Sumru Beder

Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: A crossover, placebo-controlled comparison of onset and duration of action.

Background: In contrast to the well-known activity profile in asthma, the precise efficacy and optimum dose schedules of long-acting β2-agonists in chronic obstructive pulmonary disease (COPD) are not clear. Objective: In this study, we aimed to compare the onset and the duration of action of a single inhalation of formoterol and salmeterol in COPD patients having partially reversible airway obstruction. Methods: In a double-blind, randomized, crossover and placebo-controlled study design, the respiratory functions of 22 patients (mean age 57.3 ± 5.4 years) having mild to severe COPD (5 mild, 8 moderate and 9 severe) and partially reversible airway obstruction [mean baseline reversibility of forced expiratory volume in 1 s (FEV1) 19.3 ± 3.1%] were evaluated after inhalation of 12 μg formoterol and 50 μg salmeterol. Results: Regarding the onset of bronchodilator action, the mean absolute increase of 0.20 liters in FEV1 10 min after inhalation of formoterol was significantly higher than baseline and that of placebo (0.04 liters), whereas that of salmeterol (0.11 liters) did not reach statistical significance. At 20 min, both formoterol (0.25 liters) and salmeterol (0.20 liters) produced a significant increase in FEV1 compared with baseline and with that of placebo (0.04 liters). The peak bronchodilator effects occurring at 60 and 120 min following formoterol (0.39 liters) and salmeterol (0.40 liters) inhalation, respectively, were significantly higher than the corresponding levels of placebo (0.02 and –0.12 liters, respectively). Concerning the duration of action, the 12-hour values of both formoterol (0.25 liters) and salmeterol (0.22 liters) were significantly higher than that of placebo (–0.12 liters). The area under the curve values of FEV1 of formoterol (3.5 ± 1.3 l·h) and salmeterol (3.2 ± 1.2 l·h) averaged over 12 h were comparable and higher than placebo values (1.2 ± 0.5 l·h). After formoterol inhalation 2 patients experienced tremor and 1 had palpitation; 1 tremor and 1 headache attack were noted after salmeterol. For the pharmacologically predictable side effects, there was no difference between the drugs. Conclusions: In conclusion, this study revealed that a single dose of 12 μg formoterol and 50 μg salmeterol provided comparable bronchodilation within 12 h and had tolerable side effects in patients with mild to severe COPD having partially reversible airway obstruction.

Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.

Objectives:We investigated the role of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in cachexia development in newly diagnosed nonsmall cell lung cancer (NSCLC) patients. Methods:We evaluated 44 (M/F:41/3) NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a weight loss of ≥10% consisted the cachectic group (n:23, M/F:21/2) and the ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2). Results:Body mass index (BMI) of cachectics was significantly lower than that of noncachectics (21.0 ± 2.9 versus 24.5 ± 3.6, P = 0.02) and controls (21.0 ± 2.9 versus 25.5 ± 2.6, P = 0.01). Serum TNF-α level did not differ between cachectic and noncachectics (37.3 ± 39.1 and 51.6 ± 84.2 pg/mL, respectively). However, it was significantly higher in NSCLC patients compared with controls (44.1 ± 64.3 and 15.1 ± 14.3 pg/mL, P = 0.03). Serum IL-6 level was not different between 3 groups (6.4 ± 4.1, 8.9 ± 16.3, and 4.1 ± 3.5 pg/mL, respectively) but it correlated significantly with TNF-α (r = 0.4, P = 0.006) and BMI (r = −0.3, P = 0.03). Erythrocyte sedimentation rate (ESR) correlated significantly with TNF-α (r = 0.4, P = 0.003) and BMI (r = −0.3, P = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in cachectics and noncachectics, with no statistical difference (12.2 ± 3.7 and 11.2 ± 1.0 months, respectively). Conclusions:TNF-α and IL-6 levels did not differ significantly between cachectics and noncachectics. However, significant correlations between IL-6, BMI, and TNF-α suggested that these cytokines acted as cofactors in weight loss. Survival was neither influenced by BMI, nor the cytokine levels in the present study. The significant correlation of ESR with TNF-α suggested that ESR could provide valuable clue for considerable weight loss in the follow-up of NSCLC patients.

