Indoor air quality (IAQ) plays a critical role in respiratory health, particularly among individuals with asthma. This study evaluated the feasibility of collecting and characterizing IAQ in the homes of Black adults with uncontrolled asthma in New York City. Home environmental audits were conducted at the time that ultrasonic personal air sampling (UPAS v2+) devices were deployed, which continuously collected both time-resolved and integrated air samples over an initial target runtime of two-weeks based on the amp-hours of the external battery. Post-trial interviews were conducted. Thirty devices were successfully deployed and returned; all but five provided sufficient data for analysis for getting a multi-day exposure estimates defined as more than 6 consecutive days of data) for analysis. Average runtime was 13.4 days and mean gravimetric PM2.5 was 72 µg/m3 which is double the Environmental Protection Agency’s cutoff of 35.5 µg/m3, a 24-hour average used to assess exposure and risk. Exposure to household environmental triggers was common. Study procedures were acceptable to participants, demonstrating the feasibility of collecting indoor air samples in apartments of adults with uncontrolled asthma. Elevated indoor PM2.5 levels and frequent exposure to environmental triggers were common and may contribute to poor asthma control. This feasibility study was conducted in NYC, New York, as an administrative supplement to a randomized controlled trial (RCT) (#NCT05685381; registered 1/5/23).

Background The 22-item sinonasal outcome test (SNOT-22) is widely used to evaluate quality of life (QOL) in cystic fibrosis chronic rhinosinusitis (CF-CRS) but lacks formal validation in people with CF (PwCF). This study explores the psychometric properties of the SNOT-22 following elexacaftor/tezacaftor/ivacaftor (ETI) administration. Methods Data from three prospective observational cohort studies investigating the impact of ETI on CF-CRS were pooled across four U.S. centers and used for validity assessments. SNOT-22 scores, Lund-Mackay (LM) computed tomography (CT) sinus scores, and Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores were used to assess test-retest reliability, construct validity, and responsiveness to clinical change in SNOT-22 scores. Results Strong test-retest reliability was observed for the SNOT-22 during the first 6 months post-ETI (N = 53, all r ≥ 0.80, p < 0.001). SNOT-22 intraclass correlation coefficients were strong (0.883) at 3 and 6 months after ETI was initiated and moderate (0.693) across all time points. Mean individual scores in 20 SNOT-22 items decreased from baseline to post-ETI (90.1%, p < 0.05). Moderate convergent validity was observed between pre-treatment SNOT-22 scores and LM scores (r = -0.42, p = 0.002) and CFQ-R respiratory domain scores (r = -0.35, p = 0.025). Conclusions The SNOT-22 is a valid, reliable, and responsive instrument for evaluating CRS-specific QOL in adults with CF, and functions effectively as a unidimensional construct across most of its 22 items.

Rationale: Inhaled corticosteroid (ICS) use is lower in Black adults relative to White adults, even when access to treatment is equal. Lower adherence has been shown to be associated with negative ICS beliefs and a preference for non-pharmacologic treatments. However, these topics are not routinely addressed at medical appointments, leaving primary care providers unaware of why asthma control may be suboptimal. This study describes beliefs regarding pharmacologic (ICS) and non-pharmacological asthma management among Black adults and explores associations between these beliefs and adherence. Methods: We utilized baseline data from a randomized control trial of a brief shared decision-making intervention. Participants (n=106) were Black (self-reported) adults with uncontrolled asthma receiving care at one of four federally qualified health centers (FQHCs) in New York and New Jersey participating in the BREATHE (BRief Evaluation of Asthma THErapy) study. BREATHE is an efficacy-implementation randomized control trial testing a brief shared decision-making intervention that uses motivational interviewing (n =100) against a dose-matched attention control condition (n =100). Participants completed the Medication Adherence Report Scale – Asthma (MARS-A; Likert scale range= 1-5; higher score=higher self-reported adherence; scores < 4.5=poor adherence) and the Conventional and Alternative Management for Asthma questionnaire (CAM-A; two subscales= endorsement of non-pharmacologic treatments (i.e. CAM beliefs; range=1-9) and negative ICS beliefs (range=1-6) where higher scores indicate greater endorsement of CAM beliefs or negative ICS beliefs). We used linear regression to explore associations between adherence and beliefs. Results: See Table 1 for sociodemographic characteristics. Average MARS-A score was 3.53 (SD=0.74); most (75%) participants reported suboptimal adherence. As shown in Table 1, participants endorsed 4.8 of 9 non-pharmacologic asthma self-management behaviors and 2.7 of 6 negative ICS beliefs. Adherence was significantly associated with endorsement of CAM beliefs (β=-0.10; p=.04) and negative ICS beliefs (β=-0.13; p=.01). However, they were not deemed clinically meaningful due to small regression coefficients. Conclusion: Black adults with uncontrolled asthma enrolled in the BREATHE trial reported poor ICS adherence, negative ICS beliefs and a preference for non-pharmacologic approaches to asthma at study enrollment. These beliefs represent modifiable risk factors that have the potential to be improved through the BREATHE intervention.

