Food insecurity screening and local food access: Contributions to nutritional outcomes among children and adults with cystic fibrosis in the United States.

BACKGROUND: As the nutritional status of people with CF (PwCF) is associated with their socioeconomic status, it is important to understand factors related to food security and food access that play a role in the nutritional outcomes of this population. We assessed the contributions of CF program-level food insecurity screening practices and area-level food access for nutritional outcomes among PwCF. METHODS: We conducted a cross-sectional analysis of 2019 data from the U.S. CF Patient Registry (CFFPR), linked to survey data on CF program-level food insecurity screening and 2019 patient zip code-level food access. Pediatric and adult populations were analyzed separately. Nutritional outcomes were assessed with annualized BMI percentiles (CDC charts) for children and BMI (kg/m2) for adults, with underweight status defined as BMIp <10% for children and BMI <18.5 kg/m2 for adults, and overweight or obese status defined as BMIp >85% for children and BMI >25 kg/m2 for adults. Analyses were adjusted for patient sociodemographic and clinical characteristics. RESULTS: The study population included 11,971 pediatric and 14,817 adult PwCF. A total of 137 CF programs responded to the survey, representing 71% of the pediatric sample and 45% of the CFFPR adult sample. The joint models of nutritional status as a function of both program-level food insecurity screening and area-level food access produced the following findings. Among children with CF, screening at every visit vs less frequently was associated with 39% lower odds of being underweight (OR 0.61, p = 0.019), and the effect remained the same and statistically significant after adjusting for all covariates (aOR 0.61, p = 0.047). Residence in a food desert was associated both with higher odds of being underweight (OR 1.66, p = 0.036; aOR 1.58, p = 0.008) and with lower BMIp (-4.81%, p = 0.004; adjusted -3.73%, p = 0.014). Among adults with CF, screening in writing vs verbally was associated with higher odds of being overweight (OR 1.22, p = 0.028; aOR 1.36, p = 0.002) and higher BMI (adjusted 0.43 kg/m2, p = 0.032). Residence in a food desert was associated with higher odds of being underweight (OR 1.48, p = 0.025). CONCLUSIONS: Food insecurity screening and local food access are independent predictors of nutritional status among PwCF. More frequent screening is associated with less underweight among children with CF, whereas screening in writing (vs verbally) is associated with higher BMI among adults. Limited food access is associated with higher odds of being underweight in both children and adults with CF, and additionally with lower BMI among children with CF. Study results highlight the need for standardized, evidence-based food insecurity screening across CF care programs and for equitable food access to optimize the nutritional outcomes of PwCF.

A phase I study assessing the safety and tolerability of allogeneic mesenchymal stem cell infusion in adults with cystic fibrosis.

BACKGROUND: Mesenchymal stem cells are of particular interest in cystic fibrosis (CF) as a potential therapeutic. Data from pre-clinical studies suggest that allogeneic bone marrow-derived human mesenchymal stem cells (hMSCs) may provide a new therapeutic treatment for CF lung disease by attenuating pulmonary inflammation while decreasing bacterial growth and enhancing antibiotic efficacy. METHODS: Fifteen adults with CF were enrolled in a phase 1 dose-escalation trial of a single intravenous infusion of hMSCs derived from bone marrow aspirates obtained from a single pre-clinically validated healthy volunteer donor. The study employed a 3+3 dose escalation design with subjects receiving a single, intravenous dose of either 1×106, 3×106, or 5×106 hMSCs/kg. Subjects were monitored inpatient for 24 hours and by outpatient visits and telephone calls for 12 months after the infusion. Safety and tolerability were evaluated by monitoring symptoms, patient reported outcome questionnaires, adverse events (AEs), physical exam findings, spirometry, and analyses of safety laboratories. Preliminary evidence for potential efficacy using inflammatory markers in the blood and sputum were also evaluated. RESULTS: No dose-limiting toxicities, deaths or life-threatening adverse events were observed. Most AEs and serious adverse events (SAEs) were consistent with underlying CF. Vital signs, physical exam findings, spirometry and safety laboratory results showed no significant change from baseline. No trends over time were seen in serum or sputum inflammatory markers nor with clinical spirometry. CONCLUSION: Allogeneic hMSC intravenous infusions were safe and well-tolerated in this phase 1 study and warrant additional clinical testing as a potential therapeutic for CF lung disease.

Managing Cystic Fibrosis related diabetes via telehealth during COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) was declared a pandemic on March 11, 2020. In efforts to reduce the risk of transmission, telehealth visits for routine care has significantly increased in the United States. Cystic fibrosis patients have been categorized as a highly vulnerable population to COVID-19 infection. Cystic Fibrosis centers are rapidly assessing and responding to the pandemic to ensure the safety of CF patients. At our Cleveland Clinic Cystic Fibrosis center, we transitioned outpatient clinics to a virtual care model in March 2020. Here, we report the changes that were implemented to optimize diabetes management in CF patients through telehealth during the COVID-19 crisis.