Reactivation of pulmonary tuberculosis in malignancy.

Aims and Background Deterioration of immunity due to local or systemic effects of the tumor itself and/or administered chemotherapeutics or radiotherapy may play roles in the reactivation of tuberculosis, increasing the mortality in patients with various malignancies. In a country with a high prevalence of tuberculosis such as Turkey, most people have inactive tuberculous lesions and tuberculin test positivity. Therefore, a prospective study was carried out to investigate the frequency of tuberculosis reactivation in patients with a malignancy. Methods Seventy-three patients with a malignancy and undergoing diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year period (1993-1995). Bronchoscopic biopsies and cytologic materials were obtained. Bronchoalveolar lavage fluids, bronchial washings, and pre- and post-bronchoscopic sputum specimens were also evaluated for acid-fast bacilli. A diagnosis of tuberculosis was based on smear and/or culture positivity for acid-fast bacilli. Results The mean age of the patients was 56.2 ± 13.6 years, with a male/female ratio of 69/4. The biopsy proven malignancies were as follows: primary lung carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%). Thirty-one of all patients had findings compatible with tuberculosis on radiology. The sputa and bronchial washing specimens were smear negative in all patients. Acid-fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n = 5; non-Hodgkin lymphoma, n = 1). Four of these 6 patients had positive radiology for tuberculosis. These subjects were treated with a three- or four-drug anti-tuberculosis regimen. Two months later, smears remained acid-fast bacilli negative, or no bacilli were grown on culture. Conclusions The possibility of coexisting tuberculosis should be kept in mind in patients with a malignancy, especially those with lung carcinoma in countries with a high prevalence of tuberculosis. Pulmonary infections encountered in such patients should raise the suspicion of tuberculosis reactivation, and in addition to direct microscopic evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy should be cultivated for tuberculosis. Three-four-drug anti-tuberculosis regimens should be given, especially in countries with high drug-resistance rates for eradicating tuberculosis.

Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.

Tracheobronchial variations in Turkish population.

The tracheobronchial tree exhibits highly individualistic features and many variations. As the anatomic variations among Turkish population have not been studied previously, we aimed to evaluate the type and frequency of tracheobronchial variations (TBVs) in our bronchoscopy population. In a 3‐year period, 1,114 patients underwent flexible bronchoscopy (FB). Among these, 780 (70%) were male. The mean age of the patients was 51.3 ± 15.1 (range: 17–84) years. In 639 cases, no TBV were detected. A total of 999 TBV were observed in 475 patients. Of all, 71.3% (713) of the total TBV were detected in males. Forty‐nine and six‐tenths percent (49.6%) of the TBV were observed on the right bronchial system, 49.2% on the left, and 1.2% in the trachea. The five most frequently observed TBV were right lower lobe basal orifice with two subsegments, left lower lobe basal orifice with two subsegments, left upper lobe with three segments, right upper lobe with two segments, and right lower lobe with a subapical segment. In the same lobe bronchus, single variation and two different TBV were seen in 85% and 15% of patients, respectively. Number of TBV increased linearly with the number of lobes involved. The availability and popularity of FB in recent years has led to the increase in identification and reporting of TBV. TBV should be correctly identified and documented. This information is invaluable during follow‐up bronchoscopies as well as lung resection. Clin. Anat. 21:531–538, 2008.

Neuron-specific enolase and lung cancer.