ABSTRACT Objective Although studies have examined changes in C‐reactive protein (CRP) during pulmonary exacerbations (PEX) in people with cystic fibrosis (PwCF), few have evaluated CRP profiles across age groups. Here, we characterize age‐related CRP responses to PEX treatment. Methods We measured CRP concentrations at the beginning and end of intravenous (IV) antibiotic therapy for PEX in 100 pediatric and 147 adult PwCF at 10 US CF Centers. We examined relationships between CRP and age, lung function, severity of PEX symptoms, and time to next PEX. Results CRP measured at initiation of IV antibiotic treatment for PEX was higher in adults than children, median 8 mg/L (IQR 4, 32) versus 5 mg/L (IQR 2, 10), respectively ( p < 0.001). There was a significant correlation between the initial CRP and drop in lung from baseline to the beginning of IV antibiotics in adults and children. Adjusted CRP dropped in response to PEX treatment more commonly in adults than in children (70% vs. 48%, respectively). The range of treatment responses was greater in adults, in those with higher symptom scores, and in those with more advanced lung disease. In adults elevated CRP at the end of treatment was also associated with incomplete recovery of lung function. CRP at the start of IV antibiotics was inversely related to time until the next PEX. Conclusion In children and adults with CF, CRP is increased at the initiation of IV antibiotic therapy for PEX and declines with treatment. The response is more pronounced in highly symptomatic adults with advanced lung disease.

BACKGROUND:High treatment burden can adversely impact health outcomes in people with cystic fibrosis (PwCF). There is a continued need for medication adherence education and further research to evaluate impact of CF pharmacist interventions in an ambulatory care setting. OBJECTIVE(S):To evaluate whether pharmacist integration into an outpatient adult CF clinic can positively impact patient satisfaction and medication adherence through various pharmacist-based interventions. METHODS:At a single urban medical center, a clinical pharmacist on an adult CF care team conducted comprehensive counseling sessions with PwCF. During these visits, types of pharmacist interventions were documented. Patients were provided a baseline and post-counseling survey to assess satisfaction with the pharmacist visit. Adherence to cystic fibrosis transmembrane regulator (CFTR) modulator and mucolytics were tracked 12 months before and 12 months after the counseling session. RESULTS:A total of 723 pharmacist interventions were performed throughout 100 pharmacist visits in 100 PwCF. Most common interventions were inhaler technique education (17%), drug interaction identification (12%), provision of drug education material (12%), and medication refills (12%). Prior to any intervention, 97% of patients felt they could benefit from a pharmacist visit. Post-counseling survey results demonstrated that 98% of patients found pharmacist counseling to be beneficial. Medication adherence rate prior to pharmacy intervention was 81.9% for CFTR modulators and 62.5% for mucolytics, and 86.9% (p=0.143) and 63.6% (p=0.773), respectively, after pharmacist intervention. CONCLUSION:Integration of a clinical pharmacist within the CF clinic can help improve satisfaction and understanding of medication use among PwCF. Nearly all PwCF favorably perceived pharmacist counseling. We report that various pharmacist interventions including optimizing medication use knowledge, reinforcing adherence strategies, and streamlining timely access to treatment can contribute to enhanced care of PwCF.

