Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.

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Circulating hematopoietic progenitor cells (CPCs) may be triggered by physical exercise and/or normobaric hypoxia from the bone marrow. The aim of the study was to investigate the influence of physical exercise and normobaric hypoxia on CPC number and functionality in the peripheral blood as well as the involvement of oxidative stress parameters as possibly active agents. Ten healthy male subjects (25.3±4.4 years) underwent a standardized cycle incremental exercise test protocol (40 W+20 W/min) under either normoxic (FiO2 ∼0.21) or hypoxic conditions (FiO2<0.15, equals 3,500 m, 3 h xposure) within a time span of at least 1 week. Blood was drawn from the cubital vein before and 10, 30, 60, and 120 min after exercise. The number of CPCs in the peripheral blood was analyzed by flow cytometry (CD34/CD45-positive cells). The functionality of cells present was addressed by secondary colony-forming unit-granulocyte macrophage (CFU-GM) assays. To determine a possible correlation between the mobilization of CPCs and reactive oxygen species, parameters for oxidative stress such as malondialdehyde (MDA) and myeloperoxidase (MPO) were obtained. Data showed a significant increase of CPC release under normoxic as well as hypoxic conditions after 10 min of recovery (P<0.01). Most interestingly, although CD34+/CD45dim cells increased in number, the proliferative capacity of CPCs decreased significantly 10 min after cessation of exercise (P<0.05). A positive correlation between CPCs and MDA/MPO levels turned out to be significant for both normoxic and hypoxic conditions (P<0.05/P<0.01). Hypoxia did not provoke an additional effect. Although the CPC frequency increased, the functionality of CPCs decreased significantly after exercise, possibly due to the influence of increased oxidative stress levels.

This study sought to determine whether the bone loss in untreated chronic obstructive pulmonary disease (COPD) is associated with hypercapnia and/or respiratory acidosis. Bone mineral density (BMD) measured at the distal forearm of the nondominant arm (with peripheral quantitative computed tomography [pQCT]) and serum markers of bone turnover were determined in 71 male patients with untreated COPD and 40 healthy male subjects who matched the patients in age, weight, and body mass index (BMI). The COPD patients, compared with controls, had reduced pulmonary functions, lower arterial pH, and elevated arterial partial pressure of CO 2 (P CO 2 ). The BMD (in T score) was significantly lower in COPD patients than that in control subjects (؊1.628 ؎ 0.168 vs. ؊0.058 ؎ 0.157; p < 0.001). The BMD of COPD patients correlated positively with arterial pH (r ‫؍‬ 0.582; p < 0.001), negatively with P CO 2 (r ‫؍‬ ؊0.442; p < 0.001), and negatively with serum cross-linked telopeptide of type I collagen (ICTP), a bone resorption marker (r ‫؍‬ ؊0.444; p < 0.001) but not with serum osteocalcin, a bone formation marker. Serum ICTP, but not osteocalcin, correlated with P CO 2 (r ‫؍‬ 0.593; p < 0.001) and arterial pH (r ‫؍‬ ؊0.415; p < 0.001). To assess the role of hypercapnia, COPD patients were divided into the hypercapnic (P CO 2 > 45 mm Hg; n ‫؍‬ 35) and eucapnic (P CO 2 ‫؍‬ 35-45 mm Hg) group (n ‫؍‬ 36). Patients with hypercapnia had lower BMD, lower arterial pH, and higher serum ICTP than did patients with eucapnia. Arterial pH and serum ICTP of eucapnic patients were not different from those of controls. To evaluate the role of uncompensated respiratory acidosis, COPD patients with hypercapnia were subdivided into those with compensatory respiratory acidosis (pH > 7.35; n ‫؍‬ 20) and those with uncompensated respiratory acidosis (pH < 7.35; n ‫؍‬ 15). The BMD and serum ICTP were not different among the two subgroups. In conclusion, this study presents the first associative evidence that the bone loss in COPD is at least in part attributed to an increased bone resorption that is associated primarily with hypercapnia rather than uncompensated respiratory acidosis. (J Bone Miner Res 2001;16:2132-2141)

A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported.