Application of the RE-AIM framework to evaluate the implementation of telehealth pulmonary rehabilitation in a randomized controlled trial among African-American and Hispanic patients with advanced stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Pulmonary rehabilitation (PR) decreases rehospitalization for people with COPD. However, less than 2% receive PR, partly due to lack of referral and sparsity of PR facilities. This disparity is particularly pronounced in African American and Hispanic persons with COPD. Telehealth-provided PR could increase access and improve health outcomes. METHODS: We applied the RE-AIM framework in a post-hoc analysis of our mixed methods RCT comparing referral to Telehealth-delivered PR (TelePR) versus standard PR (SPR) for African American and Hispanic COPD patients hospitalized for COPD exacerbation. Both arms received a referral to PR for 8 weeks, social worker follow-up, and surveys administered at baseline, 8 weeks, 6, and 12 months. PR sessions were conducted twice a week for 90 min each (16 sessions total). Quantitative data were analyzed using 2-sample t tests or nonparametric Wilcoxon tests for continuous data and χ2/Fisher exact tests for categorical data. Logistic regression-estimated odds ratios (ORs) were used for the intention-to-treat primary outcome. Qualitative interviews were conducted at the end of the study to assess adherence and satisfaction and were analyzed using inductive and deductive methods. The goal was to understand Reach (whether the target population was able to be enrolled), Effectiveness (primary outcome was a composite of 6-month COPD rehospitalization and death), Adoption (proportion of people willing to initiate the program), Implementation (whether the program was able to be executed as intended, and Maintenance (whether the program was continued). RESULTS: Two hundred nine people enrolled out of a 276-recruitment goal. Only 85 completed at least one PR session 57/111 (51%) TelePR; 28/98 (28%) SPR. Referral to TelePR compared to SPR did not decrease the composite outcome of 6-month COPD-readmission rate/death (OR1.35;95%CI 0.69,2.66). There was significant reduction in fatigue (PROMIS® scale) from baseline to 8-weeks in TelePR compared to SPR (MD-1.34; ± SD4.22; p = 0.02). Participants who received TelePR experienced improvements from baseline in several outcomes (ie, before and after 8 weeks of PR) in the following: COPD symptoms, knowledge about COPD management, fatigue, and functional capacity. Among the patients who had 1 initial visit, adherence rates were similar (TelePR arm, 59% of sessions; SPR arm, 63%). No intervention-related adverse events occurred. Barriers to PR adoption included difficulty or reluctance to complete medical clearances and beliefs about PR efficacy. Notably, only 9 participants sustained exercise after program completion. Maintenance of the program was not possible due to low insurance reimbursement and sparsity of Respiratory Therapists. CONCLUSIONS: TelePR can reach COPD patients with health disparities and can be successfully implemented. The small sample size and large confidence intervals prevent conclusion about the relative effectiveness of participating in TelePR compared to SPR. However, improved outcomes were seen for those in TelePR as well as in SPR. Increasing adoption of PR and TelePR requires consideration of comorbidity burden, and perception of PR utility, and must facilitate medical clearances. Given the sparsity of SPR locations, TelePR can overcome at least the barrier of access. However, given the challenges to the uptake and completion of PR - many of the additional barriers in PR (both in TelePR and SPR) need to be addressed. Awareness of these real-world challenges will not only inform implementation of TelePR for clinicians seeking to adopt this platform but will also inform study designers and reviewers regarding the feasibility of approaches to patient recruitment and retention.

The clinical impact of the Covid-19 pandemic first wave on patients with cystic fibrosis in New York.

BACKGROUND: People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown. METHODS: We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF. RESULTS: There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19. CONCLUSIONS: The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety.

A Telehealth-Delivered Pulmonary Rehabilitation Intervention in Underserved Hispanic and African American Patients With Chronic Obstructive Pulmonary Disease: A Community-Based Participatory Research Approach.

BACKGROUND: Although home telemonitoring (TM) is a promising approach for patients managing their chronic disease, rehabilitation using home TM has not been tested for use with individuals living with chronic obstructive pulmonary disease (COPD) residing in underserved communities. OBJECTIVE: This study aimed to analyze qualitative data from focus groups with key stakeholders to ensure the acceptability and usability of the TM COPD intervention. METHODS: We utilized a community-based participatory research (CBPR) approach to adapt a home TM COPD intervention to facilitate acceptability and feasibility in low-income African American and Hispanic patients. The study engaged community stakeholders in the process of modifying the intervention in the context of 2 community advisory board meetings. Discussions were audio recorded and professionally transcribed and lasted approximately 2 hours each. Structural coding was used to mark responses to topical questions in interview guides. RESULTS: We describe herein the formative process of a CBPR study aimed at optimizing telehealth utilization among African American and Latino patients with COPD from underserved communities. A total of 5 major themes emerged from qualitative analyses of community discussions: equipment changes, recruitment process, study logistics, self-efficacy, and access. The identification of themes was instrumental in understanding the concerns of patients and other stakeholders in adapting the pulmonary rehabilitation (PR) home intervention for acceptability for patients with COPD from underserved communities. CONCLUSIONS: These findings identify important adaptation recommendations from the stakeholder perspective that should be considered when implementing in-home PR via TM for underserved COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03007485; https://clinicaltrials.gov/ct2/show/NCT03007485.

Association of nesfatin-1 and fat mass in cystic fibrosis.