Introduction Intrathoracic splenosis (IS) is defined by heterotopic autotransplantation of splenic tissue following trauma or surgery to the spleen. It almost always presents as left sided pleural based masses several years following splenectomy. Diagnosis can often be challenging without use of invasive means such as biopsy or video assisted thoracoscopic surgery (VATS) as it can mimic malignancy. Tc-99m-tagged heat-damaged RBC (Tc-99m-DRBC) scan can be used to detect all ectopic splenic tissue and should be used to diagnose IS noninvasively. Case Report A 62 year old male with a history of Heart Failure with Preserved Ejection Fraction (HFpEF) presented to the hospital with progressive dyspnea, weight gain and hypoxia. He has a remote history of gunshot wound and splenectomy in 1998. He was admitted for management of decompensated heart failure and was treated with aggressive diuresis with significant improvement of his hypoxia however, due to persistent oxygen requirement, a CT chest was obtained. CT found several left sided pleural based masses measuring up to 5.6cm in size which raised concern for the possibility of intrathoracic splenosis given the absence of spleen. The patient clinically improved with diuresis. Tc-99m-DRBC scan was obtained and demonstrated intense tracer uptake within lobulated foci along the left hemidiaphragm and left lateral aspect of the heart which confirmed the IS diagnosis. Discussion Intrathoracic splenosis is a rare disease that could occur after trauma or surgery to the spleen resulting from heterotopic autotransplantation of splenic tissue in the thoracic cavity. The mean interval between initial trauma and discovery of IS is 20 years. Most cases are discovered incidentally however some patients can develop pleuritic symptoms or hemoptysis. IS on imaging often presents as numerous homogenous left-sided pleural based masses. The imaging findings can often be concerning for malignancy – and the differential can include lymphoma, mesothelioma, and sclerosing hemangioma. Although it is a rare diagnosis, a high index of clinical suspicion should be maintained in patients with a history of abdominal trauma or splenectomy in order to avoid invasive procedures including percutaneous biopsy, VATS biopsy, and thoracotomy. Radionuclide “Spleen Scan” utilizes Tc-99m labeled heat-damaged erythrocytes and is a highly sensitive and specific modality for the diagnosis of intrathoracic splenosis as well as ectopic autotransplantation elsewhere including peritoneum and liver. Among patients with left sided pleural based masses it is important to inquire about any prior history of abdominal trauma which is instrumental in the diagnosis of IS noninvasively.

Asthma remains a prevalent and burdensome chronic disease in the United States, disproportionately affecting low-income populations and placing a significant strain on the health care system. Environmental allergen exposure, particularly in urban areas, has been extensively linked to asthma development and exacerbations. Identifying effective strategies for reducing allergen exposure could help mitigate asthma morbidity, decrease health care utilization, and improve patients’ quality of life. Studies evaluating environmental interventions, including home- and school-based allergen reduction strategies, have reported mixed results. Although some interventions, such as targeted allergen reduction, pest management, and air filtration, demonstrate improvements in asthma symptoms and health care utilization, others show limited impact on long-term asthma control and controller medication use. In this review, we assess the impact of environmental allergens on asthma prevalence, morbidity, and health care burden in the United States. We also examine the effectiveness of various allergen-reduction strategies in achieving sustained clinical benefits for asthma management and make practical recommendations for patient care.

