The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. METHODS: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). RESULTS: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. CONCLUSION: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

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

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

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.

[Endobronchial capillary hemangioma: a very rare cause of massive hemoptysis]. / Masif hemoptizinin nadir bir nedeni: Endobronsiyal kapiller hemanjiyom.

Tracheal capillary hemangioma is a very rare benign tumor of trachea which may present as massive hemoptysis. Minor to massive hemoptysis can be observed in these patients. Due to its small size and tracheal localization, diagnosis cannot be easily performed by using radiological investigations. Fifty-years-old male patient who was diagnosed as tracheal capillary hemangioma with bronchoscopic biopsy was presented in this case report. According to our knowledge, this is the eighth case report in the world literature. Tracheal capillary hemangioma must be kept in mind in patients with massive hemoptysis with normal radiologic features and bronchoscopic procedures (excision, argon, laser etc.) should be the first choice of therapy when diagnosed.

COVID-19 Pandemic and the Global Perspective of Turkish Thoracic Society.

It has been more than 3 months now since the first case of COVID-19 was reported in Turkey. Globally, the number of confirmed cases and deaths reached 9,653,048 and 491,128 respectively, as reported by 216 countries by June 27, 2020. Turkey had 1,396 new cases, 194,511 total cases, and 5,065 deaths by the same date. From the first case until today, the Turkish Thoracic Society (TTS) has been very proactive in educating doctors, increasing public awareness, undertaking academic studies, and assisting with public health policies. In the present report, social, academic, and management perspectives of the pandemic are presented under appropriate subtitles. During this critical public health crisis, TTS has once again demonstrated its readiness and constructive stance by supporting public health, healthcare workers, and the environment. This review summarizes the perspective of TTS on each aspect of the COVID-19 pandemic and casts light on its contributions.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

Chlamydophila pneumoniae infection in adult asthmatics patients.

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/persistent CP infection might have an important role in asthma pathogenesis.

The evaluation of latent tuberculosis in rheumatologic diseases for anti-TNF therapy: experience with 192 patients.

It is recommended to evaluate the presence of latent tuberculosis infection (LTBI) before initiating antitumor necrosis factor alpha (anti-TNF) therapy for rheumatologic diseases. We aimed to present the follow-up results of 192 patients with rheumatologic diseases before anti-TNF therapy for LTBI. We enrolled 192 patients who were given anti-TNF therapy for their rheumatologic diseases between April 2005 and January 2008. The demographic characteristics of the patients were recorded. Chest X-ray was obtained and tuberculin skin test (TST) was performed in all patients before anti-TNF therapy. LTBI was assessed by detailed history of close contact with infectious cases within the last year, abnormal chest radiography, and positive TST (> or =5 mm) before initiating anti-TNF therapy. Patients with anti-TNF therapy were followed with 2-month intervals for active tuberculosis by pulmonary and extrapulmonary symptoms, physical examination, and chest X-ray. Of 192 patients, 104 (54.2%) patients were women, age (mean +/- SD) 43.1 +/- 12.7 years and 88 (45.8%) patients were men, age (mean +/- SD) 39.3 +/- 11.2 years. Ninety-one (47.4%) of them had rheumatoid arthritis (RA); 92 (47.9%) had ankylosing spondylitis (AS), and nine (4.7%) had psoriatic arthritis. Isoniazid treatment was started in 129 (67.2%) patients in whom LTBI was detected. No significant difference was observed for TST positivity (TST > or = 5 mm) between the patients with RA and AS (p = 0.101). Similarly, no significant difference was also observed for TST positivity between the patients who received immunosuppressive therapy and those who did not (p = 0.154). Only three (1.6%) patients developed active tuberculosis at the study period. We suggested that in despite of the presence of rheumatologic disease and/or immunosuppressive therapy, TST is an acceptable and available diagnostic test for detecting LTBI before anti-TNF therapy.

The effect of different treatment modalities on oxidative stress in COPD.

