Bacterial lysate add-on therapy in adult and childhood asthma: a systematic review and meta-analysis.

Background: It has been proposed that bacterial lysates may serve as a suitable immunomodulatory oral medication to improve and control asthma symptoms. However, the difference in its efficacy in adults and children remains unclear. Methods: Randomized controlled trials (RCTs) evaluating OM-85 add-on therapy in asthma patients up to December 2021 were searched using PubMed, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, and WP (WeiPu) database. Risk of bias was evaluated using the Cochrane risk of bias assessment tool. Results: A total of 36 studies were included. The results showed that OM-85 add-on treatment provided a 24% improvement in asthma symptom control [relative rates (RR) =1.24, 95% confidence intervals (CI): 1.19-1.30], and also significantly improved lung function, increased numbers of T-lymphocytes and the subtypes, and elevated levels of interferon-γ (IFN-γ), interleukin-10 (IL-10), and IL-12. Levels of serum immunoglobulin E (IgE), eosinophil cationic protein (ECP) and pro-inflammatory cytokines (including IL-4 and IL-5) were suppressed in the OM-85 add-on treatment group. Moreover, OM-85 add-on treatment showed more prominent effects in asthmatic children than in asthmatic adults. Conclusions: OM-85 add-on therapy showed important clinical benefits for patients with asthma, especially asthmatic children. Further studies focusing on the immunomodulatory function of OM-85 in personalized asthma treatment are warranted.

Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

Rural environment reduces allergic inflammation by modulating the gut microbiota.

Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.

Important Role of Immunological Responses to Environmental Exposure in the Development of Allergic Asthma.

Allergic asthma is a public health problem that affects human health and socioeconomic development. Studies have found that the prevalence of asthma has significantly increased in recent years, which has become particularly pronounced in developed countries. With rapid urbanization in China in the last 3 decades, the prevalence of asthma has increased significantly in urban areas. As changes in genetic backgrounds of human populations are limited, environmental exposure may be a major factor that is responsible for the increased prevalence of asthma. This review focuses on environmental components of farms and rural areas that may have protective effects in reducing the development of asthma. Farm and rural related microorganism- and pathogen-associated molecular patterns are considered to be important environmental factors that modulate host's innate and adaptive immune system to induce protection effects later in life. Environmental microbial-related immunotherapy will also be discussed as the future research direction for the prevention of allergic asthma.