Comparative Assessment of Outcomes in Drug Treatment for Smoking Cessation and Role of Genetic Polymorphisms of Human Nicotinic Acetylcholine Receptor Subunits.

Objective: To investigate the effects of genetic polymorphisms of human nicotinic acetylcholine receptor subunits α3, α4 and α5, which are encoded by CHRNA3, CHRNA4 CHRNA5 genes, respectively, on nicotine addiction and outcomes of pharmacological treatments for smoking cessation. Methods: A total of 143 smokers and 130 non-smokers were included. Genotyping for CHRNA3 rs578776, CHRNA4 rs1044396-rs1044397, CNRNA5 rs16969968 polymorphisms was performed by PCR, flowed by RFLP. Clinical outcomes and success rates of pharmacological treatments for smoking cessation with nicotine replacement therapy (NRT), bupropion or varenicline were determined at the 12th week of the treatment. Results: Overall, 52 out of 143 (36.4%) smokers who received pharmacotherapy were able to quit smoking. Success rates for smoking cessation were similar for female (30.3%) and male (41.6%) subjects (p = 0.16). The success rate for smoking cessation treatment with varenicline (58.5%) was significantly higher as compared to other treatments with NRT (20.0%), bupropion (32.3%) or bupropion + NRT (40.0%) (chi-square test, p = 0.001). Smoker vs. non-smoker status and the clinical outcomes of drugs used for smoking cessation were found similar in subjects carrying wild-type and variant alleles of human nicotinic acetylcholine receptor α subunits. Conclusion: In this study, smoking cessation treatment with varenicline was significantly more effective than treatments with nicotine replacement or bupropion in a cohort of Turkish subjects. Smoker/non-smoker status and the clinical outcomes of treatment with pharmacological agents were similar in subjects with wild-type or variant alleles for human nicotinic acetylcholine receptor subunits α3 (CHRNA3), α4 (CHRNA4) and α5 (CHRNA5).

Is there any contribution of bronchial washing to biopsy in the diagnosis of patients with endobronchial pathology in the era of personalized medicine?

INTRODUCTION: Bronchoscopic biopsies and bronchial washings (BW) are commonly used together for the diagnosis of centrally located tumors. This study aimed to investigate the clinical relevance of routinely collecting BWs in patients who simultaneously had biopsies for visible endobronchial lesions in the current molecular analysis-driven personalized medicine era. MATERIALS AND METHODS: We retrospectively reviewed the patients who underwent fiberoptic bronchoscopy (FOB) between October 2011 and December 2016. Patients who had both BW and biopsy specimens (EBB: endobronchial forceps biopsy and/or EBNA: endobronchial needle aspiration biopsy) for visible endobronchial lesions were included in this study. Demographic and clinical data, macroscopic findings during FOB, pathology results, and final diagnoses were collected from the hospital database. RESULT: The study included 269 patients (220 males/49 females) with a mean age of 61.6 ± 10.6 years. While the overall diagnostic yield of FOB was 71.4%, the diagnostic yields of bronchoscopic procedures were 68.2% for EBB, 83.3% for EBNA, and 19.7% for BW. Only three patients (1.1%) with undiagnostic biopsies had positive BW cytology revealing merely malignant epithelial cells. CONCLUSIONS: BW provided a negligible diagnostic contribution in 1.1% (n= 3) of the patients. These three patients had undergone further diagnostic procedures for making a proper therapeutic management plan. In the era of personalized therapy, it is logical to obtain more biopsy in the time spent for BWs.

Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/ or venous thrombosis accompanied by persistently elevated levels of antiphospholipid antibodies (aPLs). The aim of this study is to evaluate the pulmonary manifestations of APS and compare the levels of aPLs in patients with and without pulmonary involvement. We retrospectively reviewed the files of patients with the diagnosis of APS between October 2010 and May 2017. Demographic data, clinical, radiological and laboratory findings were recorded. The study included 67 patients (56 female/11 male) with a mean age of 39 ± 13 years. Pulmonary manifestations such as parenchymal and/or vascular involvement were seen in 12 (17.9%) patients. The patients with and without pulmonary manifestations were not significantly different in terms of age (p = 0.46), comorbidities (p = 0.48) and APS duration (p = 0.66). Acute pulmonary thromboembolism (PE) was determined in 11 (16.4%), alveolar hemorrhage in 2 (3%) patients. Four patients with acute PE (36%) developed chronic thromboembolic pulmonary hypertension (CTEPH). One patient developed both CTEPH and diffuse alveolar hemorrhage after acute PE during follow up. Antiphosholipid antibody IgM was highly positive in patients with PE compared to patients without PE (p = 0.005). Other antibodies and lupus anticoagulant were not significantly different in patients with and without PE. None of the patients were deceased due to pulmonary manifestations of APS. PE was the most common pulmonary manifestation of APS. The development of CTEPH was high among APS patients. Patients with APS should be closely followed for the onset of PE and CTEPH.

Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation.

OBJECTIVES: To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. METHODS: 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. RESULTS: Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). CONCLUSION: Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

The contribution of bronchoalveolar lavage in the diagnosis of welder's lung in a patient with pulmonary fibrosis.

Interstitial pulmonary fibrosis is rare clinical entity related to welding usually associated with long term and heavy exposure to welding fumes. A 56-year-old asymptomatic male patient was referred to our clinic due to abnormal chest X-ray findings that was requested for regular controls. He has been working as a welder both indoor and outdoor settings for the last 25 years. The radiological findings were compatible with usual interstitial pneumonia on computed tomography of thorax. Pulmonary function tests, exercise capacity and laboratory results were within normal limits. Collagen tissue markers were negative. In order to confirm the relation of welding with pulmonary fibrosis, bronchoalveolar lavage was performed and stained with Prussian blue. The demonstration of hemosiderin-laden macrophages (25%) confirmed this association and allowed differential diagnosis. Besides it helped the patient decide to leave his job.

The Relationship between Hypomagnesemia and Pulmonary Function Tests in Patients with Chronic Asthma.

OBJECTIVE: To investigate the relationship between serum values of magnesium and the parameters of the pulmonary function tests (PFT) in patients with chronic asthma. SUBJECTS AND METHODS: This study recruited 50 patients with chronic stable asthma and 40 healthy individuals as a control group. Data on age, sex, severity of asthma, PFT, and details of drug therapy were obtained from each group. Serum magnesium, potassium, phosphorus, calcium, and sodium levels were also measured. To evaluate differences between groups, the Student t test or Mann-Whitney U test was performed for continuous variables, and the χ2 test for categorical variables. RESULTS: In the asthma group, 10% (n = 9) of the patients had hypomagnesemia and 5.5% (n = 5) had hypophosphatemia. Patients with asthma were divided into two groups: the hypomagnesemic group (n = 9) and the normomagnesemic group (n = 41). Forced expiratory volume in 1 s (FEV1), FEV1%, peak expiratory flow (PEF), and PEF% were lower in the hypomagnesemic group than in the normomagnesemic group (p = 0.02). Multiple logistic regression analysis revealed a statistically significant association between hypomagnesemia and PFT in the hypomagnesemic asthmatic group. The correlations of age with FEV1, FEV1%, PEF, and PEF% were as follows: p = 0.00, r = 0.29; p = 0.00, r = 0.43; p = 0.03, r = 0.22; p = 0.00, r = 0.38; and p = 0.03, r = 0.22, respectively. The correlation of serum magnesium levels with PFT (FEV1, FEV1%, PEF, PEF%) were as follows: p = 0.001, r = 0.29; p = 0.001, r = 0.43; p = 0.03, r = 0.22; and p = 0.001, r = 0.38, respectively. The other electrolytes were within the normal range in both groups. CONCLUSION: In this study, hypomagnesemia and hypophosphatemia were found to be the most common electrolyte abnormalities in patients with chronic stable asthma. FEV1, FEV1%, PEF, and PEF% were significantly lower in asthmatic patients with hypomagnesemia compared to asthmatic patients with normomagnesemia.

Diagnostic utility of conventional transbronchial needle aspiration in older patients.

BACKGROUND: In older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients aged ≥ 65 years. METHOD: We retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients aged ≥ 65 years and in younger patients were determined. RESULTS: C-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3 ± 4.6 and 52.5 ± 10 years, respectively (p < 0.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (p = 0.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (n = 1) and bronchospasm (n = 3). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (p = 0.49). CONCLUSION: C-TBNA is a safe procedure with similar diagnostic yield in older patients.

Acute massive pulmonary embolism associated with olanzapine.