INTRODUCTION: Oxidant/antioxidant interactions are known to be important processes in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of corticosteroids (CS), and N-acetylcysteine (NAC) on plasma oxidant/antioxidant levels in patients with COPD. METHODS: This study utilised a single-blind, randomised, placebo-controlled, parallel-group methodology. We enrolled 58 patients with stable COPD and 30 healthy controls with similar demographic profiles. The patients with COPD were randomly divided into three treatment groups. Group 1 received basal treatment (regular ipratropium bromide and beta-2 agonist as needed), placebo CS and placebo NAC. In addition to basal treatment, group 2 received oral CS (methylprednisolone 40 mg/day) and placebo NAC. Group 3 received basal treatment plus NAC (600 mg/day) and placebo CS. Each group received treatment for 15 days. We measured plasma malondialdehyde (MDA) and superoxide dismutase (SOD) at the start and the end of study. RESULTS: Post-treatment plasma MDA levels were significantly lowered only in group 2 (P=0.004). No significant differences were found with respect to erythrocyte SOD levels. CONCLUSION: This study demonstrates that oral CS, by aiding the oxidant/antioxidant system, may offer a new therapeutic option in COPD treatment.

Early prediction of sarcoidosis prognosis with HLA typing: a 5 year follow-up study.

Background: A wide range of HLA-DR alleles have been associated with sarcoidosis either in terms of disease phenotype or extra pulmonary involvement, however the effect on non-resolution in different ethnic groups is not fully understood. The aim of this study was to investigate whether disease characterics and HLA-DRB1 alleles may early reflect non resolution in sarcoidosis. Methods: 91 patients who were diagnosed in Cukurova University Faculty of Medicine Department of Chest Diseases between 1993-2012 and were followed up until June 2017 were included in the study. All patients underwent HLA analysis by the Sequence Specific Oligonucleotide Prob (SSOP) method. Fifteen of them were excluded from the study group due to lost of follow-up (n=6) and not yet passed 5 years since diagnosis (n=9). Complete resolution at 5th year was defined according to the predefined standard criteria (ACCESS). Results: The resolution rate was 51.3%. The HLA-DRB1*14 allele was significantly higher in patients without resolution (11.8 vs 1.3%)(p=0.006). According to multivariate logistic regression analysis the independent risk factors of non resolution were female gender (OR: 12.6; 95%CI: 2.1-74.9, p=0.005), HLA DRB1*14 allele (OR:51.9; 95%CI: 3.6-735.8, p=0.000), baseline TLCO<75%(predicted) (OR:3.8; 95%CI: 1.1-13.7, p=0.028), extra-pulmonary involvement (OR:3.7; 95%CI: 1.0-13.1, p=0.038) and advanced stage at baseline (OR: 8.3; 95%CI: 1.9-35.4, p=0.001). Conclusions: HLA-DRB1*14 alleles, lower baseline TLCO, advanced stage, female gender or the presence of extra-pulmonary involvement could predict long term non-resolution in sarcoidosis. Early prediction of long term prognosis may affect treatment decisions and avoid further deterioration in these patient groups. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 184-191).

Isoniazid intervention for latent tuberculosis among 86 patients with rheumatologic disease administered with anti-TNFalpha.

In this study, we investigated the safety and toxicity of isoniazid (INH) intervention therapy to the patients with latent tuberculosis who were given tumor necrosis factor alpha (TNFalpha) for the treatment of their rheumatologic diseases. In this prospective clinical study, we enrolled 86 patients receiving anti-TNFalpha therapy for their rheumatologic diseases between April 2005 and September 2006. Of all the subjects, 45 had rheumatoid arthritis, 36 had ankylosing spondylitis, and 5 had psoriatic arthritis. In addition to anti-TNFalpha therapy, 60 of the 86 patients were given INH intervention for revealed latent tuberculosis. INH at a dosage of 300 mg daily was given for 9 months. Hepatotoxicity due to the INH therapy was considered when the serum alanine aminotransferase (ALT) and/or aspartate aminotransaminase (AST) levels showed at least threefold increase with respect to their baseline serum levels. Serum ALT and AST levels were measured by enzymatic colorimetric method in fasting peripheral blood samples at 0 (baseline), 1, 2, 3, 6, and 9 months. Of 86 patients, 47 (54.7%) were women (mean age+/-SD, 44.1 +/- 10.9 years) and 39 (45.3%) were men (38.8 +/- 10.1 years). Except five patients (8.3%), liver toxicity due to the INH therapy was not encountered among the patients, and after temporarily discontinuing the INH therapy of these five subjects, serum transaminase levels returned to the normal ranges. No hepatotoxicity was observed in the non-INH group. However, there was no statistical significance between INH-treated and non-INH-treated group (p = 0.317). In addition, none of the 86 patients developed active tuberculosis infection during the treatment period. In conclusion, for those patients who were assigned to the TNFalpha treatment for their rheumatologic disorders and carrying risk for latent tuberculosis, INH intervention therapy was found to be safe and efficacious.

