Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).

Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study.

BACKGROUND: The H3N8 avian influenza virus (AIV) has been circulating in wild birds, with occasional interspecies transmission to mammals. The first human infection of H3N8 subtype occurred in Henan Province, China, in April, 2022. We aimed to investigate clinical, epidemiological, and virological data related to a second case identified soon afterwards in Hunan Province, China. METHODS: We analysed clinical, epidemiological, and virological data for a 5-year-old boy diagnosed with H3N8 AIV infection in May, 2022, during influenza-like illness surveillance in Changsha City, Hunan Province, China. H3N8 virus strains from chicken flocks from January, 2021, to April, 2022, were retrospectively investigated in China. The genomes of the viruses were sequenced for phylogenetic analysis of all the eight gene segments. We evaluated the receptor-binding properties of the H3N8 viruses by using a solid-phase binding assay. We used sequence alignment and homology-modelling methods to study the effect of specific mutations on the human receptor-binding properties. We also conducted serological surveillance to detect the H3N8 infections among poultry workers in the two provinces with H3N8 cases. FINDINGS: The clinical symptoms of the patient were mild, including fever, sore throat, chills, and a runny nose. The patient's fever subsided on the same day of hospitalisation, and these symptoms disappeared 7 days later, presenting mild influenza symptoms, with no pneumonia. An H3N8 virus was isolated from the patient's throat swab specimen. The novel H3N8 virus causing human infection was first detected in a chicken farm in Guangdong Province in December, 2021, and subsequently emerged in several provinces. Sequence analyses revealed the novel H3N8 AIVs originated from multiple reassortment events. The haemagglutinin gene could have originated from H3Ny AIVs of duck origin. The neuraminidase gene belongs to North American lineage, and might have originated in Alaska (USA) and been transferred by migratory birds along the east Asian flyway. The six internal genes had originated from G57 genotype H9N2 AIVs that were endemic in chicken flocks. Reassortment events might have occurred in domestic ducks or chickens in the Pearl River Delta area in southern China. The novel H3N8 viruses possess the ability to bind to both avian-type and human-type sialic acid receptors, which pose a threat to human health. No poultry worker in our study was positive for antibodies against the H3N8 virus. INTERPRETATION: The novel H3N8 virus that caused human infection had originated from chickens, a typical spillover. The virus is a triple reassortment strain with the Eurasian avian H3 gene, North American avian N8 gene, and dynamic internal genes of the H9N2 viruses. The virus already possesses binding ability to human-type receptors, though the risk of the H3N8 virus infection in humans was low, and the cases are rare and sporadic at present. Considering the pandemic potential, comprehensive surveillance of the H3N8 virus in poultry flocks and the environment is imperative, and poultry-to-human transmission should be closely monitored. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, Hunan Provincial Innovative Construction Special Fund: Emergency response to COVID-19 outbreak, Scientific Research Fund of Hunan Provincial Health Department, and the Hunan Provincial Health Commission Foundation.

Response of cross-correlations between high concentrations of PM 2.5 and O 3 at different time scales to the COVID-19: two trends in BTH and PRD (preprint)

The air pollution in China currently is characterized by high concentrations of fine particulate matter (PM2.5) and ozone (O3). Compared with single high pollution events, these double high pollution (DHP) events (both PM2.5 and O3 are above the National Ambient Air Quality Standards (NAAQS) ) pose a greater threat to public health and environment. However, the studies on the temporal evolution and spatial differences of PM2.5-O3 DHP events is not comprehensive. In 2020, the outbreak of COVID-19 provided a special time window to further understand the cross-correlation between PM2.5 and O3 deeply and thus provide theoretical support for the formulation of regional coordinated control strategies. In this paper, a novel method detrended cross-correlation analysis based on maximum time series of variable time scales (VM-DCCA) is established to compare the cross-correlation between high concentrations of PM2.5 and O3 in Beijing-Tianjin-Heibei (BTH) and Pearl River Delta (PRD) at different time scales. As a result, through DCCA, there is a long-term persistent behavior about the cross-correlation between PM2.5 and O3. Firstly, compared with non COVID-19 period, the PM2.5-O3 DCCA exponents decrease by 4.40% and 2.35% in BTH and PRD respectively during COVID-19 period. Further, through VM-DCCA, the VM-DCCA exponents in PRD weaken rapidly with the increase of time scales, and the decline range are about 23.53% and 22.90% at 28-hour time scale during the non COVID-19 period and COVID-19 period respectively. BTH is completely different. Without significant tendency, its VM-DCCA exponents is always higher than that in PRD at different time scales, which also suggests that the coordinated control of PM2.5 and O3 in BTH is more difficult than that in PRD. Finally, we consider the above results are manifestation of the self-organized criticality (SOC) theory of atmospheric system. The impact of meteorological conditions and atmospheric oxidation capacity (AOC) variation during the COVID-19 period on SOC state are further discussed.

The Inhibition of RNA Viruses by Amaryllidaceae Alkaloids: Opportunities for the Development of Broad-Spectrum Anti-Coronavirus Drugs.

The global COVID-19 pandemic has claimed the lives of millions and disrupted nearly every aspect of human society. Currently, vaccines remain the only widely available medical means to address the cause of the pandemic, the SARS-CoV-2 virus. Unfortunately, current scientific consensus deems the emergence of vaccine-resistant SARS-CoV-2 variants highly likely. In this context, the design and development of broad-spectrum, small-molecule based antiviral drugs has been described as a potentially effective, alternative medical strategy to address circulating and re-emerging CoVs. Small molecules are well-suited to target the least-rapidly evolving structures within CoVs such as highly conserved RNA replication enzymes, and this renders them less vulnerable to evolved drug resistance. Examination of the vast literature describing the inhibition of RNA viruses by Amaryllidaceae alkaloids suggests that future, broad-spectrum anti-CoV drugs may be derived from this family of natural products.