Lung microbiology and exacerbations in COPD

Beasley, Victoria; Joshi, Priya V; Singanayagam, Aran; Molyneaux, Philip L.; Johnston, Sebastian L.; Mallia, Patrick

doi:10.2147/copd.s28286

Cited by 91 publications

(53 citation statements)

References 141 publications

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“…Indeed, emphysema-like lung on CT has recently been shown to be associated with respiratory exacerbations and hospitalizations among smokers independent of the FEV 1 (52). Other mechanisms linking emphysema to all-cause mortality include increased susceptibility to pulmonary infections (53), impaired cardiac function (54) resulting in reduced cardiopulmonary reserve, and systemic inflammation (55). …”

Section: Discussionmentioning

confidence: 99%

Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction

Oelsner¹,

Hoffman²,

Folsom

et al. 2014

Ann Intern Med

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Background Whereas low lung function is known to predict mortality in the general population, the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) remains uncertain. Objective To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons without airflow obstruction or COPD in the general population. Design Prospective cohort study. Setting Population-based, multiethnic sample from 6 US communities. Participants 2965 participants ages 45-84 years without airflow obstruction on spirometry. Measurements Emphysema-like lung was defined on cardiac CT as the number of lung voxels less than -950 Hounsfield Units, and was adjusted for the number of total imaged lung voxels. Results Among 2965 participants, 50.9% of whom never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio [HR]1.14 per one-half of the interquartile range, 95% CI 1.04-1.24, P=0.004), adjusting for potential confounders including cardiovascular risk factors and the forced expiratory volume in one second. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status. Limitations Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses. Conclusions Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted. Primary Funding Source NIH/NHLBI.

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Section: Discussionmentioning

confidence: 99%

Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction

Oelsner¹,

Hoffman²,

Folsom

et al. 2014

Ann Intern Med

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“…Treatment selection might also consider how the microbiology may differ in patients with severe exacerbations versus patients with mild or moderate disease 79. The most common pathogens isolated from sputum and bronchoscopic samples are Haemophilus influenzae, Streptococcus pneumoniae , and Moraxella catarrhalis .…”

Section: What Are the Recommended Treatment Strategies For Severe Copmentioning

confidence: 99%

“…The most common pathogens isolated from sputum and bronchoscopic samples are Haemophilus influenzae, Streptococcus pneumoniae , and Moraxella catarrhalis . However, in patients with more severe disease and/or exacerbations, Gram-negative pathogens, such as Pseudomonas aeruginosa , are common,79,80 and may prove more challenging to treat in light of increasing resistance in some regions. The role of procalcitonin as a potential biomarker for optimizing antibiotic-treatment strategy in COPD exacerbations (especially those induced by bacterial infection) is also being investigated; however, as yet its role is unproven 81,82.…”

Section: What Are the Recommended Treatment Strategies For Severe Copmentioning

confidence: 99%

Impact and prevention of severe exacerbations of COPD: a review of the evidence

Halpin¹,

Miravitlles²,

Metzdorf³

et al. 2017

COPD

185

159

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Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management.

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“…Of note, COPD exacerbations are most commonly triggered by bacterial or viral respiratory infections (8–10). Hypercapnia is also an independent risk factor for mortality in hospitalized patients with community-acquired pneumonia (11, 12), children with lower respiratory tract adenovirus infection (13), and cystic fibrosis patients awaiting lung transplantation (3).…”

Section: Introductionmentioning

confidence: 99%

Hypercapnia Inhibits Autophagy and Bacterial Killing in Human Macrophages by Increasing Expression of Bcl-2 and Bcl-xL

Casalino‐Matsuda

Nair

Beitel

et al. 2015

The Journal of Immunology

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Hypercapnia, the elevation of CO2 in blood and tissue, commonly develops in patients with advanced lung disease and severe pulmonary infections, and is associated with high mortality. We previously reported that hypercapnia alters expression of host defense genes, inhibits phagocytosis, and increases the mortality of Pseudomonas pneumonia in mice. However, the effect of hypercapnia on autophagy, a conserved process by which cells sequester and degrade proteins and damaged organelles that also plays a key role in antimicrobial host defense and pathogen clearance, has not previously been examined. In the present study we show that hypercapnia inhibits autophagy induced by starvation, rapamycin, LPS, heat-killed and live bacteria in the human macrophage. Inhibition of autophagy by elevated CO2 was not attributable to acidosis. Hypercapnia also reduced macrophage killing of Pseudomonas aeruginosa. Moreover, elevated CO2 induced the expression of Bcl-2 and Bcl-xL, anti-apoptotic factors that negatively regulate autophagy by blocking Beclin 1, an essential component of the autophagy initiation complex. Furthermore, siRNA targeting Bcl-2 and Bcl-xL and the small molecule Z36, which blocks Bcl-2 and Bcl-xL binding to Beclin 1, prevented hypercapnic inhibition of autophagy and bacterial killing. These results suggest that targeting the Bcl-2/Bcl-xL-Beclin 1 interaction may hold promise for ameliorating hypercapnia-induced immunosuppression and improving resistance to infection in patients with advanced lung disease and hypercapnia.

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Lung microbiology and exacerbations in COPD

Cited by 91 publications

References 141 publications

Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction

Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction

Impact and prevention of severe exacerbations of COPD: a review of the evidence

Hypercapnia Inhibits Autophagy and Bacterial Killing in Human Macrophages by Increasing Expression of Bcl-2 and Bcl-xL

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