Objective:Serum and bronchoalveolar lavage fluid (BALF) neuron-specific enolase (NSE) levels in lung cancer have been investigated widely; however, their diagnostic values have not yet been clarified. The authors investigated the diagnostic validity of NSE in BALF and serum in lung cancer. Materials and Methods:In this prospective case-control study, NSE levels in BALF (B-NSE) and serum (S-NSE) of 3 groups of subjects were analyzed: control subjects (group 1, n = 15), patients with chronic obstructive pulmonary disease (COPD; group 2, n = 15), and lung cancer (group 3, n = 35). Results:The differences in S-NSE and B-NSE levels between the groups were not significant (P > 0.05). S-NSE and B-NSE levels did not show any difference between smokers and nonsmokers, small cell lung cancer and nonsmall cell lung cancer patients, and stage I–II and stage III–IV patients in group 3 (P > 0.05). B-NSE or B-NSE/urea did not show any significance in comparison with S-NSE in the diagnosis and/or staging of malignancy (P > 0.05). S-NSE and B-NSE were well correlated with each other (r = 0.84, P = 0.000). The sensitivity of the S-NSE was 60% and the specificity was 40%. Conclusion:The authors conclude that, although elevation of B-NSE is a well-known parameter in small cell lung cancer, it can also be elevated considerably in nonsmall cell lung cancer and COPD. Because of the significant correlation between S-NSE and B-NSE, it may be sufficient to measure S-NSE activity because it is easier and less invasive. However, NSE has no role in the exact diagnosis of lung cancer; it can only be investigated in a scientific setting.

Evaluation of Cyfra 21-1: A Potential Tumor Marker for Non-Small Cell Lung Carcinomas

Abstract. Cyfra 21-1 is a tumor marker based on the determination of water-soluble cytokeratin 19 which is secreted by normal or malignantly transformed epithelial cells. It is suggested to be a valuable marker in patients with non-small cell lung carcinoma (NSCLC). A prospective clinical study was conducted to investigate the value of Cyfra 21-1 for diagnosis, determination of subtypes, staging, and evaluation of therapy response in patients with lung carcinoma (Ca). Sixty-nine patients (mean age: 60.9 ± 9.2 years, M/F:12.8) treated between 1994 and 1998 inclusive, and 13 healthy smokers (mean age:50.9 ± 4.8 years, M/F:1.6) constituted the study group and control group, respectively. Venous blood samples (10 ml) were obtained from all subjects. Posttreatment blood samples were also obtained from 14 NSCLC patients. Cyfra 21-1 levels (cutoff value 3.3 ng/ml) were determined by ELSA-Cyfra 21-1 kit (CIS bio international, France) through immunoradiometric assay (IRMA). Cyfra 21-1 levels did not differ between smoking and non-smoking subjects within each group (p > 0.05). Cyfra 21-1 was significantly elevated in lung Ca cases irrespective of the cell type (p < 0.05). It was significantly elevated in squamous cell and adenocarcinoma varieties with the most prominent elevation in squamous cell type (p < 0.05). In lung Ca, the specificity and sensitivity of Cyfra 21-1 was 92.3% and 52.2%, respectively. Sensitivity was 65.5% for NSCLC, 70.5% for squamous cell, and 45.5% for adenocarcinoma varieties, with highest sensitivity rates in Stage IIIA + IIIB (87.5%) and Stage IV (75%) of squamous cell lung Ca. Cyfra 21-1 level was significantly decreased after treatment in NSCLC patients (n 14) (p < 0.01). Cyfra 21-1 is a tumor marker that helps to establish the diagnosis and differentiation of cell type and evaluation of response to therapy in patients with NSCLC.

Clues for the differential diagnosis of hypersensitivity pneumonitis as an expectant variant of diffuse parenchymal lung disease.

Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, a type of diffuse parenchymal lung disease (DPLD), is an immunologically mediated pulmonary disease induced by inhalation of various antigens. As data on the frequency of hypersensitivity pneumonitis are lacking in Turkey, a retrospective analyses was performed in 43 patients with DPLD, followed up over seven years. The objective was to discover cases fulfilling the diagnostic criteria for hypersensitivity pneumonitis, to determine the frequency and/or the new characteristics of the disease, and to pick up clues for differentiating it from other DPLDs. The four subjects with hypersensitivity pneumonitis (9%) who lived in an urban area were studied in detail. The most common symptoms were dry cough and dyspnoea. According to the symptom duration, clinical features, radiological and pathological findings, three were diagnosed with chronic and one with subacute hypersensitivity pneumonitis. Patients with hypersensitivity pneumonitis and those with DPLD were compared by means of age, sex, smoking status, symptom duration, haematology, erythrocyte sedimentation rate, peripheral cell count, spirometric parameters, blood gases, and diffusion capacity. No statistically significant difference was detected in these parameters except for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). In conclusion, patients with a history of antigen exposure, with mild symptoms such as dry cough and dyspnoea, and who have diffuse interstitial lung involvement on radiology should be carefully evaluated for hypersensitivity pneumonitis. Moreover, among other DPLDs, stable FEV1 or FVC values may be the clues for establishing the diagnosis of hypersensitivity pneumonitis. However, further studies are needed in larger series of patients.

Gastric Signet-Ring Cell Adenocarcinoma Presenting With Left Arm Deep-Vein Thrombosis and Bilateral Chylothorax

A 28-year-old housewife, a life-long nonsmoker, presented with 3 weeks of pleuritic chest pain along with swollen right leg, left arm, and left breast. Six months previously she had left subclavian vein thrombosis. On admission, bilateral supraclavicular lymphedema on right leg and left arm and breast was observed and bilateral pleural fluid, chylous exudates, was detected. Abdomen computed tomography revealed abundant ascites and right ovarian enlargement. Whole body bone scintigraphy showed bone metastases on left humerus, right femur, and pelvis. Bronchial biopsy, obtained from edematous, hyperemic-irregular mucosa, revealed a carcinoma composed of signet-ring cells with intracytoplasmic mucin. Breast biopsy also showed signet-ring cells within the lymphatics. Pleural fluid cytology showed similar malignant cells. The patient was diagnosed as gastric signet-ring cell adenocarcinoma with endobronchial, mammary, ovarian, pleural, pericardial, peritoneal, and osteal metastases. The authors recommend that deep-vein thrombosis in unusual sites deserves further evaluation for an occult malignancy.

Cellular profile of bronchoalveolar lavage fluid in Turkish miners.

Pneumoconiosis is still a health problem in Turkey and has a relatively high incidence. Retired underground miners were investigated to document alveolitis, and to observe the difference in the cellular profiles of bronchoalveolar lavage (BAL) fluid with or without pneumoconiosis. Twenty nine retired male miners and 17 controls, eight non-smokers (four male, four female) and nine smokers (six male, three female), without any dust exposure were evaluated. According to the International Labor Office 1980 classification system, the miners were allocated to three subgroups: eight without pneumoconiosis, 11 with simple pneumoconiosis, and 10 with progressive massive fibrosis (PMF). Spirometric tests and arterial blood gases analysis were done and fibreoptic bronchoscopy and BAL were performed in all subjects. The study and the control subjects were comparable in respect to age, smoking habits, except the non-smoker controls, and the duration of dust exposure, except the controls. The amount of recovered BAL fluid was lower in all miners compared with the non-smoker controls (p<0.05). The amount of recovered BAL fluid and the total cell count correlated significantly (r = 0.48, p<0.01). The percentage of lymphocytes in the BAL fluid of miners without pneumoconiosis and with PMF (p<0.05) and that of simple pneumoconiosis (p<0.01) was significantly lower compared with the non-smoker controls. Alveolitis was not a representative feature of Turkish subjects with an occupational history of underground mining, and BAL fluid cellular profile did not seem to be different in miners with or without pneumoconiosis.