Brensocatib, an oral, competitive, and reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces exacerbations and lung function decline in non-cystic fibrosis bronchiectasis (NCFBE). This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of brensocatib in adults with cystic fibrosis (CF), comparing these findings with data from previous trials in healthy adults and in those with NCFBE to inform dose selection for future clinical trials. A phase IIa, single-blind, randomized, placebo-controlled trial was conducted to assess the PK, PD, safety, and tolerability of brensocatib in adults with CF. Participants were randomly assigned to receive once-daily brensocatib (10 mg, 25 mg, or 40 mg) or placebo for 28 days. The study planned enrollment of up to 34 adults, stratified on the basis of their CF transmembrane conductance regulator (CFTR) modulator use, to evaluate the PK profile of brensocatib and its safety compared with placebo. Primary PK parameters, including maximum plasma concentration (Cmax), time to maximum concentration (Tmax), area under the concentration–time curve from 0 to 24 h (AUC0–24), and half-life (t1/2), were determined on day 1 and day 28. Dose-dependency of brensocatib exposure was analyzed, and safety and tolerability were assessed through treatment-emergent adverse events. Data from participants were compared with previous data from healthy adults and from those with NCFBE. A total of 29 participants were randomized to treatment, with 21 stratified to the CFTR modulator group. Baseline characteristics were similar among cohorts. Mean age was 37.9 (standard deviation (SD) 14.6) years, and most participants exhibited mild-to-moderate lung disease. PK analysis showed dose-dependent and predictable brensocatib exposure, with comparable profiles between participants with and without use of CFTR modulators. In addition, PK profiles in participants were comparable to those of healthy adults and of those with NCFBE. Pharmacodynamic analysis revealed dose-dependent reduction in neutrophil serine protease (NSP) activity, reaching saturation around the 25-mg dose, particularly in blood. Brensocatib at all doses was well tolerated with no new identified safety signals. Brensocatib demonstrated consistent PK profiles independent of CFTR therapy and comparable to those of healthy and NCFBE adults. Brensocatib reduced blood and sputum NSP levels. The safety profile was comparable to previous studies, with no new safety concerns identified, supporting the use of similar dosing for adults with CF as for other populations. These findings advocate for further investigation of brensocatib in CF. NCT05090904.

Background and Purpose:Federally Qualified Health Centers (FQHC) are critically important in addressing the unmet healthcare needs of individuals impacted by poverty. We used implementation science frameworks to advance understanding of perceived and actual facilitators and barriers to a novel asthma intervention before initiating a FQHC practice-based clinical trial. Methods:Interviews with clinicians and administrators explored pre-implementation trial considerations. Transcripts were inductively coded using conventional content analysis. Results:Sixteen administrators and/or clinicians (88% female; mean age 49 ± 12.21; 44% Black race; 25% Hispanic ethnicity) from four FQHCs participated. Themes included (1) multi-level factors making successful implementation more or less likely, (2) pandemic-specific concerns with implications for current healthcare delivery challenges, and (3) unintended implementation consequences. Conclusions:Participants were optimistic about the likelihood of successful intervention implementation if challenges were recognized and managed. Combined with other planned assessments, this data may provide a more comprehensive evaluation of clinical trial implementation in FQHCs.

BACKGROUND:Little is known about when people with cystic fibrosis (PwCF) begin to experience olfactory decline, or whether sustained use of novel highly effective modulator therapies (HEMT) is predictive of better olfaction. This study evaluated psychophysical olfactory performance and HEMT-associated olfactory outcomes in children and adults with CF. METHODS:In this cross-sectional installment of a longitudinal study, individuals with a physician-confirmed diagnosis of CF completed questionnaires and psychophysical olfactory assessment (i.e., standardized assessment of olfactory domains involving a battery of olfactory stimuli). HEMT consisted of either elexacaftor-tezacaftor-ivacaftor (ETI) or vezacaftor-tezacaftor-deuivacaftor (VTD). Analysis compared performance between pediatric versus adult cohorts and assessed the impact of HEMT on psychophysical olfactory performance while controlling for age, sex, genotype, and history of sinus surgery. RESULTS:Individuals < 21 years old had better psychophysical olfactory performance than those ≥ 21 years old (61% vs. 24% normosmia). Younger age at the start of HEMT was not associated with lowered odds of threshold hyposmia [OR: 0.73; 95% CI: (0.34, 1.50)] or identification hyposmia [OR: 0.67; 95% CI: (0.35, 1.22)] within this cohort. CONCLUSION:Younger people with CF appear to have relatively preserved psychophysical olfactory function that appears to prematurely decline through early adulthood compared to the general population. Although younger age at the start of HEMT therapy was not associated with better olfactory outcomes, future prospective longitudinal studies could evaluate individuals' olfaction across their lifespan to assess the full impact of HEMT on olfaction.

