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Symptomatic hepatitis E virus (HEV) infection is sporadic, and usually occurs in a limited number of infected patients, which hinders the investigation of risk factors for clinical outcomes in patients with acute HEV infection. A retrospective cohort study enrolling 1913 patients with symptomatic acute hepatitis E in Beijing 302 Hospital from January 1, 2001 to December 31, 2018 was conducted. The baseline characteristics, clinical features and laboratory data of these HEV infection cases were analyzed. Albumin (ALB), platelet (PLT), alanine aminotransferase (ALT), total bilirubin (T-BiL), international normalized ratio (INR) and serum creatinine (SCR) levels, along with the model for end-stage liver disease (MELD) score, hospitalization days, co-morbidity number and mortality were taken as major parameters for comparing the clinical manifestations in our study. We found that not all pre-existing chronic liver diseases exacerbate clinical manifestations of acute hepatitis E. Alcoholic hepatitis, fatty liver hepatitis, hepatic cyst, drug-induced hepatitis and hepatocellular carcinoma were not significantly associated with mortality of HEV patients. Among all of the comorbidities, end-stage liver diseases (ESLDs, including ascites, cirrhosis, hepatic coma and hepatorenal syndrome), respiratory tract infection and chronic kidney diseases (CKDs, including renal insufficiency and renal failure) were found to remarkably increase the mortality of patients with symptomatic HEV infection. Furthermore, the severity evaluation indexes (SEI), such as MELD score, duration of hospital stay, and co-morbidity number in HEV patients with underlying comorbidities were much worse than that of their counterparts without relevant comorbidities.
Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29-2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03-5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72-0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence.
The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter ≤ 2.5 μm (PM2.5), as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter (PM2.5) and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 (3.1%) were included in this meta-analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic-related than non-traffic-related air pollution. In children, the pooled relative risk (RR) represented significant increases in wheezing (8.2%), cough (7.5%), and lower respiratory illness (15.3%). The pooled RRs in children were 1.091 (95%CI: 1.049, 1.135) for exposure to <25 μg/m3 PM2.5, and 1.126 (95%CI: 1.067, 1.190) for exposure to ≥ 25 μg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.
To characterize the distribution of nontuberculous mycobacteria (NTM) species isolated from pulmonary samples from persons in Asia and their association with pulmonary infections, we reviewed the literature. Mycobacterium avium complex bacteria were most frequently isolated (13%-81%) and were the most common cause of pulmonary NTM disease (43%-81%). Also pathogenic were rapidly growing mycobacteria (M. chelonae, M. fortuitum, M. abscessus). Among all NTM isolated from pulmonary samples, 31% (582/1,744) were considered clinically relevant according to American Thoracic Society diagnostic criteria. Most patients were male (79%) and had a history of tuberculosis (37%). In Asia, high prevalence of rapidly growing mycobacteria and a history of tuberculosis are distinct characteristics of pulmonary NTM disease. This geographic variation is not well reflected in the American Thoracic Society criteria for NTM infections and could be incorporated in future guidelines.
Microbial point-of-care testing (POCT) has potential to revolutionize clinical care. Understanding the prognostic value of microbes identified from the upper respiratory tract (a convenient sampling site) is a necessary first step to understand potential for upper respiratory tract POCTs in assisting antimicrobial treatment decisions for respiratory infections (RTIs). The aim was to investigate the relationship between upper respiratory tract microbial detection and disease prognosis, including effects of antimicrobial use.
Respiratory tract infections are underestimated, as they are mild and generally not incapacitating. In clinical medicine, however, these infections are considered a prevalent problem. By 2030, the third most comprehensive reason for death worldwide will be chronic obstructive pulmonary disease (COPD), according to the World Health Organization. The current arsenal of anti-inflammatory drugs shows little or no benefits against COPD. For thousands of years, herbal drugs have been used to cure numerous illnesses; they exhibit promising results and enhance physical performance. Ginseng is one such herbal medicine, known to alleviate pro-inflammatory chemokines and cytokines (IL-2, IL-4, IFN-γ, TNF-α, IL-5, IL-6, IL-8) formed by macrophages and epithelial cells. Furthermore, the mechanisms of action of ginsenoside are still not fully understood. Various clinical trials of ginseng have exhibited a reduction of repeated colds and the flu. In this review, ginseng's structural features, the pathogenicity of microbial infections, and the immunomodulatory, antiviral, and anti-bacterial effects of ginseng were discussed. The focus was on the latest animal studies and human clinical trials that corroborate ginseng's role as a therapy for treating respiratory tract infections. The article concluded with future directions and significant challenges. This review would be a valuable addition to the knowledge base for researchers in understanding the promising role of ginseng in treating respiratory tract infections. Further analysis needs to be re-focused on clinical trials to study ginseng's efficacy and safety in treating pathogenic infections and in determining ginseng-drug interactions.
