The Role of Respiratory Flora in the Pathogenesis of Chronic Respiratory Diseases.

Large quantities of bacteria, including Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.

Smartphone-based multiplex 30-minute nucleic acid test of live virus from nasal swab extract.

Rapid, sensitive and specific detection and reporting of infectious pathogens is important for patient management and epidemic surveillance. We demonstrated a point-of-care system integrated with a smartphone for detecting live virus from nasal swab media, using a panel of equine respiratory infectious diseases as a model system for corresponding human diseases such as COVID-19. Specific nucleic acid sequences of five pathogens were amplified by loop-mediated isothermal amplification on a microfluidic chip and detected at the end of reactions by the smartphone. Pathogen-spiked horse nasal swab samples were correctly diagnosed using our system, with a limit of detection comparable to that of the traditional lab-based test, polymerase chain reaction, with results achieved in ∼30 minutes.

Dysbiosis Signatures of Fecal Microbiota in South African Infants with Respiratory, Gastrointestinal, and Other Diseases.

OBJECTIVE: To determine the association between the fecal microbiota diversity of the infants with different disease conditions, and vitamin A supplementation, antibiotic, and deworming therapies. STUDY DESIGN: In this case-control study, the bacterial community variations and the potential pathogens were identified through 16S ribosomal RNA gene-based amplicon sequencing and quantitative insights into microbial ecology pipeline in fecal samples. The participants were South African infants (mean age, 16 ± 8 months; 17 male and 17 female) hospitalized and diagnosed with gastrointestinal, respiratory, and other diseases. RESULTS: The top phyla of the infants with respiratory disease were Proteobacteria, followed by Firmicutes, which were equally abundant in gastrointestinal disease. A significant difference in Shannon (alpha) diversity index (95% CI, 2.6-4.4; P = .008), among the microbiota of the fecal samples categorized by disease conditions, was observed. In beta diversity analysis of fecal microbiota, remarkable variations were found within the groups of deworming therapy (95% CI, 0.40-0.90; P = .033), disease conditions (95% CI, 0.44-0.86; P < .012) through unweighted and antibiotic therapy (95% CI, 0.20-0.75; P = .007), vitamin A intake (95% CI, 0.10-0.80; P < .033) and disease conditions (95% CI, 0.10-0.79; P = .006) through weighted UniFrac distances. The candidate pathogen associated with the disease groups were identified through analysis of the composition of microbiomes analysis. CONCLUSIONS: This study provides preliminary evidence for the fecal microbiome-derived dysbiosis signature and pathobiome concept that may be observed in young children during illness.

Complications of the surgical treatment of esophageal cancer and microbiological analysis of the respiratory tract.

AIM: The aim of this study was to reduce the severe respiratory complications of esophageal cancer surgery often leading to death. METHODS: Two groups of patients operated on for esophageal cancer were evaluated in this retrospective analysis. The first group was operated between 2006-2011, prior to the implementation of preoperative microbiological examination while the second group had surgery between 2012-2017 after implementation of this examination. RESULTS: In total, 260 patients, 220 males and 40 females underwent esophagectomy. Between 2006-2011, 113 (87.6%) males and 16 (12.4%) females and between 2012-2017, esophagectomy was performed in 107 (81.7%) males and 24 (18.3%) females. In the first cohort, 10 patients died due to respiratory complications. The 30-day mortality was 6.9% and 90-day was 9.3%. In the second cohort, 4 patients died from respiratory complications. The 30-day mortality was 1.5% and 90-day mortality was 3.1%. With regard to the incidence of respiratory complications (P=0.014), these occurred more frequently in patients with sputum collection, however, severe respiratory complications were more often observed in patients without sputum collection. Significantly fewer patients died (P=0.036) in the group with sputum collection. The incidence of respiratory complications was very significantly higher in the patients who died (P<0.0001). CONCLUSION: The incidence of severe respiratory complications (causing death) may be reduced by identifying clinically silent respiratory tract infections.

Functional effects of the microbiota in chronic respiratory disease.

The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.

Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied. METHODS: This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models. DISCUSSION: We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.

[European birth cohorts: Early life exposure to microorganisms and health impact]. / Cohortes de naissances européennes : exposition aux micro-organismes et impact sanitaire.

