National Jewish Health
  • Denver, CO, United States
Recent publications
Background Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF. Methods We performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets. Results We found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts. Conclusions We identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.
Electronic cigarettes or vaping products have been marketed as a safer alternative to smoking, but very little is known about the health effects in the human lung, particularly in the distal airways, a key site of airway obstruction and destruction in chronic obstructive pulmonary disease that is often exacerbated by viral infections. The aim of this study was to investigate the effects of electronic cigarette vapor (e-vapor) on human distal airway epithelial responses to influenza A virus (IAV) infection. We isolated primary small airway epithelial cells (SAECs) from donor lungs free of lung disease, and cultured them at air–liquid interface (ALI). To measure markers of epithelial injury such as integrity of epithelial barrier structure and function, we selected a regimen of non-toxic, barrier preserving e-vapor exposure of cultured cells to 15 puffs of e-vapor from a commercially available e-cigarette once per day for 3 days, prior to IAV infection. After 72 h of infection, media and cell lysates were collected to measure cytokines involved in inflammatory and antiviral responses. Pre-exposure to e-vapor with IAV infection, compared to IAV infection alone, significantly increased inflammatory and antiviral mediators including IL-8, CXCL10, IFN-beta, and MX1. Our results suggest that e-vapor exposure amplifies human distal airway pro-inflammatory response to IAV infection, independently of the severity of cell injury during viral infection.
Purpose of Review The purpose of this review is to present a review of sleep science, the relationship between sleep and type 1 diabetes, and highlight the current literature on sleep outcomes in adult and pediatric diabetes technology research. Recent Findings Sleep quality is associated with glycemic outcomes, diabetes self-management, and mental health in people with type 1 diabetes. Diabetes technologies, including insulin pumps, continuous glucose monitors, and hybrid closed-loop systems improve glycemic outcomes. However, many people find this technology challenging for a variety of reasons, including increased burden and frequent alarms, especially during the night. The impact of different devices on sleep quality and quantity has been mixed. The newest technology, the hybrid closed-loop systems, offers the best opportunity for nocturnal glycemic regulation and has improved patient and family perspectives on sleep quality. However, objective sleep assessment has not shown significant improvement on sleep duration. Summary Sleep quality and quantity in people with type 1 diabetes are widely recognized as an important component of health care, and the literature regarding the impact of diabetes devices on sleep is increasing. However, sleep disruptions are common and a barrier to device use. Despite finding minimal changes to sleep duration with device use, subjective accounts of sleep quality are overall positive, especially in those using hybrid closed-loop systems. Sleep quantity and quality are important outcomes to consider as diabetes technology continues to evolve.
Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.
Importance: Smoking cessation interventions for hospitalized patients must continue after discharge to improve long-term tobacco abstinence. How health systems can best deliver postdischarge tobacco treatment is uncertain. Objective: To determine if health system-based tobacco cessation treatment after hospital discharge produces more long-term tobacco abstinence than referral to a community-based quitline. Design, setting, and participants: This randomized clinical trial was conducted September 2018 to November 2020 in 3 hospitals in Massachusetts, Pennsylvania, and Tennessee. Cigarette smokers admitted to a study hospital who received brief in-hospital tobacco treatment and wanted to quit smoking were recruited for participation and randomized for postdischarge treatment to health system-based Transitional Tobacco Care Management (TTCM) or electronic referral to a community-based quitline (QL). Both multicomponent interventions offered smoking cessation counseling and nicotine replacement therapy (NRT) for up to 3 months. Data were analyzed from February 1, 2021, to April 25, 2022. Interventions: TTCM provided 8 weeks of NRT at discharge and 7 automated calls with a hospital-based counselor call-back option. The QL intervention sent referrals from the hospital electronic health record to the state quitline, which offered 5 counseling calls and an NRT sample. Main outcomes and measures: The main outcome was biochemically verified past 7-day tobacco abstinence at 6 months. Self-reported point-prevalence and continuous tobacco abstinence and tobacco treatment utilization were assessed 1, 3, and 6 months after discharge. Results: A total of 1409 participants (mean [SD] age, 51.7 [12.6] years; 784 [55.6%] women; mean [SD] 16.4 [10.6] cigarettes/day) were recruited, including 706 randomized to TTCM and 703 randomized to QL. Participants