BACKGROUND: The mechanisms of fat mass (FM) loss in cystic fibrosis (CF) are poorly understood but could represent complex pathways involving dysregulation of appetite-modulating peptides and an amplified inflammatory response. Nesfatin-1 is a newly described peptide that decreases food intake and FM but has not been studied in CF. OBJECTIVES: We hypothesized that changes in the appetite-suppressing hormone nesfatin-1 would be physiological, and levels would be lower in advanced CF patients with lower FM compared to those with milder disease and healthy controls. We determined the levels of the cytokines TNF-α, IL-1ß, and IL-6 as they have been associated with weight loss in disease states. METHODS: Fifty-four adult CF subjects, i.e. 17 with severe, 22 with moderate, and 15 with mild disease, as well as 18 controls were recruited. PFT and body composition analysis (via bioelectrical impedance) were performed. Nesfatin-1 and cytokine levels were determined by ELISA. RESULTS: Contrary to our proposed hypothesis, nesfatin-1 levels were highest in CF patients with severe disease and the lowest FM. A significant negative correlation between nesfatin-1 levels and FM was found only in the severe CF group (r = -0.7, p = 0.003). In forward stepwise regression analysis, only FM was significantly associated with nesfatin-1 levels. Levels of TNF-α and IL-6 were elevated in the severe CF group, but there was no association with either FM or nesfatin-1. CONCLUSION: In advanced CF and low FM, nesfatin-1 plasma levels are significantly increased and inversely correlated with the FM. Our results further suggest that nesfatin-1 exerts its effects independently of TNF-α or IL-6.

Macrophage migration inhibitory factor mediates hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significantly higher than in the control group (P = 0.004 and 0.007, respectively). MIF involvement with hypoxia-induced fibroblast proliferation was examined in both a human cell-line and primary mouse cells from wild-type (mif⁺/⁺) and MIF-knockout (mif⁻/⁻) mice. In vitro, hypoxia-increased MIF mRNA, extracellular MIF protein accumulation and cell proliferation. Inhibition of MIF inflammatory activity reduced hypoxia-induced cell proliferation. However, hypoxia only increased proliferation of mif⁻/⁻ cells when they were supplemented with media from mif⁺/⁺ cells. This growth increase was suppressed by MIF inhibition. In vivo, chronic exposure of mice to a normobaric atmosphere of 10% oxygen increased lung tissue expression of mRNA encoding MIF and accumulation of MIF in plasma. Inhibition of the MIF inflammatory active site, during hypoxic exposure, significantly reduced pulmonary vascular remodeling, cardiac hypertrophy and right ventricular systolic pressure. The data suggest that MIF plays a critical role in hypoxia-induced PH, and its inhibition may be beneficial in preventing the development and progression of the disease.

Ghrelin receptor expression in lymphocytes isolated from adult cystic fibrosis patients.

BACKGROUND: To explore mechanisms of weight loss in cystic fibrosis (CF), we studied ghrelin receptor expression on isolated lymphocytes from CF subjects with different body mass indices (BMIs). Eating behavior is influenced by hormone peptides such as ghrelin, a potent appetite stimulator. However, studies on ghrelin plasma levels in CF showed it to be increased in cachectic subjects, the expected physiological response. OBJECTIVES: (1) To compare ghrelin receptor expression between clinically stable CF subjects with normal BMI, CF subjects with cachexia and healthy controls. (2) To investigate ghrelin receptor expression in the same CF subjects before and after treatment for an acute exacerbation. METHODS: Lymphocytes were isolated from CF patients with normal BMI and low BMI and from controls. Ghrelin receptor quantification was determined via flow cytometry. Body composition was determined by bioelectrical impedance, and plasma levels of ghrelin, TNF-alpha, IL-1 and IL-6 were determined. RESULTS: CF subjects with low BMI had increased inflammation evidenced by increased plasma cytokines and showed decreased lymphocytic ghrelin receptor expression. Ghrelin receptor expression in the CF group with normal BMI was similar to controls; it decreased during an acute exacerbation associated with weight loss and returned to baseline following treatment and recovery of the weight loss. CONCLUSIONS: Differences exist in ghrelin receptor expression in lymphocytes isolated from stable CF patients with different BMIs. These changes may be due to a disordered pathological response to weight loss.

Plasma ghrelin and leptin in adult cystic fibrosis patients.

BACKGROUND: Weight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin. METHODS: Plasma ghrelin, leptin, TNF-alpha, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n=19), moderate (n=30) and severe (n=25). RESULTS: Severe CF patients (% predicted FEV1 27+/-7; median BMI 21 kg/m2) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (-0.35,<0.001), FFM (-0.22,<0.05), FM (-0.41,<0.0001), FEV1 (-0.62,<0.001), TNF-alpha (0.51,<0.0001), IL-1 (0.56,<0.0001), and IL-6 (0.33,<0.01). Leptin correlated (r value, p value) with BMI (0.40,<0.0001), FM (0.56,<0.0001), FEV1 (0.34,<0.05), IL-1 (-0.51,<0.05) and TNF-alpha (-0.43,<0.0001). BMI and FEV1 were independent predictors of ghrelin (-0.35,<0.05;-0.59,<0.001). FM was a predictor of leptin (0.56,<0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-alpha (3.4+/-0.6 vs. 1.2+/-0.4), IL-1 (3.5+/-1 vs. 0.2+/-0.1), IL-6 (17.4+/-4 vs. 2.4+/-2). CONCLUSIONS: Elevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF.