scholarly journals Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza

2021 ◽  
Author(s):  
Alejandra Hernández-Terán ◽  
Angel E. Vega-Sánchez ◽  
Fidencio Mejía-Nepomuceno ◽  
Ricardo Serna-Muñoz ◽  
Sebastián Rodríguez-Llamazares ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Microbial Communities ◽  
Antibiotic Treatment ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Pathogenic Bacteria ◽  
Microbial Community Composition ◽  
Upper Respiratory Tract ◽  
Probability Of Survival

AbstractSeveral factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered), use of antibiotics, and different days of symptoms onset differ in their microbial community composition. We found striking differences in the diversity and composition of the microbiota depending on the days of symptoms onset and with mortality of the studied patients. We detected a high abundance of opportunistic pathogens such as Enterococcus, Granulicatella, and Staphylococcus in patients either deceased or with antibiotic treatment. Also, we found that antibiotic treatment deeply perturbs the microbial communities in the LRT and affect the probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could, in turn, generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

ACUTE RESPIRATORY DISEASE IN INFANCY AND CHILDHOOD: PRESENT UNDERSTANDING AND PROSPECTS FOR PREVENTION

PEDIATRICS ◽  
1965 ◽  
Vol 36 (1) ◽  
pp. 21-39
Author(s):  
Robert M. Chanock ◽  
Robert H. Parrott
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Lower Respiratory Tract ◽  
Pathogenic Bacteria ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Acute Respiratory Disease ◽  
Infancy And Childhood ◽  
Tract Disease

DURING the past ten years there has been an exponential increase in our understanding of the etiology and epidemiology of acute respiratory disease. Unfortunately development of the means for control of these illnesses has not kept pace with etiologic or epidemiologic understanding. In this presentation an attempt will he made to summarize the role of a number of viruses and mycoplasmas in acute respiratory disease of infancy and childhood. In addition the ecology of such infections will be discussed, particularly those aspects of infection which have relevance to the problem of immunoprophylaxis. Much of the information to be discussed is derived from studies at the Children's Hospital of D.C. and the Junior Village Welfare Nursery of D.C. In many instances similar findings have been reported from other localities so that the conclusions which can be drawn from the Washington, D.C., studies would appear to have more than local significance. Since the Washington D.C., studies represent the longest continuous inquiry into the nature of acute pediatric respiratory disease primary emphasis will be placed on the interpretation of these findings. Bacteria Although group A beta hemolytic streptococci play an important role in upper respiratory tract disease it would appear that these organisms are relatively unimportant in the more serious types of illness in which lower respiratory tract involvement occurs. The careful studies of Babe, Beem, and co-workers indicate that pathogenic bacteria are not important primary etiologic agents in lower respiratory tract disease of infancy and childhood. For this reason major emphasis in this presentation will be given to the role of viruses and mycoplasmas in respiratory disease.

scholarly journals The Role of the Immune Response in the Pathogenesis of Bronchiectasis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Paul T. King
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Therapeutic Potential ◽  
Small Airways ◽  
Upper Respiratory Tract ◽  
Causative Factors ◽  
Triggering Factor

Bronchiectasis is a prevalent respiratory condition characterised by permanent and abnormal dilation of the lung airways (bronchi). There are a large variety of causative factors that have been identified for bronchiectasis; all of these compromise the function of the immune response to fight infection. A triggering factor may lead to the establishment of chronic infection in the lower respiratory tract. The bacteria responsible for the lower respiratory tract infection are usually found as commensals in the upper respiratory tract microbiome. The consequent inflammatory response to infection is largely responsible for the pathology of this condition. Both innate and adaptive immune responses are activated. The literature has highlighted the central role of neutrophils in the pathogenesis of bronchiectasis. Proteases produced in the lung by the inflammatory response damage the airways and lead to the pathological dilation that is the pathognomonic feature of bronchiectasis. The small airways demonstrate infiltration with lymphoid follicles that may contribute to localised small airway obstruction. Despite aggressive treatment, most patients will have persistent disease. Manipulating the immune response in bronchiectasis may potentially have therapeutic potential.