In recent years, many birth cohorts have been initiated in Europe, to assess the early life microbiological exposure of children in the indoor environment and better understanding the different effects (adverse/protectors) on health. The results of 12 European cohorts, with different methodologies for exposure and allergic risk assessment are summarized in this review. Four meta-analyzes of cohort are presented too. Microbiological researches in indoor environment seem to turn to a metrology of microbiological exposure, but few studies provide real quantitative data. Thus, the establishment of dose-effect relationship is not possible and can only be done by having a global view of the situation, provided by an identical metrological approach in the different studies, in a large-scale, in the context of large birth cohorts with children followed with strict criteria to establish the clinical diagnosis.

Factors predicting antibiotic prescription and referral to hospital for children with respiratory symptoms: secondary analysis of a randomised controlled study at out-of-hours services in primary care.

OBJECTIVES: Acute respiratory infections and fever among children are highly prevalent in primary care. It is challenging to distinguish between viral and bacterial infections. Norway has a relatively low prescription rate of antibiotics, but it is still regarded as too high as the antimicrobial resistance is increasing. The aim of the study was to identify predictors for prescribing antibiotics or referral to hospital among children. DESIGN: Secondary analysis of a randomised controlled study. SETTING: 4 out-of-hours services and 1 paediatric emergency clinic in Norwegian primary care. PARTICIPANTS: 401 children aged 0-6 years with respiratory symptoms and/or fever visiting the out-of-hours services. OUTCOMES: 2 main outcome variables were registered: antibiotic prescription and referral to hospital. RESULTS: The total prescription rate of antibiotics was 23%, phenoxymethylpenicillin was used in 67% of the cases. Findings on ear examination (OR 4.62; 95% CI 2.35 to 9.10), parents' assessment that the child has a bacterial infection (OR 2.45; 95% CI 1.17 to 5.13) and a C reactive protein (CRP) value >20 mg/L (OR 3.57; 95% CI 1.43 to 8.83) were significantly associated with prescription of antibiotics. Vomiting in the past 24 hours was negatively associated with prescription (OR 0.26; 95% CI 0.13 to 0.53). The main predictors significantly associated with referral to hospital were respiratory rate (OR 1.07; 95% CI 1.03 to 1.12), oxygen saturation <95% (OR 3.39; 95% CI 1.02 to 11.23), signs on auscultation (OR 5.57; 95% CI 1.96 to 15.84) and the parents' assessment before the consultation that the child needs hospitalisation (OR 414; 95% CI 26 to 6624). CONCLUSIONS: CRP values >20 mg/L, findings on ear examination, use of paracetamol and no vomiting in the past 24 hours were significantly associated with antibiotic prescription. Affected respiration was a predictor for referral to hospital. The parents' assessment was also significantly associated with the outcomes. TRIAL REGISTRATION NUMBER: NCT02496559; Results.

Association between Outdoor Fungal Concentrations during Winter and Pulmonary Function in Children with and without Asthma.

Outdoor fungi are important components of airborne particulate matter (PM). However, the associations between pulmonary function and outdoor fungi are less well known compared to other airborne PM constituents. The objective of this study was to investigate the association between outdoor fungi and pulmonary function in children. Morning peak expiratory flow (PEF) rates were measured daily in 339 schoolchildren (including 36 with asthma), aged 10 to 12, 2 to 27 February 2015. Airborne PM was collected on filters, using a high volume air sampler, each day during the study period. The daily concentration of outdoor fungi-associated PM was calculated using a culture-based method. A linear mixed model was used to estimate the association between PEF values and daily concentrations of outdoor fungi, and the daily levels of suspended PM (SPM) and PM ≤ 2.5 µm (PM2.5). An increase in the interquartile range (46.2 CFU/m³) for outdoor fungal concentration led to PEF changes of -1.18 L/min (95% confidence interval, -2.27 to -0.08) in all children, 1.22 L/min (-2.96 to 5.41) in children without asthma, and -1.44 L/min (-2.57 to -0.32) in children with asthma. Outdoor fungi showed a significant negative correlation with PM2.5 levels (r = -0.4, p = 0.04), but not with SPM (r = ‒0.3, p = 0.10) levels. Outdoor fungi may be associated with pulmonary dysfunction in children. Furthermore, children with asthma may show greater pulmonary dysfunction than those without asthma.

The 'Practical Approach to Lung Health' in sub-Saharan Africa: a systematic review.

SETTING: There is a high burden of respiratory disease in sub-Saharan Africa. To address this problem, the World Health Organization launched the 'Practical approach to Lung Health' (PAL), i.e., locally applicable integrated syndromic algorithms, to improve primary care management of these diseases. OBJECTIVE: To examine the evidence for the impact of PAL on the diagnosis and management of tuberculosis (TB) and other common respiratory problems in sub-Saharan Africa. DESIGN: A systematic review of MEDLINE (1998-2015), EMBASE (1998-2015) and CINAHL (1998-2015) was conducted to find trials evaluating PAL implementation in sub-Saharan Africa. RESULTS: Five studies were found, evaluating three PAL variations: PAL in South Africa (PALSA), PALSA with integrated human immunodeficiency virus treatment (PALSA PLUS) and PAL in Malawi using lay health workers (PALM/LHW). PALSA increased TB diagnosis (OR 1.72, 95%CI 1.04-2.85), as did PALSA PLUS (OR 1.25, 95%CI 1.01-1.55). Cure or completion rates in retreatment cases in PALSA and PALSA PLUS were significantly improved (OR 1.78, 95%CI 1.13-2.76). PALM/LHW, which examined TB treatment success, found no significant improvement (P = 0.578). CONCLUSION: The limited research performed shows that PAL can be effective in TB diagnosis and partial treatment success; however, more evidence is needed to assess its effects on other respiratory diseases, especially in wider sub-Saharan Africa.

Respiratory disorders associated with occupational inhalational exposure to bioaerosols among wastewater treatment workers of petrochemical complexes.

BACKGROUND: Workers in wastewater treatment plants are exposed to a wide range of chemicals as well as biological contaminants. OBJECTIVE: To ascertain whether exposure to bio-aerosols under the normal working conditions in wastewater treatment plants is associated with any significant changes in the prevalence of respiratory symptoms and lung function capacities. METHODS: 198 employees of wastewater treatment plants and 99 unexposed persons were studied. American thoracic society (ATS) standard respiratory symptom questionnaire was used to determine the prevalence of respiratory symptoms. Pulmonary function tests were conducted for each participant. RESULTS: The prevalence of respiratory symptoms among exposed persons was significantly higher than that of unexposed people. Mean values of most pulmonary function test parameters were significantly lower in the exposed compared to the comparison group persons. CONCLUSION: Increased prevalence of respiratory symptoms and decrements in pulmonary function test parameters may be attributed to exposure to bio-aerosols released from wastewater treatment plants.

Respiratory complications in outpatient endoscopy with endoscopist-directed sedation.

BACKGROUND AND AIMS: Respiratory complications represent an important adverse event of endoscopic procedures. We screened for respiratory complications after endoscopic procedures using a questionnaire and followed-up patients suggestive of respiratory infection. METHOD: In this prospective observational, multicenter study performed in Outpatient practices of gastroenterology we investigated 15,690 patients by questionnaires administered 24 hours after the endoscopic procedure. RESULTS: 832 of the 15,690 patients stated at least one respiratory symptom after the endoscopic procedure: 829 patients reported coughing (5.28%), 23 fever (0.15%) and 116 shortness of breath (SOB, 0.74%); 130 of the 832 patients showed at least two concomitant respiratory symptoms (107 coughing + SOB, 17 coughing + fever, 6 coughing + coexisting fever + SOB) and 126 patients were followed-up to assess their respiratory complaints. Twenty-nine patients (follow-up: 22.31%, whole sample: 0.18%) reported signs of clinically evident respiratory infection and 15 patients (follow-up: 11.54%; whole sample: 0.1%) received therefore antibiotic treatment. Coughing or vomiting during the endoscopic procedure resulted in a 156.12-fold increased risk of respiratory complications (95% CI: 67.44 - 361.40) and 520.87-fold increased risk of requiring antibiotic treatment (95% CI: 178.01 - 1524.05). All patients of the follow-up sample who coughed or vomited during endoscopy developed clinically evident signs of respiratory infection and required antibiotic treatment while this occurred in a significantly lower proportion of patients without these symptoms (17.1% and 5.1%, respectively). CONCLUSIONS: We demonstrated that respiratory complications following endoscopic sedation are of comparably high incidence and we identified major predictors of aspiration pneumonia which could influence future surveillance strategies after endoscopic procedures.

A review of bio-aerosol exposures and associated health effects in veterinary practice.

INTRODUCTION: Occupational exposure to bio-aerosols has been linked to various health effects. This review presents an overview of bio-aerosol exposure levels in veterinary practices, and investigates the possibility of health effects associated with bio-aerosol exposure. METHODS: A systematic literature search was carried out in PubMed. Publications were included if they provided information on bio-aerosol exposure and related health effects through veterinary practice and other professions with similar exposures, occupationally exposed to animals. RESULTS: Few studies in veterinary settings showed that substantial bio-aerosol exposure levels (e.g. endotoxin and ß(1→3)-glucan) were likely occur when handling farm animals and horses. Exposure levels are comparable to those levels observed in farming which have been associated with respiratory health effects. Animal specific allergen exposures have hardly been studied, but showed to be measurable in companion animal clinics and dairy barns. The Findings of the few studies available among veterinary populations, particularly those working with farm animals and horses, are indicative of an elevated risk for developing respiratory symptoms. Studies among pig farmers, exposed to similar environments as veterinarians, strongly confirm that veterinary populations are at an increased risk of developing respiratory diseases in relation to bio-aerosol exposure, in particular endotoxin. Exposure to animal allergens during veterinary practice may cause allergic inflammation, characterized by IgE-mediated reactions to animal allergens. Nonetheless, the occurrence of sensitization or allergy against animal allergens is poorly described, apart from laboratory animal allergy, especially known from exposure to rats and mice. CONCLUSION: Veterinary populations are likely exposed to elevated levels of bio-aerosols such as endotoxins, ß(1→3)-glucans, and some specific animal allergens. Exposures to these agents in animal farmers are associated with allergic and non-allergic respiratory effects, proposing similar health effects in veterinary populations.

The clinical significance of Nicoletella semolina in horses with respiratory disorders and a screening of the bacterial flora in the airways of horses.

Nicoletella semolina, a member of the family Pasteurellaceae, can be isolated from the airways of horses with respiratory disorders. However, its role as a potential or opportunistic pathogen is not clear nor is its presence as part of the normal flora. We therefore investigated the presence and bacterial load of N. semolina in healthy and diseased horses. Samples from a healthy control group were compared with samples from the routine analysis of horses with a clinical history of respiratory disorders. A total of 1770 nose swabs and 1132 tracheal aspirate samples were analysed and subjected to conventional bacteriological examination. N. semolina was isolated from 12 (6%) of 207 nose samples from the healthy control group and from 42 (3%) of 1563 samples from horses with respiratory disorders. In tracheal aspirate, N. semolina was isolated from 7 (3%) of 211 samples from the control group and 49 (5%) of 921 samples from horses with respiratory disorders. Other bacteria were also isolated in laboratory analyses, the most commonly isolated bacterium in both the control group and the respiratory disorders group being Streptococcus equi subsp. zooepidemicus. It was isolated in 21% of tracheal aspirate from the control group and 33% of those from horses with respiratory disorders. In conclusion, N. semolina is not a primary pathogenic bacterium, as it was isolated at similar frequencies in horses with respiratory disorders and those in the healthy control group.

The involvement of glycosaminoglycans in airway disease associated with cystic fibrosis.

Individuals with cystic fibrosis (CF) present with severe airway destruction and extensive bronchiectasis. It has been assumed that these structural airway changes have occurred secondary to infection and inflammation, but recent studies suggest that glycosaminoglycan (GAG) remodelling may be an important independent parallel process. Evidence is accumulating that not only the concentration, but also sulphation of GAGs is markedly increased in CF bronchial cells and tissues. Increased expression of GAGs and, in particular, heparan sulphate, has been linked to a sustained inflammatory response and neutrophil recruitment to the CF airways. This present review discusses the biological role of GAGs in the lung, as well as their involvement in CF respiratory disease, and their potential as therapeutic targets.