Oxidative stress has been implicated in the pathogenesis and progression of COPD. Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden. Structural changes to essential components of the lung are caused by oxidative stress, contributing to irreversible damage of both parenchyma and airway walls. The antioxidant N-acetylcysteine (NAC), a glutathione precursor, has been applied in these patients to reduce symptoms, exacerbations, and the accelerated lung function decline. This article reviews the available experimental and clinical data on the antioxidative effects of NAC in COPD, with emphasis on the role of exhaled biomarkers.

ObjectiveThe 12-item Partners in Health scale (PIH) was developed in Australia to measure self-management behaviour and knowledge in patients with chronic diseases, and has undergone several changes. Our aim was to assess the construct validity and reliability of the latest PIH version in Dutch COPD patients.MethodsThe 12 items of the PIH, scored on a self-rated 9-point Likert scale, are used to calculate total and subscale scores (knowledge; coping; recognition and management of symptoms; and adherence to treatment). We used forward-backward translation of the latest version of the Australian PIH to define a Dutch PIH (PIH(Du)). Mokken Scale Analysis and common Factor Analysis were performed on data from a Dutch COPD sample to investigate the psychometric properties of the Dutch PIH; and to determine whether the four-subscale solution previously found for the original Australian PIH could be replicated for the Dutch PIH.ResultsTwo subscales were found for the Dutch PIH data (n = 118); 1) knowledge and coping; 2) recognition and management of symptoms, adherence to treatment. The correlation between the two Dutch subscales was 0.43. The lower-bound of the reliability of the total scale equalled 0.84. Factor analysis indicated that the first two factors explained a larger percentage of common variance (39.4% and 19.9%) than could be expected when using random data (17.5% and 15.1%).ConclusionWe recommend using two PIH subscale scores when assessing self-management in Dutch COPD patients. Our results did not support the four-subscale structure as previously reported for the original Australian PIH.

We investigated the sensitivity and reproducibility of a test procedure for measuring hydrogen peroxide (H202) in exhaled breath condensate and the effect of storage of the condensate on the H2O2 concentration, and compared the results to previous studies. Twenty stable COPD patients breathed into our collecting device twice for a period of 10 min. The total exhaled air volume (EAV) and condensate volume were measured both times and the H2O2 concentration of the condensate was determined fluorimetrically. The concentration was measured again after freezing the reaction product at -70 degrees C for a period of 10, 20 and 40 days. We collected 2-5 ml condensate in 10 min. The EAV and condensate volumes were strongly correlated. There was no significant difference between the mean H2O2 concentration of the first and second test. We obtained a detect on limit for the H2O2 concentration of 0.02 micromoll(-1). The H2O2 concentration appeared to remain stable for a period up to 40 days of freezing. Compared to previous studies we developed a more efficient breath condensate collecting device and obtained a lower H2O2 detection limit. The measurement of exhaled H2O2 was reproducible. In addition, storage of the samples up to 40 days showed no changes in H2O2 concentration.

Background: Because inflammation induces oxidative stress, exhaled hydrogen peroxide (H₂O₂), which is a marker of oxidative stress, may be used as a non-invasive marker of airway inflammation in chronic obstructive pulmonary disease (COPD). There are no data on the circadian variability of exhaled H₂O₂ in COPD patients. Objective: The aim of this study was to investigate the variability of the H₂O₂ concentration in breath condensate of stable COPD patients and of matched healthy control subjects. Methods: We included 20 patients with stable mild COPD (forced expiratory volume in 1 s ∼70% of predicted) and 20 healthy subjects, matched for age, sex and pack-years, all smokers or ex-smokers. Breath condensate was collected and its H₂O₂ concentration determined fluorometrically three times on day 0 (9 and 12 a.m., and 3 p.m.) and once on days 1, 2, 3, 8 and 21. Results: The mean H₂O₂ concentration increased significantly during the day in both the patient and control groups (p = 0.02 and p < 0.01, respectively). Over a longer period up to 21 days, the mean concentration did not change in both groups. There was no significant difference between patients and controls. The mean coefficient of variation over 21 days was 45% in the patient group and 43% in the control group (p = 0.8). Conclusions: The exhaled H₂O₂ concentration increased significantly during the day in both stable COPD patients and controls. Over a period of 3 weeks, the mean H₂O₂ concentration did not change and the variability within the subjects was similar in both groups.