The View of the Turkish Thoracic Society on the Report of the GOLD 2017 Global Strategy for the Diagnosis, Management, and Prevention of COPD.

Since the Global Initiative for Obstructive Lung Disease (GOLD) published its first guidelines on chronic obstructive pulmonary disease (COPD) in 2001, much has changed till 2017. Previous versions of GOLD guidelines mentioned the forced expiratory volume in one second (FEV1)-based approach for staging and treatment modalities. Since 2011, a composite multi-dimensional approach has been introduced to cover various aspects of the disease. Unfortunately, this approach was not found to be correlated with mortality as well as the FEV1-based approach, despite the fact that it was better for estimating exacerbation rates. Although this assessment tool has been considered as a big step in personalized medicine, the system was rather complex to use in daily practice. In 2017, GOLD introduced a major revision in many aspects of the disease. This mainly includes a revised assessment tool and treatment algorithm. This new ABCD algorithm has excluded spirometry for guiding pharmacological therapy. Treatment recommendations are mainly based on symptoms and exacerbation rates. Escalation and de-escalation strategies have been proposed for the first time. The spirometric measurement has only been retained to confirm the diagnosis and lead to nonpharmacological therapies. In this report, the Turkish Thoracic Society COPD assembly aimed to summarize and give an insight to the Turkish interpretation of GOLD 2017.

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.

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 anti-bodies 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, immuno-histochemistry 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.

Could HLA-DR B1*11 allele be a clue for predicting extra-pulmonary sarcoidosis?

BACKGROUND: Several HLA-DR alleles have been described as a potential risk factor for sarcoidosis between distinct ethnic groups however the relationship between HLA-DR alleles and extra-pulmonary sarcoidosis (EPS) is still scarce. OBJECTIVES: The aim of this prospective study is to investigate the relationship between extra-pulmonary involvement and HLA-DR genetic analysis in Turkish patients with sarcoidosis. METHODS: In this study, we HLA-typed sarcoidosis patients with and without extra-pulmonary involvement, and compared with healthy control subjects. The presence of EPS was evaluated with previously defined standard criteria (ACCESS) and only patients with definite and probable involvement were accepted as positive. Sequence Specific Oligonucletide Probes method was used for typing of HLA-DRB1 alleles from DNA samples in both groups. RESULTS: The frequency of HLA DRB1*15 allele was more frequent in patients with sarcoidosis than controls (% 20.4 vs % 9.6)(pcorr=0.017). According to multivariate analysis (MVA), the presence of HLA DRB1*15 was indicated as an independent risk factor for sarcoidosis (OR:2.37; 95% CI: 1.31-4.30, p=0.004). Extra-pulmonary involvement was present in 39 patients (42.9 %). When the patients with and without extra-pulmonary involvement compared, HLADRB1*11 allele was significantly higher in patients without extra-pulmonary sarcoidosis which may be concluded as a protective allele for systemic involvement (%30.8 vs. %15.4)(p<0.05). This result was also confirmed with the MVA (OR:0.35, %95 CI:0.15-0.84, p=0.018). CONCLUSIONS: We demonstrated a strong positive link between the haplotype HLA DRB1*15 and sarcoidosis in a Turkish Caucasian population and a potential protective effect of HLA DRB1*11 from extra-pulmonary involvement of disease.