were comparable at baseline, including 216 Black participants (15.3%), 82 Hispanic participants (5.8%), and 1089 White participants (77.3%). At 1 and 3 months after discharge, more TTCM participants than QL participants used cessation counseling (1 month: 245 participants [34.7%] vs 154 participants [21.9%]; 3 months: 248 participants [35.1%] vs 123 participants [17.5%]; P < .001) and pharmacotherapy (1 month: 455 participants [64.4%] vs 324 participants [46.1%]; 3 months: 367 participants [52.0%] vs 264 participants [37.6%]; P < .001). More TTCM than QL participants reported continuous abstinence for 3 months (RR, 1.30; 95% CI, 1.06-1.58) and point-prevalence abstinence at 1 month (RR, 1.22; 95% CI, 1.08-1.35) and 3 months (RR, 1.23; 95% CI, 1.09-1.37) but not at 6 months (RR, 1.14; 95% CI, 0.99-1.29). The primary outcome, biochemically verified point-prevalence abstinence at 6 months, was not statistically significantly different between groups (19.9% vs 16.9%; RR, 1.18; 95% CI, 0.92-1.50). Conclusions and relevance: In this randomized clinical trial, biochemically verified tobacco abstinence rates were not significantly different between groups at the 6-month follow-up. However, the health system-based model was superior to the community-based quitline model throughout the 3 months of active treatment. A longer duration of postdischarge treatment may sustain the superiority of the health system-based model. Trial registration: ClinicalTrials.gov Identifier: NCT03603496.
Immune-related adverse events (irAEs) frequently complicate treatment with immune checkpoint blockade (ICB) targeting CTLA-4, PD-1, and PD-L1, which are commonly used to treat solid and hematologic malignancies. The skin and gastrointestinal (GI) tract are most frequently affected by irAEs. While extensive efforts to further characterize organ-specific adverse events have contributed to the understanding and management of individual toxicities, investigations into the relationship between multi-organ toxicities have been limited. Therefore, we aimed to conduct a characterization of irAEs occurring in both the skin and gut. A retrospective analysis of two cohorts of patients treated with ICB at Memorial Sloan Kettering Cancer Center was conducted, including a cohort of patients with cutaneous irAEs (ircAEs) confirmed by dermatologists (n = 152) and a cohort of patients with biopsy-proven immune-related colitis (n = 246). Among both cohorts, 15% (61/398) of patients developed both skin and GI irAEs, of which 72% (44/61) patients had ircAEs preceding GI irAEs (p = 0.00013). Our study suggests that in the subset of patients who develop both ircAEs and GI irAEs, ircAEs are likely to occur first. Further prospective studies with larger sample sizes are needed to validate our findings, to assess the overall incidence of co-incident irAEs, and to determine whether ircAEs are predictors of other irAEs. This analysis highlights the development of multi-system dermatologic and gastrointestinal irAEs and underscores the importance of oncologists, gastroenterologists, and dermatologists confronted with an ircAE to remain alert for additional irAEs.
RATIONALE Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. OBJECTIVES To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA), trained and validated in the identification of UIP-like features on HRCT (UIP probability), in a large cohort of well characterised patients with progressive fibrotic lung disease, drawn from a national registry. METHODS SOFIA and radiologist-UIP probabilities were converted to PIOPED-based UIP probability categories (UIP not included in the differential: 0-4%, low probability of UIP: 5-29%, intermediate probability of UIP: 30-69%, high probability of UIP: 70-94%, and pathognomonic for UIP:95-100%) and their prognostic utility assessed using Cox proportional hazards modelling. MEASUREMENTS AND MAIN RESULTS On multivariable analysis adjusting for age, gender, guideline based radiologic diagnosis and disease severity (using total ILD extent on HRCT, %predicted FVC, DLco or the CPI), only SOFIA-UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n=83) by expert radiologist consensus (HR1.73, p<0.0001, 95%CI 1.40-2.14). In patients undergoing surgical lung biopsy (SLB) (n=86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (HR1.75, p<0.0001, 95%CI 1.37-2.25). CONCLUSIONS Deep learning-based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared to expert radiologist evaluation or guideline-based histologic pattern. In principle this tool may be useful in multidisciplinary characterisation of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition with poor survival times. We previously published a genome-wide meta-analysis of IPF risk across three studies with independent replication of associated variants in two additional studies. To maximise power and to generate more accurate effect size estimates, we performed a genome-wide meta-analysis across all five studies included in the previous IPF risk genome-wide association studies. We used the distribution of effect sizes across the five studies to assess the replicability of the results and identified five robust novel genetic association signals implicating mTOR (mammalian target of rapamycin) signalling, telomere maintenance and spindle assembly genes in IPF risk.
