The lung is the organ with the highest exposure to ambient air in the entire human architecture. Due to its large surface area and blood supply, the lung is susceptible to oxidative injury in the form of myriads of reactive oxygen species (ROS) and free radicals. In order to provide defense against the oxidative burden, the lungs produce various endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/ROS, either of endogenous or environmental origin. Several mechanisms are related to the potential connection between COPD and oxidative stress. One of the most important actions of the oxidative stress is the influence of the molecular mechanisms involved in the expression proinflammatory genes. There is plenty of evidence supporting an imbalance between oxidants and antioxidants in the lung and systemic circulation of smokers and COPD patients. Detection of the oxidative burden and evaluation of their progression and phenotypes by oxidative stress biomarkers have proven challenging and difficult. Both invasive and non-invasive techniques have provided different biomarkers which contribute to the oxidative burden of the airways. An effective wide-spectrum antioxidant therapy with bioavailability is urgently needed to control the local and systemic oxidative burst in COPD. In that direction, several antioxidant agents have been evaluated as potential candidates for the management of COPD. However, despite some encouraging results, clinical trials so far have failed to elaborately define the type of antioxidant, the regimen and the time period of treatment that may improve clinically meaningful outcomes in patients with COPD.

Chronic obstructive pulmonary disease (COPD) represents a significant burden for healthcare systems that is expected to grow further in the future. Inhaled long-acting bronchodilators, including tiotropium, represent the cornerstone of management of COPD patients. Economic studies evaluating the cost-effectiveness ratio of inhaled bronchodilators have to take into account several parameters, including the reduction of COPD exacerbations and related hospitalizations, as well as disease modification and improvement in quality of life and mortality. At an era when the healthcare resources are unlikely to grow as quickly as demand, economic analyses remain the cornerstone for the justification of the broad use of medication with an acceptable cost-effectiveness ratio. The greatest importance of such studies in COPD is the identification of subgroups of patients that will have the most benefit with an acceptable cost-effectiveness ratio for the healthcare providers. The development of models that will incorporate a global evaluation of the different aspects of this multi-component disease, in order to provide the best available care to each individual patient is urgently needed.

Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.

The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.

Recently, there has been widespread interest in the use of non-invasive methods for the assessment of airway inflammation in a variety of lung diseases including chronic obstructive pulmonary disease (COPD). Sputum induction is a semi-invasive technique the value of which is not restricted to sputum cell counts, as inflammatory mediators can also be measured in the supernatants. However, none of the measurable biomarkers in induced sputum is considered applicable in clinical practice. Despite the predominating sputum neutrophilia, there is increasing evidence that the presence of sputum eosinophilia predicts an objective response to steroid treatment in patients with COPD. The commonly used Exhaled Breath Condensate (EBC) methodologies in COPD patients have considerable variability due to technical issues concerning both sample collection and analysis. Despite the above limitations, biomarkers mainly related to neutrophil derived products and oxidative stress, have been assessed for disease monitoring and response to pharmacological treatment. Endogenous airway acidification, as assessed by EBC pH, represents a measurable marker associated with oxidative stress and sputum neutrophilia. The fraction of exhaled nitric oxide (FeNO) is the most extensively studied exhaled biomarker and increased levels of FeNO have been widely documented in patients with asthma. FeNO measurement in COPD is of limited value due to smoking effect. However, increased values of FeNO have been found in COPD patients with sputum eosinophila. Moreover, measuring FeNO in different exhalation rates may reestablish its value in COPD. Despite the limited use of non-invasive methods, the future direction is a challenge towards new biomarkers or a combination of them that will assist us to move from the research laboratory to daily clinical practice.