Keep cystic fibrosis patients out of the hospital.

No specific data exists regarding management of patients with cystic fibrosis (CF) who are infected with COVID-19. Based on expert opinion, strategies for outpatient management include use of elexacaftor-tezacaftor-ivacaftor to reduce pulmonary exacerbations, telemedicine, adherence to prescribed regimens, prompt and aggressive treatment of CF exacerbations, and communication about COVID-19 with patients with CF. Strategies for inpatient management may vary due to special precautions to avoid the aerosolization of COVID-19 with the use of nebulized medications and other therapies.

Mortality in Adults with Cystic Fibrosis Requiring Mechanical Ventilation. Cross-Sectional Analysis of Nationwide Events.

Rationale: Survival in patients with cystic fibrosis (CF) is improving over time. Traditionally, there has been concern about high mortality in individuals with CF requiring invasive mechanical ventilation (IMV) for respiratory failure.Objectives: We hypothesized that mortality has decreased over time in this population because of improvements in disease-specific therapies.Methods: The U.S. Nationwide Healthcare Cost and Utilization Project database was used to identify adult patients with CF undergoing IMV between 2002 and 2014. Patients with nonurgent/nonemergent admissions, pregnancy, and encounters related to lung transplantation were excluded. Demographic, geographic, and comorbidities were analyzed. The Cochran-Armitage trend test was used to examine trends in mortality over time. Multivariate mixed effects logistic regression was used to account for possible differences in hospital mortality patterns.Results: We identified 58,799 CF admissions from 2002 to 2014, with 3,727 (6.3%) undergoing IMV. After exclusions, 1,711 admissions remained. In 762 (44.5%) of adult hospitalizations, the patient died. Annual mortality per hospitalization ranged from 29.9 to 55.3%. The Cochran-Armitage trend test suggested an increased probability of survival over time. Factors significantly associated with mortality in multivariate analysis included female sex (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.09), acute renal failure (OR, 1.99; 95% CI, 1.32-3.01), and malnutrition (OR, 1.44; 95% CI, 1.01-2.06). IMV greater than 96 hours was associated with increased mortality in univariate analysis (OR, 1.51; 95% CI, 1.14-1.98); however, after adjustment for potential confounders, the association was no longer statistically significant (OR, 1.05; 95% CI, 0.77-1.43).Conclusions: Mortality per hospitalization in adults with CF who are not bridging to lung transplant and require emergent IMV is 44.5%, suggesting IMV is not futile. Furthermore, mortality decreased over the study period. These finding may help providers, families, and patients with CF weigh the risks and benefits of IMV for respiratory failure.

Risk factors for persistent methicillin-resistant Staphylococcus aureus infection in cystic fibrosis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important pathogen in cystic fibrosis (CF). Over 25% of individuals in the United States with CF are found to have MRSA in respiratory culture specimens, and persistent MRSA infection has been associated with more rapid decline in lung function and increased mortality. The objective of this study was to investigate clinical and demographic characteristics that are associated with the development of persistent MRSA infection in a CF population. METHODS: This was a retrospective cohort study of individuals followed from 2002 to 2012 in the Cystic Fibrosis Foundation Patient Registry. A time-to-event analysis for the development of persistent MRSA infection was performed, and multivariable Cox proportional hazards models were constructed to identify risk factors for infection. RESULTS: The study cohort included 19,434 individuals, of which 5844 would develop persistent MRSA infection. In the adjusted model, pancreatic insufficiency (HR: 1.49; 95% CI: 1.29-1.72), CF related diabetes (HR: 1.13; 95% CI: 1.05-1.20), co-infection with P. aeruginosa (HR: 1.21; 95% CI: 1.13-1.28), and number of hospitalizations/year (HR: 1.09; 95% CI: 1.06-1.12) were all associated with increased risk, whereas higher socio-economic status (HR: 0.87; 95% CI: 0.82-0.93) was associated with a lower risk. Receiving care at a CF center with increased MRSA prevalence was associated with increased risk of MRSA infection: highest quartile (HR: 2.33; 95% CI: 2.13-2.56). CONCLUSIONS: No easily modifiable risk factors for persistent MRSA were identified in this study. However, several risk factors for patients at higher risk for persistent MRSA infection were identified, for example centers with a high baseline MRSA prevalence, and may be useful in designing center-specific MRSA infection prevention and control strategies and/or eradication protocols. Additional studies are needed in order to evaluate if attention to these risk factors can improve clinical outcomes.

Emergence of linezolid-resistant Staphylococcus aureus after prolonged treatment of cystic fibrosis patients in Cleveland, Ohio.

Linezolid (LZD)-resistant Staphylococcus aureus (LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients with S. aureus respiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9; P = 0.001) for a longer duration (546.5 versus 211.9 days; P < 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year; P < 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified by spa typing. According to the Escherichia coli numbering system, seven LRSA isolates contained a G2576T mutation (G2603T, S. aureus numbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T, E. coli numbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyltransferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.