scholarly journals Topography of the respiratory tract bacterial microbiota in cattle

2020 ◽  
Author(s):  
Christopher McMullen ◽  
Trevor W. Alexander ◽  
Renaud Léguillette ◽  
Matthew Workentine ◽  
Edouard Timsit
Keyword(s):  
Respiratory Tract ◽  
Pathogenic Bacteria ◽  
Primary Source ◽  
Alpha Diversity ◽  
Sampling Location ◽  
Rrna Gene ◽  
Upper Respiratory Tract ◽  
Bacterial Microbiota ◽  
Sampling Locations

Abstract Background Bacterial bronchopneumonia (BP) is the leading cause of morbidity and mortality in cattle. While the bacterial composition of the bovine upper respiratory tract (URT) has not been studied in detail, the nasopharynx is generally accepted as the primary source of pathogenic bacteria that cause BP. However, it has recently been shown in humans that the oropharynx may act as the primary reservoir for pathogens that reach the lung. The objective was therefore to describe the bacterial microbiota present along the entire cattle respiratory tract to determine which URT niches may contribute the most to the composition of the lung microbiota. Methods Seventeen upper and lower respiratory tract locations were sampled from 15 healthy feedlot steer calves. Samples were collected using a combination of swabs, protected specimen brushes, and saline washes. DNA was extracted from each sample and the 16S rRNA gene (V3-V4) was sequenced. Community composition, alpha-diversity, and beta-diversity were compared among sampling locations. Results Microbiota composition differed across sampling locations, with physiologically and anatomically distinct locations showing different relative abundances of 1,137 observed sequence variants (SVs). An analysis of similarities showed that the lung was more similar to the nasopharynx (R-statistic = 0.091) than it was to the oropharynx (R-statistic = 0.709) or any other URT sampling location. Five distinct metacommunities were identified across all samples after clustering at the genus level using Dirichlet multinomial mixtures. This included a metacommunity found primarily in the lung and nasopharynx that was dominated by Mycoplasma . Further clustering at the SV level showed a shared metacommunity between the lung and nasopharynx that was dominated by Mycoplasma dispar . Other metacommunities found in the nostrils, tonsils, and oral microbiotas were dominated by Moraxella , Fusobacterium , and Streptococcus , respectively. Conclusions The nasopharyngeal bacterial microbiota is most similar to the lung bacterial microbiota and therefore may serve as the primary source of bacteria to the lung. This finding confirms that the nasopharyngeal microbiota should be the focus of research as it relates to the role of the URT microbiota in BP. As well, this microbiota should be the main target for future interventions and pharmaceuticals aimed at controlling and preventing BP.

scholarly journals Influenza A Virus Reassortment Is Limited by Anatomical Compartmentalization following Coinfection via Distinct Routes

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Mathilde Richard ◽  
Sander Herfst ◽  
Hui Tao ◽  
Nathan T. Jacobs ◽  
Anice C. Lowen
Keyword(s):  
Respiratory Tract ◽  
Influenza A Virus ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Upper Respiratory Tract ◽  
Extrinsic Factors ◽  
Genetic Incompatibility ◽  
Viral Spread ◽  
Virus Reassortment ◽  
The Impact

ABSTRACTExchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.IMPORTANCEGenetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.

scholarly journals Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Karen Ivinson ◽  
Georgia Deliyannis ◽  
Leanne McNabb ◽  
Lara Grollo ◽  
Brad Gilbertson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Lethal Dose ◽  
Laboratory Mouse ◽  
Influenza Virus Infection ◽  
Upper Respiratory Tract ◽  
Upper Respiratory

