Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.

https://www.medicinejournal.co.uk/article/S1357-3039(06)00582-2/pdf

Chronic obstructive pulmonary disease.

Background/Objective 
The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection.
Methodology/Main Results 
We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

/pdf/electronic-cigarette-liquid-increases-inflammation-and-virus-6idi67v2lz.pdf

Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation that persists after smoking cessation This inflammation is heterogeneous but the key inflammatory cell types involved are macrophages, neutrophils and T cells Other lung cells may also produce inflammatory mediators, particularly the epithelial cells The main inflammatory mediators include tumor necrosis factor alpha, interleukin-1, interleukin-6, reactive oxygen species and proteases COPD is also associated with systemic inflammation and there is a markedly increased risk of cardiovascular disease (particularly coronary artery disease) and lung cancer in patients with COPD There is strong associative evidence that the inflammatory cells/mediators in COPD are also relevant to the development of cardiovascular disease and lung cancer There are a large number of potential inhibitors of inflammation in COPD that may well have beneficial effects for these comorbidities This is a not well-understood area and there is a requirement for more definitive clinical and mechanistic studies to define the relationship between the inflammatory process of COPD and cardiovascular disease and lung cancer

/pdf/inflammation-in-chronic-obstructive-pulmonary-disease-and-2pa8d2jrbs.pdf

Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer

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.

https://www.dovepress.com/getfile.php?fileID=38752

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

Chronic obstructive pulmonary disease (COPD) has been associated with a nihilistic attitude. On the basis of current evidence, this nihilistic attitude is totally unjustified. The disease must be viewed through the lens of a new paradigm: one that accepts COPD as not only a pulmonary disease but also as one with important measurable systemic consequences. COPD is not only preventable but also treatable. Smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have all been shown to impact on mortality. In addition, pulmonary rehabilitation, pharmacologic therapy, and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, exercise capacity, and even exacerbations and hospitalizations. Caregivers should familiarize themselves with the multiple complementary forms of treatment and individualize therapy to the particular situation of each patient. The f...

Chronic Obstructive Pulmonary Disease

Rationale: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.

Objectives: To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.

Methods: We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.

Measurements and Main Results: COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms−1; P = 0.025). Arterial stiffness rose by an average of 1.2 ms−1 (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms−1; P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L, P = 0.003; N-terminal pro–brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).

Conclusions: Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

/pdf/cardiovascular-risk-myocardial-injury-and-exacerbations-of-446ln046ai.pdf

Cardiovascular Risk, Myocardial Injury, and Exacerbations of Chronic Obstructive Pulmonary Disease

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.

https://erj.ersjournals.com/content/erj/44/1/87.full.pdf

Human rhinovirus infection during naturally occurring COPD exacerbations

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition of the lung caused by an abnormal response to particles and noxious gases, primarily cigarette smoke. Patients suffer daily symptoms and can have episodes of worsening symptoms termed acute exacerbations. Exacerbations are associated with impaired quality of life, faster lung function decline, higher mortality and increased risk of hospitalisation. The aetiology of COPD exacerbations is controversial; however respiratory viral and bacterial infections are an important feature of exacerbations. This study utilised real-time qPCR to measure prevalence and load of human rhinovirus (HRV) in stable COPD and during the time-course of naturally occurring exacerbations and their recovery. HRV was assessed in association with upper respiratory tract (URT) symptoms namely cold symptoms and sore throats, secondary bacterial infection, patient reported outcomes and exacerbation frequency. Additionally, respiratory syncytial virus (RSV) was semi-quantitatively examined in stable COPD and at exacerbation. The original contribution of this work to the field is that HRV prevalence and load are highest at exacerbation presentation and decrease during recovery. HRV load is higher in the presence of URT symptoms compared to the load without, and the load remains higher for longer with both symptoms compared to only one. This study described novel evidence for the development of secondary bacterial infection after HRV infection in natural exacerbations, and demonstrated that HRV infection is associated with patient reported outcomes. Patients with HRV had higher exacerbation frequencies compared to those without HRV. RSV prevalence did not change significantly between stable COPD and exacerbation. The findings from this thesis have important implications in terms of exacerbation therapy. The evidence provided may allow appropriate targeting of therapeutic interventions therefore reducing exacerbation severity and frequency. These findings emphasise the importance of rapid development of therapeutic targets for the prevention and treatment of HRV infection in COPD patients.

Human Rhinovirus at Naturally Occurring COPD Exacerbation

Arterial stiffness, a validated measure of cardiovascular risk, increases from stable COPD to exacerbation (Patel et al, ERS 2011). We hypothesised this increased cardiovascular risk was mediated by airway infection. We measured aortic pulse wave velocity (aPWV) in the stable state, at exacerbation and during recovery at 3,7,14 and 35days thereafter. Infective exacerbations were defined by a potentially pathogenic microbe (PPM) in exacerbation sputum by culture or positive PCR for H. influenzae, S. pneumoniae, M. catarrhalis , or human rhinovirus. Differences in the area under the curve (AUC) adjusted for stable aPWV level between groups were compared by unpaired t-test. 55 COPD patients (32 male, 11 current smokers) had a mean±SD FEV 1 of 1.14±0.41L (46.7±18.5%predicted) and FEV 1 /FVC ratio 0.46±0.14. Two-thirds of them (36/55, 65%) produced a sputum sample at exacerbation. Two-thirds of these events (24/36, 67%) had an identifiable PPM. Patients with an infective exacerbation had a greater rise in arterial stiffness from stable state to exacerbation (1.4±1.7ms-1 vs 0.4±1.0ms-1, p=0.050). Arterial stiffness was also higher during the recovery period in those with an infective exacerbation (AUC 37.4±55.2ms-1days vs 11.4±44.3ms-1days, p=0.036). The increase in arterial stiffness during COPD exacerbations appears to be driven by airway infection and may explain the association between these infective events and increased cardiovascular risk.

https://erj.ersjournals.com/content/erj/40/Suppl_56/4295.full.pdf

SN George

Papers

Cardiovascular Risk, Myocardial Injury, and Exacerbations of Chronic Obstructive Pulmonary Disease

Human rhinovirus infection during naturally occurring COPD exacerbations

Human Rhinovirus at Naturally Occurring COPD Exacerbation

The impact of airway infection on cardiovascular risk during COPD exacerbations