Could the Sputum Microbiota Be a Biomarker That Predicts Mortality after Acute Exacerbations of Chronic Obstructive Pulmonary Disease?
Ontology highlight
ABSTRACT:
SUBMITTER: Tsay JJ
PROVIDER: S-EPMC6519852 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Could the Sputum Microbiota Be a Biomarker That Predicts Mortality after Acute Exacerbations of Chronic Obstructive Pulmonary Disease?
Tsay Jun-Chieh J JJ Segal Leopoldo N LN
American journal of respiratory and critical care medicine 20190501 10
Similar Datasets
Project description:Frequent acute exacerbations are the leading cause of high rates of hospitalization and mortality in chronic obstructive pulmonary disease (COPD). Despite the enormous worldwide medical burden, reliable molecular markers for effective early diagnosis and prognosis of acute exacerbations are still lacking. Both the host genetics and airway microbiome are known to play potential roles in the pathogenesis of frequent exacerbations. Here, we performed whole exome sequencing (WES) and 16S rRNA gene sequencing to explore the interaction between these two factors and their implications in the pathogenesis of frequent exacerbations. We collected peripheral blood (n = 82), sputum samples (n = 59) and clinical data from 50 frequent-exacerbation phenotype (FE) COPD patients and 32 infrequent-exacerbation phenotype (IE) as controls. Based on filtering the deleterious sites, candidate mutated genes shared only in FE patients and did not occur in the IE group were identified. Microbiota analysis revealed significant differences in bacterial diversity and composition between FE and IE groups. We report the underlying pathogenic gene including, AATF, HTT, CEP350, ADAMTS9, TLL2 genes, etc., and explore their possible genotypic-phenotypic correlations with microbiota dysbiosis. Importantly, we observed that AATF gene mutations were significantly negatively correlated with microbial richness and diversity. Our study indicated several deleterious mutations in candidate genes that might be associated with microbial dysbiosis and the increased risk of frequent acute exacerbations in COPD patients. These results provide novel evidence that exomes and related microbiomes may potentially serve as biomarkers for predicting frequent acute exacerbations in COPD patients.
| S-EPMC9599557 | biostudies-literature
Project description:The role of airway microbiota in COPD is highly debated. Symptomology assessment is vital for the management of clinically stable COPD patients; however, the link between symp toms and the airway microbiome is currently unknown.The present study aimed to evaluate the relationship among stable COPD patients.We conducted pyrosequencing of bacterial 16S rRNA using induced sputum samples in a Han Chinese cohort that included 40 clinically stable COPD patients and 19 healthy controls.Alterations in community composition and core bacte rial taxa (Neisseria subflava, etc.) were observed in patients with severe symptoms compared with controls. The co-occurrence network indicated that the key microbiota enriched in COPD patients showed higher expression in patients with severe symptoms. The association pattern of symptoms with the sputum microbiome was obviously different from that of lung function in COPD patients.These findings broaden our insights into the relationship between the sputum microbiota and the symptom severity in COPD patients, emphasizing the role of symptoms in the airway microbiome, independent of lung function.
| S-EPMC6072682 | biostudies-other
Project description:INTRODUCTION:Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common reason for presentation to emergency departments (ED), but the management of these episodes is often heterogeneous regardless of their potential impact on short-term adverse outcomes. METHODS:This was a longitudinal, retrospective study of all patients >40 years old admitted to the ED of two Spanish teaching hospitals for an AECOPD between January 1st and May 31st, 2016. All data were collected from electronic medical records. The primary outcomes were patient treatment at discharge and 90-day mortality. Logistic regression was used to model the determinants of 90-day mortality. RESULTS:Of the 465 included patients, 56% were prescribed a 3-drug combination at hospital discharge, 22% a 2-drug combination, 19% a single drug, and 4% other or no treatment. Approximately 8% of patients died within 90 days after an AECOPD. Multivariate logistic models revealed that having more than 2 severe exacerbations within the last 12 months (OR (95% CI): 15.12 (4.22-54.22)) and being prescribed a single drug at discharge (OR (95% CI): 7.23 (2.44-21.38)) were the main determinants of 90-day mortality after an AECOPD. CONCLUSIONS:This study reflects the real-life heterogeneity in the pharmacological treatments prescribed after an ED admission for an AECOPD and suggests the potential impact of suboptimal inhaled treatment strategies on 90-day mortality rates.
| S-EPMC6294427 | biostudies-literature
Project description:BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are debilitating events and spur disease progression. Infectious causes are frequent; however, it is unknown to what extent exacerbations are caused by larger shifts in the airways' microbiota. The aim of the current study was to analyse the changes in microbial composition between stable state and during exacerbations, and the corresponding immune response.MethodsThe study sample included 36 COPD patients examined at stable state and exacerbation from the Bergen COPD Cohort and Exacerbations studies, and one patient who delivered sputum on 13 different occasions during the three-year study period. A physician examined the patients at all time points, and sputum induction was performed by stringent protocol. Only induced sputum samples were used in the current study, not spontaneously expectorated sputum. Sputum inflammatory markers (IL-6, IL-8, IL-18, IP-10, MIG, TNF-?) and antimicrobial peptides (AMPs, i.e. LL-37/hCAP-18, SLPI) were measured in supernatants, whereas target gene sequencing (16S rRNA) was performed on corresponding cell pellets. The microbiome bioinformatics platform QIIME2TM and the statistics environment R were applied for bioinformatics analyses.ResultsLevels of IP-10, MIG, TNF-? and AMPs were significantly different between the two disease states. Of 36 sample pairs, 24 had significant differences in the 12 most abundant genera between disease states. The diversity was significantly different in several individuals, but not when data was analysed on a group level. The one patient case study showed longitudinal dynamics in microbiota unrelated to disease state.ConclusionChanges in the sputum microbiota with changing COPD disease states are common, and are accompanied by changes in inflammatory markers. However, the changes are highly individual and heterogeneous events.
| S-EPMC6748569 | biostudies-literature
Project description:Little is known about the lung microbiome dynamics and host-microbiome interactions in relation to chronic obstructive pulmonary disease (COPD) exacerbations and in patient subgroups based on smoking status and disease severity. Here we performed a 16S ribosomal RNA survey on sputum microbiome from 16 healthy and 43 COPD subjects. For COPD subjects, a longitudinal sampling was performed from stable state to exacerbations, at two and six weeks post-exacerbations and at six months from first stable visit. Host sputum transcriptome were characterized for a subset of COPD patient samples.
2021-03-21 | GSE112165 | GEO
Project description: Not available
| S-EPMC7427405 | biostudies-literature
Project description: Not available
| S-EPMC9134202 | biostudies-literature
Project description:Background and aimExacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.MethodsThis was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.ResultsOf the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.ConclusionsHospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality.
| S-EPMC4928940 | biostudies-literature
Project description:Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.
| S-EPMC2647652 | biostudies-literature
Project description:BACKGROUND: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. OBJECTIVES: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. STUDY DESIGN: case control study. METHODS: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n=13) and in control subjects (n=54) using a specific immunoassay and compared the levels using analysis of variance. RESULTS: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 +/- 120 ng/mL) compared to patients with stable disease (151 +/- 83 ng/mL) or control subjects (128 +/- 65 ng/mL; p=0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV_{1}/FVC% predicted. CONCLUSIONS: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.
| S-EPMC3834666 | biostudies-other