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Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

ABSTRACT: The lungs of people and companion animals are now recognized to harbor diverse, low biomass bacterial communities. While these communities are difficult to characterize using culture-based approaches, targeted molecular methods such as 16S rRNA amplicon sequencing can do so using DNA extracted from samples such as bronchoalveolar lavage fluid (BALF). Previous studies identified a surprisingly uniform composition of the microbiota in the lungs of healthy research dogs living in a controlled environment, however there are no reports of the lung microbiota of client-owned dogs. Moreover, compositional changes in the lung microbiota depending on disease status have been reported in people, suggesting that similar events may occur in dogs, a species subject to several respiratory disease mechanisms analogous to those seen in people. To address these knowledge gaps, BALF samples from client-owned dogs presenting to the University of Missouri Veterinary Health Center for respiratory signs between 2014 and 2017 were processed for and subjected to 16S rRNA sequencing. Based on specific diagnostic criteria, dogs were categorized as Chronic Bronchitis (CB, n = 53) or non-CB (n = 11). Community structure was compared between groups, as well as to historical data from healthy research dogs (n = 16) of a uniform breed and environment. The lung microbiota detected in all client-owned dogs was markedly different in composition from that previously detected in research dogs and contained increased relative abundance of multiple canine fecal and environmental bacteria, likely due to aspiration associated with their clinical signs. While inter-sample diversity differed significantly between samples from CB and non-CB dogs, the variability within both groups made it difficult to discern reproducible bacterial classifiers of disease. During subsequent analyses to identify other sources of variability within the data however, population-wide temporal dynamics in community structure were observed, with substantial changes occurring in late 2015 and again in early 2017. A review of regional climate data indicated that the first change occurred during a historically warm and wet period, suggesting that changes in environmental conditions may be associated with changes in the respiratory microbiota in the context of respiratory disease. As the lung microbiota in humans and other animals is believed to result from repetitive micro-aspirations during health and in certain disease states associated with dyspnea and laryngeal dysfunction, these data support the increased colonization of the lower airways during compromised airway function, and the potential for temporal effects due to putative factors such as climate.

SUBMITTER: Ericsson AC

PROVIDER: S-EPMC6986754 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

Ericsson Aaron C AC Personett Alexa R AR Rindt Hansjorg H Grobman Megan E ME Reinero Carol R CR

PloS one 20200128 1

The lungs of people and companion animals are now recognized to harbor diverse, low biomass bacterial communities. While these communities are difficult to characterize using culture-based approaches, targeted molecular methods such as 16S rRNA amplicon sequencing can do so using DNA extracted from samples such as bronchoalveolar lavage fluid (BALF). Previous studies identified a surprisingly uniform composition of the microbiota in the lungs of healthy research dogs living in a controlled envir ...[more]

PMID: 31990924

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Project description:ImportanceChronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain.ObjectiveTo assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers.Design, setting, and participantsThis prospective cohort study included 22?325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018.ExposuresNonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years.Main outcomes and measuresLung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis.ResultsAmong 22?325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11?082 ever smokers with 99?869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11?243 never smokers with 120?004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes.Conclusions and relevanceThe findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

Project description:ObjectivesWhile feline chronic bronchitis (CB) is known as neutrophilic bronchial inflammation (NI), feline asthma (FA) is defined as an eosinophilic airway inflammation (EI). Feline chronic bronchial disease refers to both syndromes, with similar clinical presentations and applied treatment strategies. Recent studies described alterations of the microbiota composition in cats with FA, but little is known about the comparison of the lung microbiota between different types of feline bronchial disease. The study aimed to describe the bacterial microbiota of the lower respiratory tracts of cats with FA and CB and to identify potential differences.MethodsTwenty-two client-owned cats with FA (n = 15) or CB (n = 7) confirmed via bronchoalveolar-lavage (BALF)-cytology were included. Next-generation sequencing analysis of 16S rRNA genes was performed on bacterial DNA derived from BALF samples. QIIME was used to compare microbial composition and diversity between groups.ResultsEvenness and alpha-diversity-indices did not significantly differ between cats with FA and CB (Shannon p = 0.084, Chao 1 p = 0.698, observed ASVs p = 0.944). Based on a PERMANOVA analysis, no significant differences were observed in microbial composition between animals of both groups (Bray-Curtis metric, R-value 0.086, p = 0.785; unweighted UniFrac metric, R-value -0.089, p = 0.799; weighted Unifrac metric, R-value -0.072, p = 0.823). Regarding taxonomic composition, significant differences were detected for Actinobacteria on the phylum level (p = 0.026), Mycoplasma spp. (p = 0.048), and Acinetobacteria (p = 0.049) on the genus level between cats with FA and CB, with generally strong interindividual differences seen. There was a significant difference in the duration of clinical signs before diagnosis in animals dominated by Bacteriodetes (median 12 months, range 2-58 months) compared to animals dominated by Proteobacteria (median 1 month, range 1 day to 18 months; p = 0.003).Conclusions and relevanceLung microbiota composition is very similar in cat populations with spontaneous FA and CB besides small differences in some bacterial groups. However, with disease progression, the lung microbiome of cats with both diseases appears to shift away from dominantly Proteobacteria to a pattern more dominated by Bacteriodetes. A substantial proportion of cats tested positive for Mycoplasma spp. via sequencing, while none of them tested positive using classical PCR.

Project description:BackgroundChronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores.MethodsThis study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB.ResultsAmong the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB.ConclusionsCB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Project description:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has posed multiple challenges to global public health. Clinical features and sequela of SARS-CoV-2 infection include long-term and short-term complications often clinically indistinguishable from bacterial sepsis and acute lung infection. Post-hoc studies of previous SARS outbreaks postulate secondary bacterial infections with microbial dysbiosis. Oral microbial dysbiosis, particularly the altered proportion of Firmicutes and Proteobacteria, observed in other respiratory virus infection, like influenza, has shown to be associated with increased morbidity and mortality. Oropharynx and lung share similar kinds of bacterial species. We hypothesized that alteration in the Human Oropharyngeal Microbiome in SARS-CoV-2 patients can be a clinical indicator of bacterial infection related complications. We made a longitudinal comparison of oropharyngeal microbiome of 20 SARS-CoV-2 patients over a period of 30 days; at three time points, with a 15 days interval; contrasting them with a matched group of 10 healthy controls. Present observation indicates that posterior segment of the oropharyngeal microbiome is a key reservoir for bacteria causing pneumonia and chronic lung infection on SARS-CoV-2 infection. Oropharyngeal microbiome is indeed altered and its α-diversity decreases, indicating reduced stability, in all SARS-CoV-2 positive individuals right at Day-1; i.e. within ~24 h of post clinical diagnosis. The dysbiosis persists long-term (30 days) irrespective of viral clearance and/or administration of antibiotics. There is a severe depletion of commensal bacteria phyla like Firmicutes among the patients and that depletion is compensated by higher proportion of bacteria associated with sepsis and severe lung infection from phyla Proteobacteria. We also found elevated proportions of certain genus that have previously been shown to be causal for lung pneumonia in studies of model organisms and human autopsies' including Stenotrophomonas, Acenetobactor, Enterobactor, Klebsiella and Chryseobacterium that were to be elevated among the cases. We also show that responses to the antibiotics (Azithromycin and Doxycycline) are not uniform for all individuals.

Dataset Information

Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

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Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

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