Treatment with low-potency anti-psychotic agents is an important risk factor in the development of pulmonary embolism (PE). We report a case of 74years old female patient receiving olanzapine for psychotic depression admitted to the emergency service with the complaints of chest pain and shortness of breath. She had tachypnea, hypotension and tachycardia. Arterial blood gas analysis showed hypoxemia-hypocapnia and D-dimer level was high. Computed tomographic pulmonary angiography (CTPA) demonstrated pulmonary embolism in both main pulmonary arteries, through lobar and segmental branches. Tissue plasminogen activator (t-PA) was administered in intensive care unit. As the only possible risk factor for PE was olanzapine, olanzapine treatment was terminated with pyschiatry consultation. During the 12-month follow-up of the patient; malignancy was not observed. Diagnosis and prevention of PE are the important goals to reduce morbidity and mortality in subjects receiving olanzapine.

Exhaled carbon monoxide is a marker of heavy nicotine dependence.

BACKGROUND/AIM: Exhaled CO level provides an objective measure of a patient's smoking status. The relationship between CO levels and nicotine dependence is controversial. The aim of this study is to evaluate the relationship between exhaled CO levels and nicotine dependence as well as to demonstrate that exhaled CO levels may be used as a marker of nicotine dependence. MATERIALS AND METHODS: Two hundred eighty-nine patients (132 females, 157 males) were included in the study. Smoking duration, the age of smoking initiation, exhaled CO levels, and Fagerström Test for Nicotine Dependence (FTND) scores were recorded. The relationship between FTND scores and exhaled CO levels was investigated. RESULTS: There was a statistically significant correlation between FTND score and exhaled CO levels (P < 0.001). We found that a cut-off score of 7.5 ppm for exhaled CO may be useful as a marker for heavy smoking. The sensitivity and specificity of this cut-off score for exhaled CO was 69.3% and 49.3%, respectively (P < 0.001). CONCLUSION: We found that exhaled CO levels significantly correlated with FTND scores. For patients who are unable to provide reliable answers to questions in the FTND, exhaled CO measurements may be used as an alternative test for estimating the status of heavy smoking.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders. However, the utility of EBUS-TBNA in the diagnosis of mediastinal lymphomas is unclear. The aim of this study was to determine the diagnostic value of EBUS-TBNA in patients with suspected lymphoma. MATERIALS AND METHODS: Sixty-eight patients with isolated mediastinal lymphadenopathy and suspected of lymphoma were included in the study. EBUS-TBNA was performed on outpatients under moderate sedation. The sensitivity, specificity, negative predictive value and diagnostic accuracy of EBUS-TBNA were calculated. RESULTS: Sixty-four patients were diagnosed by EBUS-TBNA, but four patients with non-diagnostic EBUS-TBNA required surgical procedures. Thirty-five (51.5%) patients had sarcoidosis, six (8.8%) had reactive lymphadenopathy, nine (13.3%) had tuberculosis, one (1.5%) had squamous cell carcinoma, two (2.9%) had sarcoma and fifteen (22%) had lymphoma (follicular center cell, large B-cell primary, and Hodgkin lymphomas in three, two, and ten, respectively). Of the 15 lymphoma patients, thirteen were diagnosed by EBUS and two by thoracotomy and mediastinoscopy. The sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma were calculated as 86.7%, 100%, 96.4%, and 97%, respectively. CONCLUSIONS: EBUS-TBNA can be employed in the diagnosis of mediastinal lymphoma, instead of more invasive surgical procedures.

Rapid diagnosis of mediastinal tuberculosis with polymerase chain reaction evaluation of aspirated material taken by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic method for tuberculosis (TB). This study was conducted to determine the efficiency of polymerase chain reaction (PCR) testing for detecting TB lymphadenitis in samples obtained by EBUS-TBNA. MATERIALS AND METHODS: A total of 93 consecutive patients with hilar/mediastinal lymphadenopathies and diagnosed with granulomatous diseases through histopathological evaluation were included in the study. The specimens provided by EBUS-TBNA were evaluated through pathological, microbiological, and molecular tests. RESULTS: Eighty-nine (95.7%) of the 93 patients had histopathologically granulomatous diseases by EBUS-TBNA. Tuberculosis was diagnosed in 27 (30.3%) patients and sarcoidosis was diagnosed in 62 (69.7%) patients. Four (4.3%) patients were diagnosed through mediastinoscopy. Endobronchial ultrasound-guided transbronchial needle aspiration had an overall diagnostic efficiency in TB of 96.9%, a sensitivity of 90.9%, and a specificity of 100%. Mycobacterium tuberculosis PCR was positive in 17 of the 30 patients. The sensitivity of PCR was 56.7%, the specificity was 100%, and the general efficiency of the test was 96.4%. CONCLUSIONS: As a result, the use of M. tuberculosis PCR in the EBUS-TBNA specimens provides a rapid and an accurate diagnosis of TB. Therefore, we recommend the use of M. tuberculosis PCR in the EBUS-TBNA specimens as a rapid diagnostic method for mediastinal lymphadenopathies in patients with suspected TB.

