Circulating CC16 and asthma: a population-based, multi-cohort study from early childhood through adult life

RATIONALE: CC16 is an anti-inflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively. OBJECTIVES: To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. METHODS: We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: TCRS (years 6-36; N-participants=814, N-observations=3042), BAMSE (years 8-24; Ns=2547, 3438), and MAAS (years 5-18, Ns=745, 1626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms. MEASUREMENTS AND MAIN RESULTS: 1) After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjOR per 1-SD CC16 decrease: 1.20[95%CI 1.12-1.28];P<0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjRRR: 1.40[1.24-1.57];P<0.0001), was confirmed for both atopic and non-atopic asthma, and was independent of lung function impairment. 2) After adjustment for known predictors of persistent asthma, asthmatic children in the lowest CC16 tertile had a nearly 4-fold increased risk for having frequent symptoms persisting into adult life, compared with asthmatic children in the other two CC16 tertiles (meta-analyzed adjOR: 3.72[1.78-7.76];P<0.0001). CONCLUSIONS: Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through mid-adult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO)

Background: Italy has one of the world\u2019s oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertensionmedicationsmay increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were 65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which 65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide