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.

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.

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.