Aykut Cilli

The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04‐ and 1.60‐fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.

Doppler ultrasonography versus venography in the detection of deep vein thrombosis in patients with pulmonary embolism

In patients with acute pulmonary embolism (PE) the frequency of deep vein thrombosis (DVT) varies between 13–93%. The aim of this study was to compare Doppler ultrasonography (DUSG) and venography in the detection of DVT in patients with PE. Fifty-one patients who were clinically diagnosed as having PE from January 1st 2001 to January 31st 2005 were entered into the study and comorbid conditions and risk factors were noted. The diagnosis of PE was confirmed by ventilation-perfusion (V/Q) scintigraphy, spiral tomography and angiotomography while the diagnosis of DVT was made by DUSG and venography. DVT was confirmed by both DUSG and venography in 19 (37,3%) patients. In the remaining 32 patients DUSG was negative. Venography confirmed DVT in 6 of these patients while in 26 no DVT was found. The sensitivity and specifity of DUSG in the diagnosis of DVT were 76% and 100% respectively and the negative and positive predictive values were 81% and 100% respectively. The mean d-dimer concentration was 1187 in patients with DVT and 641 in patients without DVT (p > 0.05). Aquired risk factors were found in 4 of 6 patients with DVT, CRP was elevated in 5 (83%) and ALT-AST were elevated in 2 (33%). Although DUSG alone is considered sufficient for the diagnosis of DVT, venography still remains the gold standard in the diagnosis of DVT. Especially in patients with PE, where the diagnosis of DVT may increase the success of treatment, venography or other diagnostic tools may be used instead of a second DUSG if the first DUSG is negative.

The accuracy of autotitrating CPAP-determined residual apnea–hypopnea index

PurposeAutotitrating continuous positive airway pressure (auto-CPAP) devices not only titrate CPAP pressures but also measure residual respiratory events. The aim of the present study was to determine the accuracy of auto-CPAP-derived residual apnea–hypopnea index (AHI).MethodsWe studied 137 consecutive patients (72.3% men) with obstructive sleep apnea from January 2008 to December 2010 who underwent in-laboratory overnight polysomnography (PSG) using auto-CPAP. We excluded patients with comorbidities like congestive heart disease, chronic obstructive pulmonary disease, or hypoventilation syndromes and patients with central sleep apnea. Residual AHI obtained from the auto-CPAP device by smart card (CPAP-AHI) was compared simultaneously with AHI from an overnight PSG on auto-CPAP (PSG-AHI) using Bland–Altman analysis and Wilcoxon signed-rank test.ResultsThe mean AHI on the diagnostic study was 45.08 ± 1.8. During the titration, auto-CPAP markedly suppressed the respiratory events (PSG-AHI, 3.40 ± 0.20). On the other hand, CPAP-AHI was 3.35 ± 0.17. Bland–Altman analysis showed good agreement between auto-CPAP-AHI and PSG-AHI (AHI mean difference of 0.05, and the limits of agreement for the AHI were from +4.9 to −4.8). Two methods have also been compared with paired samples t test and no statistically significant difference was found (p > 0.05).ConclusionAuto-CPAP can identify residual respiratory events equivalent to the use of PSG in a selected population.

Omalizumab is effective in treating severe asthma in patients with severe cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25-hydroxyvitamin D and IL-1β levels

Background: There have been concerns about the cardiovascular safety of omalizumab. Objectives: In this study, the clinical status of the omalizumab receiving severe asthma patients and the cytokine expressions patterns were investigated. Materials and methods: In a pilot study described below we examined the levels of serum eosinophil cationic peptid (ECP), CD200, d-dimer, 25-hydroxyvitamin D (25(OH)D), CXCL8 and IL-1β in asthma patients treated with anti-IgE therapy, to explore their relationship with disease activity, and the impact of anti-IgE therapy impact on those levels. Exercise stress testing and blood samples were taken at all follow up visits from the time of first diagnosis and after 20 months of treatment during the disease remission. Results: Fractional exhaled nitric oxide concentrations and serum levels of sTRAIL, sCD200, D-dimer, ECP, total IgE, IL-1β and Hs-CRP were decreased while CXCL8, 25(OH)D were increased after starting the treatment of anti-IgE. Our first case of a patient, who had both protein C and S deficiency and hence a high risk for thromboembolism, documents for the first time the safety of omalizumab for asthmatic patients with concurrent risk factors contributing to arteriothrombotic events. Conclusion: Omalizumab might be used carefully in patients with cardiovascular diseases.

Assessment of subclinical left ventricular dysfunction in obstructive sleep apnea patients with speckle tracking echocardiography

In this study, our aim was to evaluate the LV (left ventricle) subclinical myocardial dysfunction using the two-dimensional speckle tracking echocardiography (2D-STE) method on obstructive sleep apnea (OSA) patients with preserved left ventricular ejection fraction (LVEF) and without any confounding disease that may result myocardial dysfunction. Twenty-one healthy individuals and 58 OSA patients were enrolled in the study. The patients were categorized into mild, moderate and severe OSA groups according to the apnea-hypopnea index (AHI). Conventional- and tissue Doppler echocardiography imagings were performed in all the individuals besides the 2D-STE. The longitudinal strain (S) and systolic strain rate (SRS) values decreased as the severity of disease increased from moderate towards severe OSA. The circumferential S and SRS values were observed to be lower in the severe OSA patients. Despite the increase in the radial S and SRS in moderate and mild OSA patients, these measurements decreased in those with severe OSA. Although the longitudinal, circumferential and radial early diastolic strain rates (SRE) decreased as the severity of disease increased form moderate to severe, the late diastolic strain rates (SRA) were observed to increase. In the early stages of OSA, longitudinal systolic LV dysfunction is detected in addition to the diastolic dysfunction. The circumferential mechanics of the LV deteriorate in the later stages of the OSA. Despite a compensatory increase in the radial LV function in the early stages of OSA, in later stages, the LV radial function also deteriorates. The assessment of the myocardial functions using the STE method in patients with OSA with preserved LVEF has the potential to detect the subclinical LV dysfunction and might provide useful information for risk stratification.

Omalizumab treatment in asthma-COPD overlap syndrome

Abstract Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a poorly understood disease with an increasing morbidity and mortality. Currently, the most effective treatment for ACOS is unknown and omalizumab for ACOS has not yet been reported. Methods: We report our experience with anti-IgE, omalizumab treatment on 3 patients with ACOS as a retrospective case study. Results: After 1 year of omalizumab treatment, patients experienced significantly lower rates of asthma exacerbation and hospitalization and better asthma control test results. Conclusion: Our study shows that omalizumab may be an effective and safe therapy for patients with ACOS. However larger randomized trials are needed.

Community-acquired pneumonia in patients with chronic obstructive pulmonary disease requiring admission to the intensive care unit: risk factors for mortality.

PURPOSE The aims of this study are to identify factors predicting mortality in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission and to examine whether noninvasive ventilation treatment reduces mortality. MATERIALS AND METHODS An analysis was performed on data from patients with CAP hospitalized in the ICUs of 19 different hospitals in Turkey between October 2008 and January 2011. Predictors of mortality were assessed by both univariate and multivariate statistical analyses. RESULTS Two hundred eleven patients with COPD and CAP were included. The overall ICU mortality was 23.9%. Noninvasive ventilation treatment (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.03-0.49; P = .003), hypertension (OR, 0.13; 95% CI, 0.02-0.93; P = .042), bilateral infiltration (OR, 13.92; 95% CI, 2.94-65.84; P = .001), systemic corticosteroid treatment (OR, 0.19; 95% CI, 0.35-0.96; P = .045), length of ICU stay (OR, 0.65; 95% CI, 0.47-0.89; P = .007), and duration of invasive mechanical ventilation (OR, 1.11; 95% CI, 1.01-1.22; P = .032) were independent factors related to mortality. CONCLUSION Noninvasive ventilation, hypertension, systemic corticosteroid treatment, and shorter ICU stay are associated with reduced mortality, whereas bilateral infiltration and longer duration of invasive mechanical ventilation are associated with increased risk of mortality in patients with COPD and CAP requiring ICU admission.