Background/Objectives: Olfactory dysfunction (OD) is a common symptom among people with cystic fibrosis (PwCF) and contributes to environmental safety concerns, nutritional challenges, and an overall diminished quality of life. OD is perceived to progress along the lifespan in PwCF, often due to worsening sinonasal disease. Among children with cystic fibrosis (CwCF), OD is poorly characterized as limited resources and tolerance contribute to challenges in psychophysical olfactory evaluation among pediatric populations. The Children’s Personal Significance of Olfaction (ChiPSO) questionnaire was recently proposed as a tool to assess olfaction and the importance of olfactory stimulation among children. This pilot study aimed to evaluate the utility of ChiPSO among a cohort of ethnically diverse CwCF. Methods: Individuals aged 7–17 with physician-diagnosed CF were asked to complete questionnaires, including ChiPSO and the brief questionnaire on olfactory dysfunction (bQOD-NS), prior to undergoing psychophysical olfactory evaluation with the U-Sniff Identification test. Potential associations between questionnaires and olfactory performance, pulmonary function, and demographic characteristics were evaluated using Pearson and Spearman correlations, independent-sample t-tests, Wilcoxon rank sum tests, and multiple linear regression. Results: U-Sniff Identification score positively correlated with the overall ChiPSO total score [r(13) = 0.640, p = 0.010] and its environmental subdomain score [r(13) = 0.774, p < 0.001], though not with the food subdomain [r(13) = 0.450, p = 0.093], the social subdomain [r(13) = 0.343, p = 0.2], or bQOD-NS score [r(11) = −0.125, p = 0.7]. Hispanic ethnicity is associated with ChiPSO (p = 0.041). Conclusions: In this preliminary study, olfactory importance increases with olfactory function among an ethnically diverse sample of CwCF, with a preferential influence of olfactory function on personal importance of environmental olfactory information. While these results should be interpreted with limitations imposed by the pilot nature of our sample size, our pilot data highlights associations with early adolescent development of importance of olfaction that can be disrupted in the setting of progressive disease among CwCF.

Rationale: Because people spend as much as 90% of their time indoors, indoor air quality (IAQ) is particularly important to health. Climate change impacts IAQ via multiple mechanisms and gas appliances, the main residential source of methane, drives climate change. Poor IAQ is known to be hazardous to pediatric respiratory health; less is known about its effect on adult respiratory health. Methods: A feasibility pilot of IAQ sampling was conducted. Home environmental audits were completed when UPAS v2+ sampling device were deployed. The device had both a PM2.5 sensor and a filter for gravimetric analysis and calibration of the sensor. Filters were analyzed for particulate matter ≤ 2.5μm in size (PM2.5) and gravimetrical calibrations were conducted for increased precision and accuracy. Target run time was 1-2 weeks. Participants completed a post-trial interview. Results: Thirty Black adults with uncontrolled asthma were enrolled: 27 living in apartments (10 in New York City Housing Authority units), 2 in brownstones, and 1 in a single-family house. Two different deployment approaches were tested. First, the device was plugged into the wall to run for 14-day target (deployment n=23 (77%)); four were unplugged part way through the deployment prompting the use of external battery pack version that could run the device for 8 days without being plugged in (deployment n=7(23%)). All devices were successfully deployed and returned; all but five units provided sufficient data for analysis (> 4 consecutive days of data). Runtimes ≤ two-weeks were due to loss of power e.g., accidental unplugging (4/23) or poor attachment to battery (1/7). Average runtime was 13.3 days (n=25); mean PM2.5 was 72 µg/m3, exceeding World Health Organization recommendations not to exceed 15 µg/m3 over 2-3 days annually. Only three homes had healthy PM2.5 levels and two homes had exceedingly high PM2.5 levels (210 µg/m3; 510 µg/m3). Qualitative interviews identified concerns about potential surreptitious device recordings (n=7;23%) participants. Sixteen participants connected climate change to asthma control and two endorsed non-scientific causes of climate change. Twenty-four participants indicated they wanted to know IAQ results even if remediation was not possible; one did not and five were not asked. There were no withdrawals during the two-week monitoring; 100% of data was collected. Conclusion: This data indicates that a home IAQ study of PM2.5 levels was feasible in populations of Black adults with uncontrolled asthma. The high indoor levels of PM2.5 in most residences is concerning and suggests more work is needed.

