproductive planning, fertility, and preconception counseling. (3) Relationship-centered reproductive health discussions.

Management of pregnancy in cystic fibrosis.

With recent therapeutic advances in care, people with cystic fibrosis (CF) are living longer and healthier lives. Development of the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies has led to improved function of the CFTR protein resulting in improved lung function, decreased rates of pulmonary exacerbations and improved nutritional status for the majority of people with CF. Given improved quality and quantity of life, more people with CF are considering becoming pregnant than ever before. Since the first reported pregnancy in a woman with CF in 1960, the management of pregnancy in CF has been of increased interest and is an active field of research. In this review, we aim to discuss the management of pregnancy in CF. We discuss the optimisation of preconception health, management of maintenance CF therapies, and use of CFTR modulators during pregnancy and lactation. We also describe the management of pulmonary exacerbations during pregnancy as well as the unique management of pregnancy in a post-transplant patient with CF. Educational aims: To describe considerations for optimisation of preconception health.To describe the management of chronic CF therapies including CFTR modulators during pregnancy and lactation.To describe treatment of an acute pulmonary exacerbation during pregnancy.To describe the management of pregnancy in individuals with CF following organ transplantation.