Short term dynamics of the sputum microbiome among COPD patients

Sinha, Rohita; Weissenburger-Moser, Lisa; Clarke, Jennifer; Smith, Lynette M.; Heires, Art J.; Romberger, Debra J.; LeVan, Tricia D.

doi:10.1371/journal.pone.0191499

Cited by 16 publications

(12 citation statements)

References 32 publications

(62 reference statements)

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“…This suggests that bacterial infection at exacerbation may be a key driver of the frequent exacerbator phenotype rather than viruses and that, as exacerbation frequency increases, a higher proportion of events in an individual is likely to be bacterially related. This effect was not seen at stable state, which is possibly indicative of a relatively constant microbiome, as reported previously in clinically stable COPD patients [10, 15]. In terms of viral infections, these are deemed to be stochastic events that occur following transmission and are identified less frequently than bacterial infection during an exacerbation [16].…”

Section: Discussionsupporting

confidence: 60%

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort

et al. 2019

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The association between exacerbation aetiology and exacerbation frequency is poorly understood.We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years.The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p<0.01). This was not seen with other infection types or eosinophilic inflammation.Analysis of the same cohort over 2 years showed, for the first time, that changes in yearly COPD exacerbation rate may be associated with variations in H. influenzae colonisation.

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Section: Discussionsupporting

confidence: 60%

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort

et al. 2019

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“…There are few longitudinal studies examining the change of the lung microbiome over time. Most of the studies examine microbiome differences between exacerbations and stable state [44][45][46]. There is only one study [44] examining the microbiome dynamics in clinically stable COPD patients (Stage 2), which shows a stable composition in the microbiome in the short-term (2 days period), in contrast to an increasing variability in the long-term re-assessment (9 month period).…”

Section: Microbiome Heterogeinity and Diversity In Stable Copdmentioning

confidence: 99%

The lung microbiome dynamics between stability and exacerbation in chronic obstructive pulmonary disease (COPD): Current perspectives

Dima

Kyriakoudi

Kaponi

et al. 2019

Respiratory Medicine

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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with a course that is not uniform for all COPD patients. Although smoking is considered as the major cause of the disease, persistent or recurrent infections seem to play a particular role in the disease establishment and progression. COPD is characterized by dysregulated immunity that has been associated with the bacterial colonization and infections.The establishment of culture-independent techniques has shed new light on the relationships between bacterial ecology and health status and expanded our knowledge on the lung microbiome. Interactions between the host and lung microbiome result in inflammation and activation of resident cells. The lung microbiome contains populations of symbionts and pathobionts in balance which lose their equilibrium and disturb the balance of Thelper and regulatory T-cells (Treg) upon infection, or lung disease. In COPD factors such as disease severity, exacerbations, degree of inflammation, and type of treatment used (e.g inhaled or systemic steroids and antibiotics) affect the composition of lung microbiota. Recent data indicate that the presence of specific bacterial taxa in the airways has the potential to influence the host immune response and possibly to interfere with disease phenotype. Although, there is a growing body of evidence for the role of microbiome in COPD several unanswered questions still exist for its clinical relevance.

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“…Sinha et al collected repeated induced sputum samples from four stable patients ith COPD over 9 months. They reported the stability of bacterial composition and diversity over 2 days, with increased variability over 9 months 78. In a larger longitudinal cohort (n=101), Mayhew et al found relative stability in microbial composition in a participant subset,51 while those with more variability were more likely to have higher exacerbation frequency.…”

Section: Introductionmentioning

confidence: 99%

Sputum microbiome profiling in COPD: beyond singular pathogen detection

Ditz

Christenson

Rossen

et al. 2020

Thorax

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Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question ‘who is there?’ Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions ‘what can they do?’ and ‘what are they doing?’ This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives.

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Short term dynamics of the sputum microbiome among COPD patients

Cited by 16 publications

References 32 publications

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort

Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort

The lung microbiome dynamics between stability and exacerbation in chronic obstructive pulmonary disease (COPD): Current perspectives

Sputum microbiome profiling in COPD: beyond singular pathogen detection

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