In previous reports, we have documented decreased in vitro airway smooth muscle responses to isoproterenol (ISO) in fresh postmortem trachea and bronchus from subjects with fatal asthma. One hypothesis to explain this finding is a decrease in beta-adrenergic receptor (beta AR) numbers on airway smooth muscle. We have now examined the autoradiographic distribution and density of beta AR using [125I]iodocyanopindolol on sections of airway smooth muscle adjacent to those studied functionally. The results have been compared with "normal" trachea and bronchi obtained from persons dying suddenly of nonpulmonary causes. In both trachea and bronchi, there was a 2.8-fold and 2.5-fold increase in specific grain counts, respectively, over smooth muscle from asthmatic airways (n = 6) compared with that determined in normal airways (n = 4, P less than 0.01, unpaired t test). The affinity of the beta AR for the agonist ISO, as determined by competitive binding experiments with increasing concentrations of (-)-ISO on tissue sections, was increased in asthmatic bronchi (IC50 = 80 +/- 13 nM; n = 3) compared with normal bronchi (IC50 = 562 +/- 144 nM; n = 4, P less than 0.05). We conclude that beta AR-mediated relaxant abnormalities in airway smooth muscle in fatal asthma cannot be explained by a decrease in receptor number and, surprisingly, beta AR expression is increased.

BackgroundLipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage. Recently, the relationship between dyslipidemia and pro-inflammatory insults has led to further understanding on the CVD-predisposing effects of dyslipidemia. The aims of the present study were to investigate whether high-fat high-cholesterol (HFHC) diet-induced hyperlipidemia would cause heart damage and to study the potential role of local cardiac lipid dysregulation in the occurrence of cellular injury.MethodsMale Sprague–Dawley rats were divided into normal chow or HFHC diet groups, and sacrificed after 2 or 4 weeks, respectively. Lipid peroxidation marker level was measured. Lipid parameters in the rat hearts were detected. Cardiac damage was evaluated.ResultsHFHC diet increased serum levels of cholesterol and free fatty acids (FFAs) and led to systemic oxidative stress and pro-inflammatory status. Cardiac lipid dysregulation, which was characterized by elevated levels of cholesterol and adipocyte (A)- and heart (H)-fatty acid binding proteins (FABPs), occurred after HFHC diet for 4 weeks. Cardiac damage was further evident with elevated circulating H-FABP levels, increased cardiac interstitial fibrosis and the loss of troponin I.ConclusionOur data demonstrated that HFHC diet led to systemic and cardiac lipid dysregulation, accompanied by systemic oxidative and pro-inflammatory stresses, and these may finally cooperate to cause a series of pathological changes of the heart tissue. Our findings suggest that maintenance of lipid regulation may be essential in the prevention of heart damage.

There has been a rising trend of labor migration globally. Given their alien status within the legal framework of the host countries, migrant domestic workers (MDWs) are especially vulnerable to poor employment conditions that may affect their health status, yet there is still a lack of quantitative evidence in this population hitherto. Using randomly sampled data from a cross-sectional survey of 2,017 live-in female MDWs in Hong Kong, a setting with a high concentration of MDWs, this study examined the association of employment conditions with physical and mental health among the MDWs. We observed poorer physical and mental health status among the MDWs when compared with the general population in Hong Kong. Our findings suggest that employment conditions, including household size, working on the rest day, and housing type, and age were associated with physical health, while employment conditions, including not ever receiving wages on time, frequency of financial remittances, paying the employment agency, having a private room, fulfillment of work-related needs, physical abuse, and discrimination, and sociodemographic characteristics, including age and duration of migration, were associated with mental health. Social support in general did not confound these associations, but religious activities and daily contact with friends were also associated with mental health. Our findings have important implications in designing interventions and policies to improve the physical and mental well-being of this vulnerable migrant population.