ABSTRACT It is possible to model the progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages. The factors that govern the progression of virus down the respiratory tract are not well understood. Here, we show that, while PR8 virus grows to high titers in the nose, an inhibitor present in the saliva blocks further progression of infection to the trachea and lungs and renders an otherwise lethal dose of virus completely asymptomatic. In vitro, the salivary inhibitor was capable of potent neutralization of PR8 virus and an additional 20 strains of type A virus and two type B strains that were tested. The exceptions were Udorn virus and the closely related H3N2 strains A/Port Chalmers/1/73 and A/Victoria/3/75. Characterization of the salivary inhibitor showed it to be independent of sialic acid and other carbohydrates for its function. This and other biochemical properties, together with its virus strain specificity and in vivo function, indicate that the mouse salivary inhibitor is a previously undescribed innate inhibitory molecule that may have evolved to provide pulmonary protection of the species from fatal influenza virus infection. IMPORTANCE Influenza A virus occasionally jumps from aquatic birds, its natural host, into mammals to cause outbreaks of varying severity, including pandemics in humans. Despite the laboratory mouse being used as a model to study influenza virus pathogenesis, natural outbreaks of influenza have not been reported in the species. Here, we shed light on one mechanism that might allow mice to be protected from influenza in the wild. We show that virus deposited in the mouse upper respiratory tract will not progress to the lower respiratory tract due to the presence of a potent inhibitor of the virus in saliva. Containing inhibitor-sensitive virus to the upper respiratory tract renders an otherwise lethal infection subclinical. This knowledge sheds light on how natural inhibitors may have evolved to improve survival in this species.

scholarly journals 425. The Utility of Paired Upper and Lower COVID-19 Sampling in Patients with Artificial Airways

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S279-S279
Author(s):  
Eimear Kitt ◽  
Julia S Sammons ◽  
Kathleen Chiotos ◽  
Susan E Coffin ◽  
Susan E Coffin ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Diagnostic Testing ◽  
Cross Sectional Study ◽  
Upper Respiratory Tract ◽  
Cross Sectional ◽  
Mechanically Ventilated ◽  
Paired Samples ◽  
Control And Prevention ◽  
Polymerase Chain

Abstract Background The Centers for Disease Control and Prevention (CDC) recommends upper respiratory tract (URT) polymerase chain reaction (PCR) testing as the initial diagnostic test for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Lower respiratory tract (LRT) testing for patients requiring mechanical ventilation is also recommended. The goal of this study was to evaluate concordance between paired URT and LRT specimens in children undergoing pre-admission/procedure screening or diagnostic testing. We hypothesized that < 10% of paired tests would have discordant results. Methods Single center cross-sectional study including children with artificial airways who had paired URT and LRT SARS-CoV-2 PCR testing between 4/1/2020 and 6/8/2020. URT specimens included nasopharyngeal (NP) swabs and aspirates. LRT specimens included tracheal aspirates and bronchoalveolar lavages. URT and LRT specimens were classified as paired if the two specimens were collected within 24 hours. Artificial airways included tracheostomies and endotracheal tubes. Tests were classified as diagnostic versus screening based on the indication selected in the order. Results 102 paired specimens were obtained during the study period. Fifty-nine were performed for screening and 43 were performed for diagnosis of suspected SARS-CoV-2. Overall, 94 specimens (92%) were concordant, including 89 negative from both sources and 5 positive from both sources. Eight specimens (8%) were discordant, all of which were positive from the URT and negative from the LRT (Figure 1). Among patients undergoing screening, 3 of 4 positive tests were discordant and among symptomatic patients, 5 of 9 positive tests were discordant. There were no instances of a positive LRT specimen with a negative URT specimen. Figure 1. Performance of upper and lower respiratory tract SARS-CoV-2 PCR testing in children with artificial airways Conclusion Overall, most paired samples from the URT and LRT yielded concordant results with no pairs positive from the LRT and negative from the URT. These data support the CDC recommendation that URT specimens are the preferred initial SARS-CoV-2 test, while LRT specimens should be collected only from mechanically ventilated with suspected SARS-CoV-2. Disclosures All Authors: No reported disclosures

scholarly journals The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sung-Yoon Kang ◽  
Hyojung Kim ◽  
Sungwon Jung ◽  
Sang Min Lee ◽  
Sang Pyo Lee
Keyword(s):  
Principal Component Analysis ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Beta Diversity ◽  
Lower Respiratory Tract ◽  
Principal Component ◽  
Control Group ◽  
Flexible Bronchoscope ◽  
Bronchial Washing

Abstract Background The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. Results Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. Conclusions The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.

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