Takayasu’s Arteritis Presenting with Bilateral Parenchymal Consolidations and Severe Respiratory Failure

This is a report of an unusual case of Takayasu’s arteritis presenting with bilateral parenchymal infiltrations and severe respiratory failure caused by pulmonary hemorrhage. The patient was initially diagnosed and treated as protracted pneumonia. After the diagnosis of Takayasu’s arteritis, she was successfully treated with high-fractioned oxygen and corticosteroid therapy.

Mortality indicators in community-acquired pneumonia requiring intensive care in Turkey

BACKGROUND Severe community-acquired pneumonia (SCAP) is a fatal disease. This study was conducted to describe an outcome analysis of the intensive care units (ICUs) of Turkey. METHODS This study evaluated SCAP cases hospitalized in the ICUs of 19 different hospitals between October 2008 and January 2011. The cases of 413 patients admitted to the ICUs were retrospectively analyzed. RESULTS Overall 413 patients were included in the study and 129 (31.2%) died. It was found that bilateral pulmonary involvement (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.1-5.7) and CAP PIRO score (OR 2, 95% CI 1.3-2.9) were independent risk factors for a higher in-ICU mortality, while arterial hypertension (OR 0.3, 95% CI 0.1-0.9) and the application of non-invasive ventilation (OR 0.2, 95% CI 0.1-0.5) decreased mortality. No culture of any kind was obtained for 90 (22%) patients during the entire course of the hospitalization. Blood, bronchoalveolar lavage, and non-bronchoscopic lavage cultures yielded enteric Gram-negatives (n=12), followed by Staphylococcus aureus (n=10), pneumococci (n=6), and Pseudomonas aeruginosa (n=6). For 22% of the patients, none of the culture methods were applied. CONCLUSIONS SCAP requiring ICU admission is associated with considerable mortality for ICU patients. Increased awareness appears essential for the microbiological diagnosis of this disease.

Evaluation of long-term safety and efficacy of omalizumab in elderly patients with uncontrolled allergic asthma

BACKGROUND Severe asthma management in elderly patients may be difficult because of increased comorbid conditions, polypharmacy, physiologic changes that occur with aging, incorrect use of inhaler devices, and poor adherence. OBJECTIVE To evaluate the long-term safety and efficacy of the anti-IgE antibody omalizumab in elderly (aged ≥65 years) patients with uncontrolled allergic asthma. METHODS The efficiency and adverse effects of omalizumab treatment were evaluated based on data extracted from medical records. Patients were evaluated monthly for efficacy and adverse reactions. Treatment efficacy was evaluated by level of asthma symptom control, using the Global Initiative for Asthma guideline. RESULTS Nineteen consecutive elderly patients with asthma (female to male ratio, 14:5) formed our cohort. The mean (SD) age, disease duration, and total IgE level were 69.3 (5.8) years, 19.4 (8.6) years, and 299.1 (197.2) IU/mL, respectively. The mean (SD) duration of omalizumab treatment was 35.6 (17.8) months (range, 9-66 months). All the patients had at least 1 perennial inhalant allergen sensitivity and had uncontrolled allergic asthma. Elderly patients experienced no significantly important adverse reaction considered to be related to omalizumab treatment. Only 1 patient had a local adverse reaction and 1 had myalgia that was considered to be drug related. After omalizumab treatment, asthma symptoms were well controlled in 9 patients (47.4%) and partly controlled in 8 patients (42.1%). Two of the patients (10.5%) still had uncontrolled asthma. CONCLUSION Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with uncontrolled asthma.