BackgroundWe examined the association of housing affordability with physical and mental health in Hong Kong, where there is a lack of related research despite having the worst housing affordability problem in the world, considering potential mediating effect of deprivation.MethodsA stratified random sample of 1978 Hong Kong adults were surveyed. Housing affordability was defined using the residual-income (after housing costs) approach. Health-related quality of life was assessed by the Short-Form Health Survey version 2 (SF-12v2), from which the physical component summary (PCS) and mental component summary (MCS) measures were derived. Multivariable linear regressions were performed to assess associations of housing affordability with PCS and MCS scores, adjusting for sociodemographic, socioeconomic and lifestyle factors. Mediation analyses were also conducted to assess the mediating role of deprivation on the effect of housing affordability on PCS or MCS.ResultsDose–response relationships were observed between housing affordability and mean PCS score (β (95% CI) compared with the highest affordable fourth quartile: −2.53 (−4.05 to −1.01), −2.23 (−3.54 to −0.92), −0.64 (−1.80 to 0.51) for the first, second and third quartiles, respectively) and mean MCS score (β (95% CI): −3.87 (−5.30 to –2.45), −2.35 (−3.59 to −1.11), −1.28 (−2.40 to –0.17) for the first, second and third quartiles, respectively). Deprivation mediated 34.3% of the impact of housing unaffordability on PCS and 15.8% of that on MCS.ConclusionsHousing affordability affects physical and mental health, partially through deprivation, suggesting that housing policies targeting deprived individuals may help reduce health inequality in addition to targeting the housing affordability problem.

Background/Objectives: Frailty has been linked to increased risk of COVID-19 mortality, but evidence is mainly limited to hospitalized older individuals. This study aimed to assess and compare predictive abilities of different frailty and comorbidity measures for COVID-19 mortality in a community sample and COVID-19 inpatients. Design: Population-based cohort study. Setting: Community. Participants: We analyzed (i) the full sample of 410,199 U.K. Biobank participants in England, aged 49-86 years, and (ii) a subsample of 2812 COVID-19 inpatients with COVID-19 data from March 1 to November 30, 2020. Measurements: Frailty was defined using the physical frailty phenotype (PFP), frailty index (FI), and Hospital Frailty Risk Score (HFRS), and comorbidity using the Charlson Comorbidity Index (CCI). PFP and FI were available at baseline, whereas HFRS and CCI were assessed both at baseline and concurrently with the start of the pandemic. Inpatient COVID-19 cases were confirmed by PCR and/or hospital records. COVID-19 mortality was ascertained from death registers. Results: Overall, 514 individuals died of COVID-19. In the full sample, all frailty and comorbidity measures were associated with higher COVID-19 mortality risk after adjusting for age and sex. However, the associations were stronger for the concurrent versus baseline HFRS and CCI, with odds ratios of 20.40 (95% confidence interval = 16.24-25.63) comparing high (>15) to low (<5) concurrent HFRS risk category and 1.53 (1.48-1.59) per point increase in concurrent CCI. Moreover, only the concurrent HFRS or CCI significantly improved predictive ability of a model including age and sex, yielding areas under the receiver operating characteristic curve (AUC) >0.8. When restricting analyses to COVID-19 inpatients, similar improvement in AUC was not observed. This manuscript has been published as a preprint on MedRxiv (

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Airway epithelial cells express beta(2)-adrenergic receptors (beta(2)-ARs), but their role in regulating airway responsiveness is unclear. With the Clara cell secretory protein (CCSP) promoter, we targeted expression of beta(2)-ARs to airway epithelium of transgenic (CCSP-beta(2)-AR) mice, thereby mimicking agonist activation of receptors only in these cells. In situ hybridization confirmed that transgene expression was confined to airway epithelium, and autoradiography showed that beta(2)-AR density in CCSP-beta(2)-AR mice was approximately twofold that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body plethysmography showed that the methacholine dose required to increase enhanced pause to 200% of baseline (ED(200)) was greater for CCSP-beta(2)-AR than for NTG mice (345 +/- 34 vs. 157 +/- 14 mg/ml; P < 0.01). CCSP-beta(2)-AR mice were also less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice acutely increased to 77% over baseline (P < 0.05) but remained unchanged in the CCSP-beta(2)-AR mice. Although both groups were hyperreactive to methacholine 6 h after ozone exposure, the ED(200) for ozone-exposed CCSP-beta(2)-AR mice was equivalent to that for unexposed NTG mice. These findings show that epithelial cell beta(2)-ARs regulate airway responsiveness in vivo and that the bronchodilating effect of beta-agonists results from activation of receptors on both epithelial and smooth muscle cells.