Background: The effects of inhaled corticosteroids (ICS) on markers of oxidative stress in patients with stable COPD are unclear. Objectives: The aim was to investigate the effect of ICS on exhaled H₂O₂ in stable COPD patients and to compare ICS with different lung deposition. Methods: Forty-one stable patients with moderate COPD (FEV₁ ∼60% predicted) were randomized to sequence 1; first HFA-134a beclomethasone dipropionate (HFA-BDP, an ICS with more peripheral deposition) 400 µg b.i.d., then fluticasone propionate (FP, an ICS with more central deposition) 375 µg b.i.d. (n = 20) or sequence 2 ; first FP, then HFA-BDP (n = 21). Both 4-week treatment periods were preceded by a 4-week washout period. After each period, the concentration of H₂O₂ in exhaled breath condensate was measured. Results: The H₂O₂ concentration decreased significantly after the first treatment period in both sequence 1 and 2 (p < 0.05, p = 0.01, respectively). In neither sequence was there a return to baseline values after the second washout, indicating a carry-over effect. The concentrations remained low in both sequences during the second treatment period. Conclusions: Both ICS appeared to reduce exhaled H₂O₂ in stable COPD patients. However, this study showed no difference between ICS with different deposition patterns, which in part may be due to the carry-over effect.

Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of COPD, partly because of the release of oxidants, like superoxide anion (SA). The goal of this study was to measure the spontaneous and stimulated release of SA by peripheral PMN in stable COPD compared with healthy controls. Seventeen patients with stable moderate COPD and 17 healthy age-matched controls were included. SA release from peripheral PMN was measured spectrophotometrically as the superoxide dismutase (SOD) inhibitable reduction of cytochrome c. PMNs were stimulated with phorbol myristate acetate (PMA, 1 and 10 ng/ml), diesel exhaust particles (DEPs), carbon black (CB) and ultrafine CB (ufCB, 125, 250 and 500 microg/ml). The spontaneous SA release (PMA-0) between patients and control subjects was not significantly different. After stimulation with PMA, SA release increased in both patients and controls. The SA release did not increase after stimulation with DEP and CB in patients nor in controls. There was only an increase after stimulation with ufCB in the patient group. The increased SA release in COPD patients after stimulation with ufCB may suggest that PMN of COPD patients are more prone to stimulation and that the smaller particle size of ufCB might be a crucial factor.

BackgroundPoor adherence to inhaled medications in COPD patients seems to be associated with an increased risk of death and hospitalization. Knowing the determinants of nonadherence to inhaled medications is important for creating interventions to improve adherence.ObjectivesTo identify disease-specific and health-related quality of life (HRQoL) factors, associated with adherence to inhaled corticosteroids (ICS) and tiotropium in COPD patients.MethodsAdherence of 795 patients was recorded over 3 years and was deemed optimal at >75%–≤125%, suboptimal at ≥50%–<75%, and poor at <50% (underuse) or >125% (overuse). Health-related quality of life was measured with the Clinical COPD Questionnaire and the EuroQol-5D questionnaire.ResultsPatients with a higher forced expiratory volume in 1 second (FEV1)/vital capacity (VC) (odds ratio [OR] =1.03) and ≥1 hospitalizations in the year prior to inclusion in this study (OR =2.67) had an increased risk of suboptimal adherence to ICS instead of optimal adherence. An increased risk of underuse was predicted by a higher FEV1/VC (OR =1.05). Predictors for the risk of overuse were a lower FEV1 (OR =0.49), higher scores on Clinical COPD Questionnaire-question 3 (anxiety for dyspnea) (OR =1.26), and current smoking (OR =1.73). Regarding tiotropium, predictors for suboptimal use were a higher FEV1/VC (OR =1.03) and the inability to perform usual activities as asked by the EuroQol-5D questionnaire (OR =3.09). A higher FEV1/VC also was a predictor for the risk of underuse compared to optimal adherence (OR =1.03). The risk of overuse increased again with higher scores on Clinical COPD Questionnaire-question 3 (OR =1.46).ConclusionSeveral disease-specific and quality of life factors are related to ICS and tiotropium adherence, but a clear profile of a nonadherent patient cannot yet be outlined. Overusers of ICS and tiotropium experience more anxiety.

Background: Lung cancer is the most common neoplasm in Turkey, but there is not enough data on the characteristics of this mortal illness in our country. Objectives and Methods: The Turkish Thoracic Society, Lung and Pleural Malignancies Study Group (TTS-LPMSG) conducted a national retrospective hospital-based study to determine the pattern of lung cancer in Turkey. Results: A total of 11,849 lung cancer patients were studied between 1994 and 1998, 90.4% were male and 9.6% were female. The majority of patients were smokers (77.9%) or ex-smokers (10.8%). The mean age at the time of diagnosis was 58.4 years (20–84) and 56.7% of the patients were aged between 46 and 65 years. The most common histological types were squamous cell (45.4%), small cell (SCLC; 20.5%) and adenocarcinoma (20.2%). The majority of patients with non-small-cell lung cancer were diagnosed with metastatic disease (40.4%). Of the patients with SCLC patients, 37.9% had limited stage disease and 62.7% extensive stage disease at diagnosis. Conclusion: The results of the largest data so far collected in Turkey show that the vast majority of patients with lung cancer are male, squamous cell is the most common histological type, and only a small proportion of patients are diagnosed at an early stage.