Background Non-tuberculous Mycobacterium (NTM) infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in eight patients, potentially contributing to lack of treatment response in four cases but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.
The Acute Respiratory Distress Syndrome (ARDS) is a major healthcare problem, accounting for significant mortality and long-term disability. Approximately 25% of patients with ARDS will develop an over-exuberant fibrotic response, termed fibroproliferative ARDS (FP-ARDS) that portends a poor prognosis and increased mortality. The cellular pathologic processes that drive FP-ARDS remain incompletely understood. We have previously shown that the transmembrane receptor-type tyrosine phosphatase Protein Tyrosine Phosphatase-a (PTPa) promotes pulmonary fibrosis in preclinical murine models through regulation of TGF-b signaling. In this study, we examine the role of PTPa in the pathogenesis of FP-ARDS in a preclinical murine model of acid (HCl)-induced acute lung injury. We demonstrate that while mice genetically deficient in PTPa (Ptpra -/- ) are susceptible to early HCl-induced lung injury, they exhibit markedly attenuated fibroproliferative responses. Additionally, early pro-fibrotic gene expression is reduced in lung tissue after acute lung injury in Ptpra -/- mice, and stimulation of naïve lung fibroblasts with the BAL fluid from these mice results in attenuated fibrotic outcomes compared to wild type littermate controls. Transcriptomic analyses demonstrates reduced Extracellular Matrix (ECM) deposition and remodeling in mice genetically deficient in PTPa. Importantly, human lung fibroblasts modified with a CRISPR-targeted deletion of PTPRA exhibit reduced expression of profibrotic genes in response to TGF-β stimulation, demonstrating the importance of PTPa in human lung fibroblasts. Together, these findings demonstrate that PTPa is a key regulator of fibroproliferative processes following acute lung injury and could serve as a therapeutic target for patients at risk for poor long-term outcomes in ARDS.
Severe SARS-CoV-2 infection is associated with strong inflammation and autoantibody production against diverse self-antigens, suggesting a system-wide defect in B cell tolerance. BND cells are a B cell subset in healthy individuals harboring autoreactive but anergic B lymphocytes. In vitro evidence suggests inflammatory stimuli can breach peripheral B cell tolerance in this subset. We asked whether SARS-CoV-2–associated inflammation impairs BND cell peripheral tolerance. To address this, PBMCs and plasma were collected from healthy controls, individuals immunized against SARS-CoV-2, or subjects with convalescent or severe SARS-CoV-2 infection. We demonstrate that BND cells from severely infected individuals are significantly activated, display reduced inhibitory receptor expression, and restored BCR signaling, indicative of a breach in anergy during viral infection, supported by increased levels of autoreactive antibodies. The phenotypic and functional BND cell alterations significantly correlate with increased inflammation in severe SARS-CoV-2 infection. Thus, autoreactive BND cells are released from peripheral tolerance with SARS-CoV-2 infection, likely as a consequence of robust systemic inflammation.
Study Objectives Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures. Methods We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity–Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality. Results After adjustment for all co-variates, increasing PSQI scores (range 0–21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035). Conclusions Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control. Clinical Trial Registration Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/.
Introduction: Motor vehicle crashes (MVC) are the second leading cause of death for adolescents in the United States, with drowsy driving a major contributing factor. Early school start times have been identified as a significant factor that reduces adolescent sleep duration, which in turn contributes to drowsy driving and MVC. This paper examined the longitudinal impact of delaying secondary school start times on self-reported student drowsy driving and teen MVC. Methods: Secondary school students (10th and 11th grade, 51.7% female, 67.8% White) in the United States completed annual surveys 1 year before and 2 years after implementation of later school start times (70-min delay, n range 1642-2452 per year), reporting frequency of drowsy driving (less than once/week vs. at least once/week). Teen (16-18 years) MVC data from the Colorado Department of Transportation for the 2 years before and 2 years after later start time implementation were compared for Arapahoe County (where start times changed) and neighboring Adams County and Douglas County (where start times did not change). Results: With later start times, there was a significant drop in the percent of students who reported frequent drowsy driving (pre-change: 32.6%, post-change: 21.9%, follow-up: 22.8%). Weekday teen MVC rates went down in Arapahoe County (p = .04) during the school year, while no change or increases in MVC rates were seen in neighboring counties. Conclusions: Healthy school start times are important for adolescent health and safety, with study findings highlighting the downstream effects of increased sleep duration following a 70-min delay in secondary school start times on adolescent drowsy driving and teen MVC rates.
Background Whether children and people with asthma and allergic diseases are at increased risk for SARS-CoV-2 infection is unknown. Objective To determine SARS-CoV-2 infection incidence in households with children, and whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. Methods Biweekly nasal swabs and weekly surveys were conducted for six months within 1,394 households (N=4,142 participants) to identify incident SARS-CoV-2 infections from May 2020-February 2021, a pandemic time period largely pre-vaccine and pre-emergence of SARS-CoV-2 variants. Participant/household infection and household transmission probabilities were calculated using time-to-event analyses, and factors associated with infection and transmission risk determined using regression analyses. Results 147 households (261 participants) tested positive for SARS-CoV-2. Household SARS-CoV-2 infection probability was 25.8%; participant infection probability was similar for children (14.0%,CI:8.0-19.6%), teenagers (12.1%,CI:8.2-15.9%), and adults (14.0%,CI:9.5-18.4%). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (aHR=1.04,CI:0.73-1.46), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR=0.50,CI:0.32-0.81); higher BMI was associated with increased infection risk (aHR per 10-point increase:1.09,CI:1.03-1.15). Household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (aOR=0.43,CI:0.19-0.96,p=0.04). Conclusion Asthma does not increase risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, while BMI is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for infection prevention.
Rationale: There are no pharmacologic agents that modify emphysema progression in patients with chronic obstructive pulmonary disease (COPD). Objective: Evaluate the efficacy of losartan, an angiotensin receptor blocker (ARB), to reduce emphysema progression. Methods: The trial was a multicenter randomized placebo-controlled trial, conducted between May 2017 and January 2021. Eligible participants were age ≥40, had moderate to severe airflow obstruction, ≥10 pack-years smoking, mild-moderate emphysema on high-resolution computed tomography (HRCT), and no medical indication for or intolerance of ARBs. Treatment with losartan, 100 mg daily, or matching placebo (1:1) was randomly assigned. The primary outcome was emphysema progression on HRCT over 48 weeks. Secondary outcomes included St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council dyspnea scale, COPD Assessment Test, Physical Function-Short Form 20a (PROMIS 20a). Results: 220 participants were enrolled; 58% were men, 19% were African American; and 24% current smokers. The medians (interquartile ranges) for age were as 65 (61, 73) years, and 48 (36, 59) for percent predicted FEV1 post-bronchodilator. The mean (95% confidence interval) percent emphysema progression was 1.35% (0.67, 2.03) in the losartan group vs 0.66% (0.09, 1.23) in placebo (P = NS). Conclusions: Losartan did not prevent emphysema progression in people with COPD with mild-moderate emphysema. Clinical trial registration available at www. Clinicaltrials: gov, ID: NCT02696564.