Trichodysplasia spinulosa polyomavirus causes trichodysplasia spinulosa, a skin infection, in immunocompromised persons, but the virus is rarely detected in respiratory samples. Using PCR, we detected persistent virus in respiratory and skin samples from an immunocompromised boy with respiratory signs but no characteristic skin spicules. This virus may play a role in respiratory illness.
The respiratory tracts of turkeys play important roles in the overall health and performance of the birds. Understanding the bacterial communities present in the respiratory tracts of turkeys can be helpful to better understand the interactions between commensal or symbiotic microorganisms and other pathogenic bacteria or viral infections. The aim of this study was the characterization of the bacterial communities of upper respiratory tracks in commercial turkeys using NGS sequencing by the amplification of 16S rRNA gene with primers designed for hypervariable regions V3 and V4 (MiSeq, Illumina). From 10 phyla identified in upper respiratory tract in turkeys, the most dominated phyla were Firmicutes and Proteobacteria. Differences in composition of bacterial diversity were found at the family and genus level. At the genus level, the turkey sequences present in respiratory tract represent 144 established bacteria. Several respiratory pathogens that contribute to the development of infections in the respiratory system of birds were identified, including the presence of Ornithobacterium and Mycoplasma OTUs. These results obtained in this study supply information about bacterial composition and diversity of the turkey upper respiratory tract. Knowledge about bacteria present in the respiratory tract and the roles they can play in infections can be useful in controlling, diagnosing and treating commercial turkey flocks.
Respiratory diseases and its treatments are highly concerned in both the pig industry and human health. However, the composition and distribution of antibiotic resistance genes (ARGs) in swine lower respiratory tract microbiome remain unknown. The relationships of ARGs with mobile genetic elements (MGEs) and lung health are unclear. Here, we characterize antibiotic resistomes of the swine lower respiratory tract microbiome containing 1228 open reading frames belonging to 372 ARGs using 745 metagenomes from 675 experimental pigs. Twelve ARGs conferring resistance to tetracycline are related to an MGE Tn916 family, and multiple types of ARGs are related to a transposase gene tnpA. Most of the linkage complexes between ARGs and MGEs (the Tn916 family and tnpA) are also observed in pig gut microbiomes and human lung microbiomes, suggesting the high risk of these MGEs mediating ARG transfer to both human and pig health. Gammaproteobacteria are the major ARG carriers, within which Escherichia coli harbored >50 ARGs and >10 MGEs. Although the microbial compositions structure the compositions of ARGs, we identify 73 ARGs whose relative abundances are significantly associated with the severity of lung lesions. Our results provide the first overview of ARG profiles in the swine lower respiratory tract microbiome.
The aims of this study were to evaluate the frequency of Achromobacter xylosoxidans infection in a cohort of cystic fibrosis patients, to investigate antimicrobial sensitivity, to establish possible clonal likeness among strains, and to address the clinical impact of this infection or colonization on the general outcome of these patients. The study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Center of the Naples University "Federico II". Sputum samples were checked for bacterial identification. For DNA fingerprinting, pulsed-field gel electrophoresis (PFGE) was carried out. Fifty-three patients (17.6%) had at least one positive culture for A. xylosoxidans; of these, 6/53 (11.3%) patients were defined as chronically infected and all were co-colonized by Pseudomonas aeruginosa. Of the patients, 18.8% persistently carried multidrug-resistant isolates. Macrorestriction analysis showed the presence of seven major clusters. DNA fingerprinting also showed a genetic relationship among strains isolated from the same patients at different times. The results of DNA fingerprinting indicate evidence of bacterial clonal likeness among the enrolled infected patients. We found no significant differences in the forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) when comparing the case group of A. xylosoxidans chronically infected patients with the control group of P. aeruginosa chronically infected patients.
Chung-Sang-Bo-Ha-Hwan (CSBHH) is an herbal prescription widely used to treat various chronic respiratory diseases. To investigate the system-level treatment mechanisms of CSBHH in respiratory tract diseases, we identified 56 active ingredients of CSBHH and evaluated the degree of overlap between their targets and respiratory tract disease-associated proteins. We then investigated the respiratory tract disease-related signaling pathways associated with CSBHH targets. Enrichment analysis showed that the CSBHH targets were significantly associated with various signaling pathways related to inflammation, alveolar structure, and tissue fibrosis. Experimental validation was conducted using phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells by analyzing the mRNA expression levels of biomarkers (IL-1β and TNF-α for inflammation; GSTP1, GSTM1, and PTEN for apoptosis) derived from network pharmacological analysis, in addition to the mucin genes MUC5AC and MUC2, to investigate the phlegm-expelling effect of CSBHH. The mRNA expression levels of these genes were consistent with network pharmacological predictions in a concentration-dependent manner. These results suggest that the therapeutic mechanisms of CSBHH in respiratory tract diseases could be attributed to the simultaneous action of multiple active ingredients in the herbal prescription.