Importance of biomarkers in risk stratification of pulmonary thromboembolism patients.

INTRODUCTION: Patients with pulmonary thromboembolism (PTE) are classified into 3 groups according to the clinical risk factors associated with mortality. High-risk patients and some of the intermediate-risk patients should be treated immediately to decrease the high mortality risk. Although clinical risk level of PTE can be determined by using echocardiography to evaluate right ventricle overload and pulmonary artery pressure findings, it may not be available in all emergency settings. AIM: The purpose of the study was to define the laboratory biomarkers, which can be used in place of echocardiography for PTE risk stratification. METHODS: Patients (n = 98) were divided into 3 groups as high-risk (n = 13), intermediate-risk (n = 50), and low-risk (n = 35) groups, according to clinical risk factors at the first referral to hospital. Hepatic, cardiac, and renal markers were evaluated and compared among 3 groups. RESULTS: Among biomarkers examined, lactate dehydrogenase, urea, creatinine, uric acid, troponin I, N-terminal-pro-B-type natriuretic peptide, creatine kinase-MB, D-dimer, and erythrocyte sedimentation rate (ESR) levels were found different between groups. All of these biomarkers except for ESR had positive correlation, whereas ESR had negative correlation with the mortality risk. An analysis of covariance for the age difference among patient groups showed that all the biomarkers other than urea and D-dimer levels remained significantly different among risk groups. CONCLUSIONS: At emergency conditions in which echocardiography assessment is not available, PTE patients who have increased levels of certain hepatic, cardiac, and renal biomarkers should cautiously be evaluated for having an increased risk for mortality. Increased levels of these biomarkers may guide the consideration for thrombolytic treatment.

Diagnostic imaging of pulmonary embolism using endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a new technique that can be used for the diagnostic imaging of central pulmonary thromboembolism (PE). In eight cases at our clinic, EBUS was used because of mediastinal lymphadenopathies or paramediastinal nodular lesions and at the same time images were obtained of a PE by means of EBUS. The PE was diagnosed before the EBUS with computed tomography (CT) of the lungs in all cases (5 women and 3 men). The repletion defects of all the cases compatible with a PE were clarified with CT-angiography. EBUS may be an alternative method for the diagnosis of PE, as it can indicate the presence of a thrombus in the central pulmonary arteries in hemodynamically-stable cases.

ACE gene deletion/deletion polymorphism may be a protective factor for respiratory distress in preterm infants.

The objective in this study was to evaluate the angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism in premature infants with and without respiratory distress within the first 24 hours of life. Totally, 87 premature babies who were followed up in the neonatal unit were included in the study. Of these babies, 41 had respiratory distress, and constituted the patient group. The remaining 46 babies who did not have respiratory distress constituted the control group. Blood samples were obtained from the babies within the first few days of life prior to administration of any blood product. The ACE gene insertion (I) and deletion (D) polymorphism was investigated using polymerase chain reaction method. The I/I polymorphism was frequent in the patient group and the D/D polymorphism was frequent in the control group (p < 0.05). There was no relationship between the ACE gene polymorphism and hospital stay, ventilation or oxygen consumption duration of the patients. In addition, taking into consideration the gestational age, no association was found between ACE gene polymorphism and birth weights of the babies. The I/I genotype was considered a risk factor for pulmonary disorders in neonates as the I/I variant was more frequent in the neonates with respiratory distress than in healthy newborns. The ACE I/I genotype is associated with an increased risk of respiratory disorders among premature infants and the D/D genotype is a protective factor for respiratory disorders, but these infants with ACE D/D genotype might be at risk for the development of cardiovascular disorders later in life.