Background and purposeOlfactory dysfunction (OD) commonly occurs in patients with sinonasal dysfunction, but the prevalence and severity of olfactory issues in adolescents with cystic fibrosis (AwCF) is unclear. OD may contribute to dietary deficiencies and exacerbate nutritional challenges. We sought to review literature on the effectiveness of medical and surgical management of sinonasal symptoms in AwCF and the associated impact on olfactory function.MethodsWe performed a systematic literature search of PubMed, Embase, Web of Science, and Ebsco CINAHL from 1980 to 2022 per PRISMA-ScR protocols to conduct a scoping review in an effort to compile data on study design, patient demographics, clinical characteristics and outcomes, along with risk of bias.ResultsOf 368 abstracts, 3 articles exclusively evaluated AwCF for a total of 34 patients. Two studies evaluated endoscopic sinus surgery (ESS) and dornase alfa. An additional 6 articles were included for mixed pediatric and adult CF populations totaling 313 patients. Interventions included ESS, elexacaftor-tezacaftor-ivacaftor (ETI), ivacaftor, saline, dornase alfa, hyaluronic acid, and hyaluronic acid-tobramycin combination. Outcome measures included subjective assessment of OD using non-validated (4/9) and validated (4/9) surveys, and psychophysical (1/9) smell testing. Studies evaluating ESS, FESS, dornase alfa, ivacaftor, and both hypertonic and isotonic saline reported statistically significant improvement in OD, whereas ETI failed to improve OD despite improvement in other quality of life measures.ConclusionsThere is limited data regarding the impact of medical and surgical interventions on olfaction for AwCF. Assessment of olfaction was often limited to subjective and qualitative self-report. We suggest that tracking of olfactory outcomes with psychophysical testing is critical in this population with dietary challenges and weight management issues.

Objective To provide interim advice and considerations to the CF Community around CF nutrition in the current era. Methods The Cystic Fibrosis (CF) Foundation organized a multidisciplinary committee to develop a Nutrition Position Paper based on the rapidly changing nutrition landscape in CF, due in part to widespread use of cystic fibrosis transmembrane regulator highly effective modulator therapy (HEMT). Four workgroups were formed: Weight Management, Eating Behavior/Food Insecurity, Salt Homeostasis and Pancreatic Enzyme use. Each workgroup conducted their own focused review of the literature. Results The committee summarized current understanding of issues pertaining to the four workgroup topics and provided 6 key take-aways around CF Nutrition in the new era. Conclusion People with CF (pwCF) are living longer, particularly with the advent of HEMT. The traditional high fat, high calorie CF diet may have negative nutritional and cardiovascular consequences as pwCF age. Individuals with CF may have poor diet quality, food insecurity, distorted body image, and an higher incidence of eating disorders. An increase in overweight and obesity may lead to new considerations for nutritional management, given potential effects of overnutrition on pulmonary and cardiometabolic parameters.

