Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as respiratory infections, impaired lung growth and chronic obstructive pulmonary disease have been linked to HAP exposure. Solid fuel smoke is a heterogeneous mixture of various gases and particulates. Cell culture and animal studies with controlled exposure conditions and genetic homogeneity provide important insights into HAP mechanisms. Impaired bacterial phagocytosis in exposed human alveolar macrophages possibly mediates several HAP-related health effects. Lung pathological findings in HAP-exposed individuals demonstrate greater small airways fibrosis and less emphysema compared with cigarette smokers. Field studies using questionnaires, air pollution monitoring and/or biomarkers are needed to better establish human risks. Some, but not all, studies suggest that improving cookstove efficiency or venting emissions may be associated with reduced respiratory symptoms, lung function decline in women and severe pneumonia in children. Current studies focus on fuel switching, stove technology replacements or upgrades and air filter devices. Several governments have initiated major programmes to accelerate the upgrade from solid fuels to clean fuels, particularly liquid petroleum gas, which provides research opportunities for the respiratory health community.
Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against coronavirus disease 2019 (COVID-19) are needed. We have developed an orally-delivered Adenovirus type (Ad) 5-vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here we demonstrated that hamsters vaccinated by the oral or intranasal route had robust and cross-reactive antibody responses. We then induced a post-vaccination infection by inoculating vaccinated hamsters with SARS-CoV-2. Oral- or intranasal-vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters after SARS-CoV-2 challenge. Naïve hamsters exposed in a unidirectional air flow chamber to mucosally-vaccinated, SARS-CoV-2-infected hamsters also had lower nasal swab viral RNA and exhibited fewer clinical symptoms than control animals, suggesting that the mucosal-route reduced viral transmission. The same platform encoding the SARS-CoV-2 spike and nucleocapsid proteins elicited mucosal cross-reactive SARS-CoV-2-specific IgA responses in a phase 1 clinical trial (NCT04563702). Our data demonstrate that mucosal immunization is a viable strategy to decrease SARS-CoV-2 disease and airborne transmission.
Showering produces respirable droplets that may serve to deposit pollutants such as trihalomethane decontamination products, heavy metals, inorganic salts, microbes, or cyanoacterial toxins within the respiratory tract. The extent and importance of this route of indoor exposure depend on the physical characteristics of the aerosol as well as the pollutant profile of the source water. The purpose of this study was to characterize shower-generated aerosols as a function of water flow rate, temperature, and bathroom location. Aerosols were generated within a shower stall containing a mannequin to simulate the presence of a human. Using hot water, the mass median diameter (MMD) of the droplets inside the shower and in the bathroom were 6.3-7.5 um and 5.2-6 µm, respectively. Size was independent of water flow rate. The particle concentration inside the shower ranged from 5 to 14 mg/m 3 . Aerosols generated using cold water were smaller (2.5-3.1 µm) and concentrations were lower (0.02-0.1 mg/m 3 ) inside the shower stall. No aerosols were detected in the bathroom area when cold water was used. The International Commission on Radiological Protection model was used to estimate water deposition in the respiratory tract. For hot water, total deposition ranged from 11 to 14 mg, depending on water flow rate, with approximately 50% of this deposited in the extrathoracic region during assumed mouth breathing, and greater than 86% when nose breathing was assumed. Alveolar deposition was 6-10% and 0.9% assuming oral and nasal breathing, respectively. The consequences deposition of shower water droplets will depend on the nature and extent of any pollutants in the source water.One potential source of human exposure to environmental pollutants is through chemically contaminated domestic tap water. The most obvious route of exposure to contaminants is by ingestion; however, dermal and inhalation exposure may also occur within the home. Several studies have shown that showering increases the likelihood that an organic compound will be volatilized, resulting in human exposure beyond that occurring from ingestion (Backer et al., 2000; Giardino & Hagman, 1996;Kerger et al., 2000;Moya et al., 1999;Prichard & Gesell, 1981). For example, in one study, the blood levels of trihalomethane were highest among individuals showering for 10 min, intermediate for individuals bathing for 10 min, and lowest among those who drank 1 L water from the same source over a 10-min period (Backer et al., 2000). These results support the hypothesis that showering is an important route of exposure for trihalomethanes, and possibly other volatile contaminants in tap water. Copyright © Informa HealthcareAddress correspondence to Yue Zhou, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA. yzhou@lrri.org. Publisher's Disclaimer: Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribut...
Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 (COVID-19). In October 2020, the U.S. FDA approved intravenous RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for nonhospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an intravenous administration of RDV at 10 mg/kg, an about 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed after inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with intravenous RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning about 8 hours after infection. Moreover, the efficacy of inhaled RDV was similar to that of intravenous RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.
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