Virus like particles (VLPs) produced by the expression of viral structural proteins can serve as versatile nanovectors or potential vaccine candidates. In this study we describe for the first time the generation of HCoV-NL63 VLPs using baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in tagged or native form, and their assembly to form VLPs was evaluated. Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs was developed. Interestingly, we show that these nanoparticles may deliver cargo and selectively transduce cells expressing the ACE2 protein such as ciliated cells of the respiratory tract. Production of a specific delivery vector is a major challenge for research concerning targeting molecules. The obtained results show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and serve as a delivery platform. This study constitutes an important basis for further development of a promising viral vector displaying narrow tissue tropism.
With the recent SARS-CoV-2 outbreak, the importance of rapid and direct detection of respiratory disease viruses has been well recognized. The detection of these viruses with novel technologies is vital in timely prevention and treatment strategies for epidemics and pandemics. Respiratory viruses can be detected from saliva, swab samples, nasal fluid, and blood, and collected samples can be analyzed by various techniques. Conventional methods for virus detection are based on techniques relying on cell culture, antigen-antibody interactions, and nucleic acids. However, these methods require trained personnel as well as expensive equipment. Microfluidic technologies, on the other hand, are one of the most accurate and specific methods to directly detect respiratory tract viruses. During viral infections, the production of detectable amounts of relevant antibodies takes a few days to weeks, hampering the aim of prevention. Alternatively, nucleic acid-based methods can directly detect the virus-specific RNA or DNA region, even before the immune response. There are numerous methods to detect respiratory viruses, but direct detection techniques have higher specificity and sensitivity than other techniques. This review aims to summarize the methods and technologies developed for microfluidic-based direct detection of viruses that cause respiratory infection using different detection techniques. Microfluidics enables the use of minimal sample volumes and thereby leading to a time, cost, and labor effective operation. Microfluidic-based detection technologies provide affordable, portable, rapid, and sensitive analysis of intact virus or virus genetic material, which is very important in pandemic and epidemic events to control outbreaks with an effective diagnosis.
Members of the chloride channel regulator, calcium-activated (CLCA) family are considered to be modifiers in inflammatory, mucus-based respiratory conditions such as asthma and cystic fibrosis. Previous work has shown substantial differences between human and murine CLCA orthologues that limit the value of mouse models. As an alternative, the cat is an unfamiliar but powerful model of human asthma. We therefore characterized the expression profiles of CLCA proteins in the feline respiratory tract. Identical to other species, the feline CLCA1 protein was immunohistochemically localized to virtually all goblet cells and found to be secreted into the mucus. However, it was not detected in submucosal glands where it is expressed in other species. In contrast to all other species studied to date, feline CLCA2 was not found in submucosal glands or any other airway cells. Similar to mice, but in contrast to man and pigs, the feline respiratory tract was devoid of CLCA4 expression. In the airways of asthmatic cats, CLCA1 was strongly overexpressed, similar to human patients. Therefore, despite some similarities in CLCA1 protein expression and secretion, substantial differences were identified between several feline CLCA family members and their respective orthologues in man, mice and pigs, which must be considered in comparative medicine.
To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including ⍺-diversity, β-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75-46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=-13.30; 95 % CI=-21.72 to -4.88; q=0.02). In addition, the Jaccard index was significantly different between samples from participants with COVID-19 and those from controls at all study time points (PERMANOVA q<0.05 for all comparisons). The abundance of three amplicon sequence variants (ASVs) (one Corynebacterium ASV, Frederiksenia canicola, and one Lactobacillus ASV) were decreased in samples from participants with COVID-19 at all seven study time points, whereas the abundance of one ASV (from the family Neisseriaceae) was increased in samples from participants with COVID-19 at five (71.43 %) of the seven study time points. Our results suggest that mild-to-moderate COVID-19 can lead to alterations of the URT microbiota that persist for several weeks after the initial infection.
Respiratory tract fistulas (or fistulae) are abnormal communications between the respiratory system and the digestive tract or the adjacent organs. The origin can be congenital or, more frequently, iatrogenic and the clinical presentation is heterogeneous. Respiratory tract fistulas can lead to severely reduced health-related quality of life and short survival. Therapy mainly relies on endoscopic surgical interventions but patients often require prolonged hospitalization and may develop complications. Therefore, more conservative regenerative medicine approaches, mainly based on lipotransfer, have also been investigated. Adipose tissue can be delivered either as unprocessed tissue, or after enzymatic treatment to derive the cellular stromal vascular fraction. In the current narrative review, we provide an overview of the main tissue/cell-based clinical studies for the management of various types of respiratory tract fistulas or injuries. Clinical experience is limited, as most of the studies were performed on a small number of patients. Albeit a conclusive proof of efficacy cannot be drawn, the reviewed studies suggest that grafting of adipose tissue-derived material may represent a minimally invasive and conservative treatment option, alternative to more aggressive surgical procedures. Knowledge on safety and tolerability acquired in prior studies can lead to the design of future, larger trials that may exploit innovative procedures for tissue processing to further improve the clinical outcome.
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