BACKGROUND: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion.RESEARCH QUESTION: Which participant-, catheter-, and catheter management-level attri-butes are associated with increased risk of complications of PICCs among people with CF?STUDY DESIGN AND METHODS: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both. Three categories of composite secondary outcomes were identified: difficult line placement, local soft tissue or skin reactions, and catheter malfunction. Data specific to the participant, catheter placement, and catheter management were collected in a centralized database. Risk factors for primary and secondary outcomes were analyzed by multivariate logistic regression.RESULTS: Between June 2018 and July 2021, 157 adults and 103 children older than 6 years with CF had 375 PICCs placed. Patients underwent 4,828 catheter-days of observation. Of the 375 PICCs, 334 (89%) were # 4.5 F, 342 (91%) were single lumen, and 366 (98%) were placed using ultrasound guidance. The primary outcome occurred in 15 PICCs for an event rate of 3.11 per 1,000 catheter-days. No cases of catheter-related bloodstream infection occurred. Other sec-ondary outcomes developed in 147 of 375 catheters (39%). Despite evidence of practice variation, no risk factors for the primary outcome and few risk factors for secondary outcomes were identified.INTERPRETATION: This study affirmed the safety of contemporary approaches to inserting and using PICCs in people with CF. Given the low rate of complications in this study, ob-servations may reflect a widespread shift to selecting smaller-diameter PICCs and using ultrasound to guide their placement. CHEST 2023; 164(3):614-624

Background Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas. Methods Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS. Results 42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas. Conclusions CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.

BACKGROUND:Triple-combination therapy of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to reduce morbidity and mortality in people with cystic fibrosis (PwCF). Although patient body mass index (BMI) favorably increases with ETI treatment, factors contributing to this improvement are poorly characterized. Olfaction contributes to appetite stimulation and anticipation of eating, where higher rates of olfactory impairment (OI) in PwCF may contribute to malnutrition and BMI instability in this population. METHODS:The authors performed a prospective cohort study analyzing 41 CF patient responses to the Cystic Fibrosis Questionnaire-Revised (CFQR) and the 22-Item Sino-Nasal Outcome Test (SNOT-22) and used generalized estimating equations to understand the change in survey variables from being untreated (baseline) to undergoing 3 months of ETI therapy (follow-up). RESULTS:Patients reported significant improvement in their sense of smell at follow-up (p = 0.0036). Their improvements in sense of smell were not confounded by changes in rhinologic or extranasal rhinologic symptoms. Self-reported quality of life (QoL) improved after 3 months of ETI therapy (p = < 0.0001) as did BMI (p = < 0.0001), but improved sense of smell did not independently mediate these changes in QoL and BMI. CONCLUSION:Our results support the impression that ETI therapy improves CF-associated rhinologic symptoms and reverses OI, while contributing to improvement in rhinologic QoL. Sense of smell is not an independent mediator of improved QoL and BMI in this population, suggesting that other factors may have a stronger role in these realms. However, given the subjective improvement in sense of smell, additional evaluation of OI using psychophysical chemosensory assessment will clarify the connection between olfaction, BMI, and QoL in PwCF.

Background: Engaging populations who have been historically underrepresented in biomedical research (UBR) in intervention development can increase the diversity of trial participants and enhance the tailoring of interventions to improve clinical outcomes in populations experiencing disparities. Aims: To understand preferences for an asthma management decision-making intervention in low-income, racially, and ethnically diverse adults in safety-net primary care practices. Methods: We conducted six focus groups with UBR adults with asthma; an interview guide directed questions. An interdisciplinary team performed content analysis and used an iterative coding process to inform subsequent analysis. Results: Thirty-four individuals (100% self-reported Black race and 18% Hispanic ethnicity; 71% female; mean age 49±15, 58% with uncontrolled asthma as measured by the Asthma Control Questionnaire) were recruited from four safety-net primary care practices in New York and New Jersey. Four themes were identified from analysis of the focus group transcripts: 1) interactions that patients desire with clinicians and clinic staff; 2) preferences for asthma management decision making; 3) current asthma management strategies; and 4) (dis)trust in providers and treatment. Conclusions: This important pre-implementation data, in combination with intra- and post-trial assessments, provides comprehensive implementation metrics to consider when planning trials in safety-net primary care sites. Such community-informed research may increase recruitment of diverse participants to clinical trials and identify intervention targets that matter most to the community.