Yisha Li,1 Ran Dai,2 Yeongjin Gwon,2 Stephen I Rennard,3 Barry J Make,4 Dinah Foer,5 Matthew J Strand,4 Erin Austin,6 Kendra A Young,1 John E Hokanson,1 Katherine A Pratte,7 Rebecca Conway,1 Gregory L Kinney1 On behalf of COPDGene investigators1Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 2Department of Biostatistics, School of Public Health, University of Nebraska Medical Center, Omaha, NE, USA; 3Division of Pulmonary, Critical Care and Sleep Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Medicine, National Jewish Health, Denver, CO, USA; 5Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; 6Mathematical and Statistical Sciences, University of Colorado Denver, Denver, CO, USA; 7Department of Biostatistics, National Jewish Health, Denver, CO, USACorrespondence: Gregory L Kinney, Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, Tel +1 303-724-4437, Email GREG.KINNEY@CUANSCHUTZ.EDU
e23007 Background: Given the rapid evolution of treatments for advanced melanoma, oncology providers are challenged to stay current on evidence-based recommendations for optimal patient care. Integrating practice-based polling into continuing medical education (CME) activities is a proven way to increase engagement, address knowledge gaps, and assess attitudes on specific topics. Methods: We provided a CME activity designed to educate oncology and dermatology providers on the latest advances regarding the management of advanced BRAFmut+ melanoma. Interspersed engagement opportunities further assessed practice preferences and elucidated persisting educational needs. The CE activity was available for credit from December 31, 2020 to December 30, 2021. Results: 305 medical oncology or dermatology providers who each see an average of 25 patients with melanoma per month participated. These providers scored an average 38% on pretest topics related to the use of triple therapy and patient and/or tumor characteristics that guide clinical decision-making. Post-learning, providers scored 84%, highlighting the impact of the education on knowledge gaps. Notably, while 51% of these providers indicated that they were guessing on the pre-test, the percentage of those who were confident and correct on the post-test rose from 3% to 28%, demonstrating a rise in confidence among participants. While 50% of participants noted a positive perception of triple therapy (BRAF inhibitor + MEK inhibitor + anti-PD1) in the front-line setting, case-based polling questions showed that providers lack consensus regarding the use of combinations of treatments in other clinical scenarios. While 45% would recommend triple therapy in the first-line setting, dual checkpoint inhibitor (CPI)-based treatment is preferred after progression on a first-line CPI or dual-targeted therapy. Conclusions: CME is a useful method to address knowledge gaps regarding evolving treatment options. As data regarding the use of triple therapy for patients with BRAF+ melanoma emerges, oncology and dermatology providers will require further education on how to apply these options in practice.[Table: see text]
Introduction Therapeutic advances have markedly increased life expectancy for those with cystic fibrosis (CF), resulting in a median predicted survival over 50 years. Consequently, people with CF (pwCF) are living through their reproductive years and the rate of pregnancy is rapidly rising. Despite the increased relevance of this topic, multicentre studies investigating the association between maternal health and choices made during pregnancy on maternal and fetal outcomes do not exist. Furthermore, there are very limited data on the outcomes following CF transmembrane conductance regulator (CFTR) modulator use during pregnancy and lactation. Methods and analysis Ma ternal and F eta l O utcomes in the E ra of Modulato rs (MAYFLOWERS) is a prospective, multicentre observational clinical trial which will enrol approximately 285 pregnant pwCF including those who are modulator ineligible and those who choose to continue or discontinue CFTR modulator therapy during pregnancy and lactation. The primary aim of this 35-month study is to assess whether lung function changes during pregnancy differ based on the continued use of modulators or other factors such as pre-existing comorbid conditions. Secondary objectives include evaluation of pregnancy related and obstetrical complications and changes in mental health. Ethics and dissemination The design of this study required special consideration of study burden on pregnant and lactating people with chronic illness in the setting of a substantial number of unanswered questions under these conditions. MAYFLOWERS is the first prospective clinical trial examining pregnancy in CF; the outcomes will guide providers on pregnancy management in pwCF and others with chronic respiratory disease.
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334 members
Jeff Swigris
  • Autoimmune Lung Center and Interstitial Lung Disease Program
Ferdaus Mohd. Altaf Hossain
  • Department of Medicine
Brian J Day
  • Department of Medicine
Brett Fenster
  • Division of Cardiology
James Lewis Crooks
  • Division of Biostatistics and Bioinformatics
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1400 Jackson Street, 80206, Denver, CO, United States
Head of institution
Michael Salem, MD
Website
http://www.nationaljewish.org/
Phone
877.225.5654