Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood. Methods: We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman's rank correlation coefficient test. Results: Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated. Conclusion: Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

ß-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.

Efficacy of indoor air purification in the treatment of Artemisia pollen-allergic rhinitis: A randomised, double-blind, clinical controlled trial.

OBJECTIVES: To evaluate the clinical efficacy of a high-efficiency air purifier in patients with allergic rhinitis. DESIGN: We conducted a randomised, double-blind, clinical controlled trial with active and inactive versions of an air purifier. Our study included patients with allergic rhinitis who were sensitive to Artemisia pollen and treatment of the indoor environment using air filtration at night. We evaluated the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City in Shanxi Province, China. SETTING: The First Hospital of Yulin (Yulin City, Shanxi Province, China). PARTICIPANTS: A total of 90 patients with allergic rhinitis who were sensitive to allergens of Artemisia pollen were randomly assigned to one of two groups in equal numbers. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in visual analogue scale scores from baseline. Secondary outcomes were changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores and tolerability scores for the air purifier. RESULTS: Based on the allergy symptom score, we found significant differences in rhinitis symptoms between the groups who used the active versus the inactive air purifier. CONCLUSIONS: The results of our investigation demonstrated the health benefits of particle filtration.

Efficacy of indoor air purification in treating Artemisia (mugwort) pollen allergic rhinitis: study protocol for a randomised controlled trial.

BACKGROUND: Allergic rhinitis (AR) is a worldwide health problem. Allergen avoidance is strongly recommended for AR patients. Air purification can reduce concentrations of particles in indoor air, including those of allergens. Air purifiers have been recommended by clinicians for AR patients, but few studies have focused on the removal of airborne allergens from home environments. Such studies have been limited by a lack of blinding, small samples, or a failure to measure allergen levels, disease activity, or a combination of these factors. This study investigates the efficacy of a high-efficiency air purifier in reducing disease activity in the homes of AR patients sensitive to the allergens produced by Artemisia (mugwort) pollen. METHODS: This is a randomized, double-blind, clinical controlled trial that will test active and inactive versions of an air purifier (Atmosphere®; Amway China). Sixty AR patients sensitive to the allergens produced by Artemisia pollen will be assigned randomly to two groups of equal numbers. All patients will undergo a 4-week treatment period and a 4-week observation period. Evaluation will be conducted at baseline (day 0) and on days 7, 14, 21, 28, and 56. The primary outcome measure will be the difference in visual analog scale scores from baseline. Secondary outcomes will be changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores, and tolerability scores for the air purifier. Side effects of treatment will be recorded. DISCUSSION: Reducing exposure to allergens can reduce the risk of conditions such as AR. We hypothesise that AR patients sensitive to the allergens produced by Artemisia pollen will not suffer symptoms in a pollen-free environment. AR patients can remove pollen from their homes using air purifiers, decreasing the risk of symptoms. We expect that our study results will provide reliable evidence for determining the effects of air-purification therapy. TRIAL REGISTRATION: ChiCTR-INR-17012481 . (Retrospectively registered 26 August 2017).