Ali Kocabas

Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study

Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study. 14 sites recruited population-based samples of adults aged ≥40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data. Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV1/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV1 either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV1/FEV6 ratio in place of the FEV1/FVC yielded similar prevalence estimates. Use of the FEV1/FVC<LLN criterion instead of the FEV1/FVC <0.7 should minimise known age biases and better reflect clinically significant irreversible airflow limitation. Our study also supports the use of the FEV1/FEV6 as a practical substitute for the FEV1/FVC.

Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty—a BOLD analysis

Background Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). Methods National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. Results National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US

Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project

15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US

Oxidant-antioxidant balance in patients with COPD.

15 000. Conclusions Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries.

The oxidant-antioxidant balance in mild asthmatic patients.

Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35–1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37–0.67), level of education completed (OR 0.76, 95% CI 0.67–0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42–3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05–1.47), tuberculosis (OR 1.78, 95%CI 1.17–2.72) and a family history of COPD (OR 1.50, 95% CI 1.19–1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.

Restricted spirometry in the Burden of Lung Disease Study.

The goal of this study was to evaluate the role of oxidant–antioxidant balance in the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female; mean age (yr) ± SD: 62.4 ± 9.3], 30 healthy smokers [27 male, 3 female; mean age (yr) ± SD: 58.7 ± 6.0], 71 patients with stable COPD [68 male, 3 female; mean age (yr) ± SD: 63.5 ± 7.9], and 31 patients with COPD exacerbation [30 male, 1 female; mean age (yr) ± SD: 64.2 ± 7.3]. In all study groups the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation (1048.2 ± 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers (947.9 ± 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity in healthy smokers and patients with stable COPD was higher than in healthy nonsmokers, the difference was not statistically significant. We found that healthy smokers and stable and exacerbated COPD patients had an impairment in oxidant–antioxidant balance. We suggested that new therapeutic interventions, which may repair the impaired oxidant-antioxidant balance in COPD, are needed to prevent the development of COPD.

Specificity of MOC-31 and HBME-1 immunohistochemistry in the differential diagnosis of adenocarcinoma and malignant mesothelioma: a study on environmental malignant mesothelioma cases from Turkish villages

We investigated the oxidant-antioxidant balance and the effect of inhaled corticosteroids on this balance in mild stable asthmatics. Included in the study were 30 mild asthmatic patients (11 male, 19 female, mean age (year) ± SD: 35.1 ± 9.7) and 26 healthy adults (7 male, 19 female, mean age (year) ± SD: 40.8 ± 13.3). In all study groups, the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was lower in the asthmatic group (5.7 ± 1.2 nmol/ml) than in the healthy group (6.3 ± 1.7 nmol/ml); and the mean erythrocyte SOD level was higher in asthmatic group (1086.4 ± 247.4 U/gHb) than in the healthy group (1028.0 ± 230.0 U/gHb). However, there were no significant differences in measurements of both plasma MDA levels and erythrocyte SOD enzyme activities between the groups (respectively, p = 0.1 and p = 0.4). When asthmatic patients were divided into subgroups as “inhaled steroid user” and “no inhaled steroid user”, no significant differences were observed in the measurements of either plasma MDA level or erythrocyte SOD enzyme activity between the mentioned subgroups. According to the results of our study, we can say that oxidant-antioxidant balance is not significantly affected in mild asthmatics or measurement of plasma level of MDA and erythrocyte SOD enzyme activity is not sensitive to the oxidant-antioxidant balance in mild asthmatics.

Chlamydophila Pneumoniae Infection in Adult Asthmatics Patients

Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with Stage III-B and IV non-small cell lung cancer

Histological diagnosis of malignant mesothelioma (MM) and differentiation from adenocarcinoma is often difficult. A number of clinical, radiologic, histologic and histochemical criteria have been used as diagnostic aids, but most cases cannot be readily classified on the basis of these characteristics. In recent years, a panel of immunohistochemical antibodies have been increasingly applied for the differential diagnosis of these two tumors. MOC-31 has been recently used as specific for adenocarcinomas while reacting with a minimal number of benign and malignant mesothelial proliferations, and HBME-1 has also been presented as a mesothelial cell marker. In this study, we aimed to show the importance of these two antibodies among the environmental MM cases from Southeastern Turkey. Fifty five cases of MM and twenty adenocarcinomas were included in this study. Histochemical (PAS, PAS-D, mucicarmine) and immunohistochemical (Keratin, EMA, CEA, MOC-31, HBME-1) stains have been performed on each case. Keratin was positive in all cases. EMA stained 50 of 55 MM and all the adenocarcinoma cases. According to our results, dPAS, mucicarmen, CEA and MOC-31 positivity was statistically significant in the diagnosis of adenocarcinoma whereas HBME-1 was demonstrable in most MM cases (52/55) and 11 adenocarcinoma cases. —This study confirmed that in the diagnostic distinction between MM and adenocarcinoma, immunohistochemistry is an important diagnostic tool, however, a panel of antibodies must be used rather than any single antibody. HBME-1 should be included in this panel; MOC-31 can be used where CEA is not available or to doublecheck the reactivity of this antibody.

The effect of different treatment modalities on oxidative stress in COPD

Objectives: This study has attempted to investigate the prevalence of Chlamydophila pneumoniae (CP) infection in patients with asthma. Methods: A total of 84 patients with stable asthma (58 males + 26 females; mean age ± SD; 37.3 ± 11.0 years), 22 patients with asthma exacerbation (17 males + 5 females; mean age ± SD; 33.2 ± 9.1 years), and 34 healthy adults (18 males + 16 females; mean age ± SD; 30.4 ± 11.5 years) were included in the study. Serum and throat wash samples were obtained from all patients and healthy controls 2 times, 1 month apart. Micro Immuno Fluorescence method for detecting CP antibodies in serum, and polymerase chain reaction (PCR) method for detecting presence of CP infection in the throat wash samples were used. Results: The frequency of PCR positivity for CP in throat wash samples was higher in the patients with stable asthma (28.6%) than in healthy control group (11.8%) (p < 0.01). However no significant difference was found between healthy control group and asthma exacerbated group (22.7%) (p > 0.05). In addition, seroprevalences of acute and chronic CP infections were not different between patient and control groups (p > 0.05). Serological acute infection for CP was not detected among patients with positive PCR results. In contrast, although not statistically significant, serologically chronic infection for CP was detected in 3 (60%) of 5 patients with asthma exacerbation, in 18 (75%) of 24 patients with stable asthma, and 2 (50%) of 4 with healthy controls (p > 0.05). Conclusion: CP infection detected by the PCR method was more prevalent among patients with stable asthma and chronic/persistant CP infection might have an important role in asthma pathogenesis.