Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Elderly idiopathic pulmonary fibrosis patients remain on therapy despite higher incidence of adverse events and dose reductions.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) predominantly affects people over the age of 60 years and its incidence increases with age. Limited data is available on the use of antifibrotics in the elderly IPF population. We aimed to examine the tolerability and safety of antifibrotics (pirfenidone, nintedanib) in elderly patients with IPF in a real-world setting. METHODS: Medical records of 284 elderly (≥75 years) and 446 non-elderly IPF patients (<75 years) were retrospectively analyzed in this multi-center study. Patient characteristics, treatments, adverse events (AEs), tolerability, hospitalizations, exacerbations, and mortality were compared between the elderly and non-elderly group. RESULTS: In the elderly group, the mean age was 79 years and the mean antifibrotic treatment duration was 26.1 months. The most commonly reported AEs were weight loss, loss of appetite and nausea. Elderly IPF patients had a significantly higher incidence of AEs (62.9% vs. 55.1%, p = 0.039) and dose reductions (27.4% vs. 18.1%, p = 0.003) than the non-elderly did, but the rate of discontinuation of antifibrotics was not different between groups (13% vs. 10.8%, p = 0.352). In addition, the severity of the disease, frequency of hospitalizations, exacerbations, and mortality rates were higher in elderly patients. CONCLUSION: The present study showed that elderly IPF patients experienced significantly increased AEs and dose reductions due to antifibrotic use, while the discontinuation rates of the drugs were similar to those of drugs used by non-elderly patients.

Serum Krebs von den Lungen-6: promising biomarker to differentiate CPFE from IPF.

Background   Combined pulmonary fibrosis and emphysema (CPFE) has been recognised as a phenotype of pulmonary fibrosis. We aimed to compare serum surfactant protein-A (SP-A), surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels, functional parameters, in CPFE and  IPF (idiopathic pulmonary fibrosis) patients. Methods Patients diagnosed with 'CPFE' and 'IPF' were consecutively included in 6 months as two groups. The patients with connective tissue diseases are excluded. Results           In this study, 47 patients (41 males, 6 females) with CPFE (n = 21) and IPF (n = 26) with a mean age of 70.12 ± 8.75 were evaluated. CPFE patients were older, had more intense smoking history, had lower DLCO/VA, lower FVC, and worse six-minute walking distance than the IPF group (p=0.005, p=0.027, p=0.02, p<0.001, p=0.001, respectively). Serum KL-6 levels were higher in CPFE group compared to IPF group [264.70 U/ml (228.90-786) vs 233.60 (101.8-425.4), p<0.001]. Serum KL-6 levels of 245.4 U/ml and higher have 81% sensitivity and 73% specificity for the discrimination of CPFE from IPF. Conclusions   Our study has shown that serum KL-6 level is a promising biomarker to differentiate CPFE from IPF. In CPFE cases respiratory and functional parameters are worse than those of pure fibrosis cases.

Tocilizumab treatment in COVID-19: A prognostic study using propensity score matching.

BACKGROUND: The potential role of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) pneumonia provides the rationale for investigating IL-6 signaling inhibitors. OBJECTIVES: To evaluate and report treatment responses to tocilizumab (TCZ) in COVID-19 patients and compare mortality outcomes with those of standard care. MATERIAL AND METHODS: Patients hospitalized with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, diagnosed with reverse transcription polymerase chain reaction (RT-PCR) between March 2020 and April 2021, were enrolled in this single-center retrospective cohort study. Propensity score matching was performed in order to reduce confounding effects secondary to imbalances in receiving TCZ treatment. RESULTS: A total of 364 patients were included in this study. Two hundred thirty-six patients received standard care, while 128 patients were treated with TCZ in addition to standard care (26 (20.3%) patients received a dose of 400 mg intravenously once, while 102 (79.7%) patients received a total dose of 800 mg intravenously). In the propensity score-matched population, less noninvasive mechanical ventilation (p = 0.041) and mechanical ventilation support (p = 0.015), and fewer deaths (p = 0.008) were observed among the TCZ-treated patients. The multivariate adjusted Cox regression model showed a significantly higher survival rate among TCZ patients compared to controls (hazard ratio (HR): 0.157, 95% confidence interval (95% CI): 0.026-0.951; p = 0.044). The hazard ratio for mortality in the TCZ group was 0.098 (95% CI: 0.030-0.318; p = 0.0001 using log-rank test). CONCLUSIONS: This study determined that TCZ treatment in COVID-19 patients was associated with better survival, reduced need for mechanical ventilation and reduced hospital-associated mortality.

Characteristics and outcomes of COVID-19 patients with IPF: A multi-center retrospective study.

BACKGROUND: There are few data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) infection in patients with idiopathic pulmonary fibrosis (IPF). The objective of this study is to describe the characteristics and outcomes of IPF patients confirmed COVID-19 infection. METHODS: In this retrospective, multi-center, cohort study, patients from 4 hospital medical records with known IPF and a COVID-19 diagnosis were identified. Demographic and clinical outcome data were abstracted through a review of electronic medical records. RESULTS: Records for 46 patients with IPF and COVID-19 were abstracted. The mean age was 65±10 years. The most common symptom was dyspnea, followed by fever and cough. Ground-glass opacities (n = 35, 83.3%) and consolidations (n = 11, 26.1%) were the main imaging features of the disease in thorax computed tomography (CT). Twenty-four patients (52.1%) required hospitalization. Among the hospitalized patients, 16 (66.6%) were admitted to the intensive care unit (ICU), and 10 (41.6%) underwent invasive mechanical ventilation. Thirteen patients (28.2%) died of COVID-19 complications. Mortality rate was significantly associated with lower DLCO/VA, long term oxygen therapy and consolidation finding on CT of thorax (p<0.05). On multivariable analysis, neither factor was associated with hospitalization or mortality. CONCLUSIONS: IPF patients represent a vulnerable population for COVID-19, according to the high rate of hospitalization, ICU requirement, and mortality rate. Measures to minimize the risk of COVID-19 infection remain key to protect IPF patients.

Tolerability and efficacy of second-line antifibrotics in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The antifibrotic drugs nintedanib and pirfenidone reduce disease progression in idiopathic pulmonary fibrosis (IPF) and have also shown to improve survival. Switching first-line antifibrotic drug may required in IPF due to disease progression or intolerable adverse effects. The aim of this study was to assess the safety and efficacy of second-line antifibrotic treatment in patients with IPF. MATERIAL AND METHODS: This retrospective, multicenter study was conducted at three referral interstitial lung disease centers who received first-line antifibrotics more than one month and switched the treatment to a second-line antifibrotic agent during January 2016-June 2021. The drug's safety was evaluated based on the type of adverse effect. Disease progression was defined as an absolute decline in FVC of >10% within 12 months with or without radiological progression. RESULTS: Among 629 consecutive patients with IPF, 66 patients switched antifibrotics. The median duration of antifibrotics was 13 (1-41) months prior to the switch, and 14 (2-42) months after the switch. The mean age was 70.6 ± 8.9 years and, median FVC (%) was 72.1 ± 18.7 at the initiation of first-line antifibrotics. The most common reason for the switch was disease progression (56%) followed by severe adverse effects (SAEs) (44%). SAEs were significantly less observed after the switch compared before the switch (43.9% vs12.1%, respectively, p < 0.001). Eighteen patients had adverse effects due to second-line antifibrotics. Among these patients, 10 had mild adverse effects and 8 had severe adverse effects. While there was no change in the FVC (%) values in 30.3% patients 12 months after the first-line antifibrotic treatment (before the switch), there was no change in the FVC (%) values in 40% patients at the end of 12 months after the switch. Fourteen patients (42.4%) who received antifibrotic treatment before the switch had more than 10% decline in FVC (%) at the end of 12 months. Eight patients (32.0%) had 10% or more decline in FVC (%) 12 months after the switch. CONCLUSION: Patients with IPF who do not tolerate first-line antifibrotic treatment or those showing disease progression despite treatment, switching antifibrotics may be a feasible management strategy.

Evaluation of efficacy and safety of pirfenidone 200 mg tablets in patients with idiopathic pulmonary fibrosis in a real-life setting

Background/aim: Phase III trials have demonstrated a significant efficacy and an acceptable safety for pirfenidone in patients having mild to moderate idiopathic pulmonary fibrosis (IPF). Real-life data on the use of pirfenidone 200 mg tablets are limited. This study aimed to investigate the efficacy and safety of pirfenidone 200 mg tablets for the treatment of IPF in a real-life setting. Materials and methods: A retrospective, multicenter study conducted in four university hospitals in Turkey between January 2017 and January 2019. Clinical records of patients diagnosed with mild to moderate IPF and receiving pirfenidone (200 mg tablets, total 2400 mg/day) were reviewed retrospectively and consecutively. Pulmonary function measurements including forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) were analyzed at baseline and after 6-month of pirfenidone treatment. Descriptive statistics were expressed as mean, standard error or median (minimum-maximum), number and percentage, where appropriate. Results: The study included 82 patients, of whom 87.8% were males (mean age, 66 years). After 6-month of treatment, 7 patients discontinued the treatment. Of the remaining 75 patients, 71 (94.6%) remained stable, 4 (5.4%) had progressive disease as evident by a decline in the FVC% of at least 10% while on treatment, and 45 (61.3%) had improved cough. At least one adverse event (AE) associated with the treatment was observed in 28 (37.3%) patients. Conclusion: Pirfenidone 200 mg was effective and well tolerated and associated with relatively mild and manageable AEs in IPF patien

Effects of the COVID-19 pandemic on the follow-up and treatment of patients with idiopathic pulmonary fibrosis: a cross-sectional, multicentre phone call survey.

OBJECTIVE: To learn about the attitudes and behaviours of patients with idiopathic pulmonary fibrosis (IPF) in relation to the difficulties experienced during the COVID-19 pandemic. DESIGN: A cross-sectional, multicentre phone call survey. SETTING: Four university hospitals in Turkey. PARTICIPANTS: The study included patients with IPF receiving antifibrotics for at least 3 months and with doctor appointment and/or scheduled routine blood analysis between March and May 2020 (the first 3 months after the official announcement of the COVID-19 pandemic in Turkey). INTERVENTIONS: Phone calls (a 5 min interview) were performed in June 2020. A questionnaire and the Hospital Anxiety-Depression Scale were applied. MAIN OUTCOME MEASURES: Patients' preferences for disease monitoring, patients' attitudes and behaviours towards IPF, drug continuation, COVID-19 diagnosis and anxiety/depression status. RESULTS: The study included 115 patients with IPF (82 male; mean age, 68.43±7.44 years). Of the patients, 73.9% had doctor appointment and 52.2% had scheduled routine blood testing; 54.5% of patients with doctor appointment self-cancelled their appointments and 53.3% of patients with scheduled routine blood testing did not undergo testing. Of the patients, 32.2% were on nintedanib and 67.8% were on pirfenidone; self-initiated drug discontinuation rate was 22.6%. The percentage of patients communicating with their physicians was 35.7%. The route of communication was by phone (34.8%). The frequency of depression and anxiety was 27.0% and 38.3%, respectively. The rates of drug discontinuation (35.1% vs 16.7%, p<0.05) and depression (37.8% vs 21.8%, p=0.07) were higher in nintedanib users than in pirfenidone users. Only two (1.7%) patients had COVID-19 diagnosis. CONCLUSIONS: During the COVID-19 pandemic, a significant proportion (>50%) of patients self-cancelled their appointments and nearly a quarter of patients discontinued their medications. Providing a documentation of the problems experienced by patients with IPF about management of the necessary requirements during the COVID-19 pandemic, this study may be a model for patients with chronic diseases.

Is serum iron responsive protein-2 level associated with pulmonary functions and frequent exacerbator phenotype in COPD?

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) exacerbations contribute to the overall severity in individual patients because they are associated with airway inflammation, pulmonary function loss, decreased quality of life and increased mortality. Although, identifying frequent exacerbator patients is important due to severe outcomes associated with frequent exacerbator phenotype in COPD patients there is no single biomarker which can differentiate this phenotype. Iron responding protein-2 (IRP2) is the protein product of IREB2 gene, which is a COPD susceptibility gene that regulates cellular iron homeostasis and has a key role in hypoxic conditions. Previous research indicates that IREB2 expression in lung tissue is associated with spirometric measurements and emphysema in COPD. In this study, our aim was to investigate whether serum IRP2 levels were associated with frequent exacerbator phenotype, to evaluate whether IRP2 levels in serum are associated with pulmonary functions and selected systemic inflammation biomarkers. MATERIALS AND METHODS: Designed as a single tertiary care center based, crosssectional study, included high risk (GOLD C, D) COPD patients who admitted to outpatient clinic consecutively between December 2015 and July 2016. RESULT: The study included 80 COPD patients. Serum IRP2 levels were negatively correlated with FEV1 ml (r= -0.25, p= 0.02) and body weight (r= -0.35, p= 0.002) but not with markers of systemic inflammation. COPD patients with at least one exacerbation history in the last year tended to have higher IRP2 levels than patients without any exacerbation [12.3 (IQR 25-75: 10.4- 17.1) vs 10.5 (IQR 25-75: 8.8-18.5), p= 0.06]. CONCLUSIONS: Serum IRP2 level is significantly correlated with FEV1 mL but not with FEV1 % predicted and cannot be used to differentiate frequent exacer bator patients. Although IREB2 gene expressions in lung tissue and bronchoalveolar lavage results have significant associations with emphysema and FEV1/FVC, FEV1 %predicted in COPD patients, our results suggests serum IRP2 level is not as promising.

Diagnostic performance of EBUS-TBNA and its interrelation with PET-CT in patients with extra-thoracic malignancies.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic tool for lung cancer, sarcoidosis, and suspected metastatic extra-thoracic malignancy (ETM). Patients with primary ETM often have hypermetabolic mediastinal/hilar lymph node enlargement in the PET-scan done for initial staging or post treatment followup. We aimed to determine the diagnostic performance of EBUS-TBNA and the relationship between PET-SUV values and diagnosis of malignancy metastasis in patients with ETM. MATERIALS AND METHODS: Results of EBUS-TBNA in ETM patients with suspected MLN metastasis were retrospectively analysed (May 2016 to July 2019). Non-malign results were confirmed for surgery or clinical/radiological followup. Lymph nodes with a high FDG-uptake (SUV > 2.5, MLN) were reported as suspicious for metastasis. RESULT: Of the 588 EBUS procedures, 109 were included in the analysis. Patient' mean age was 62.5 ± 10.1 years; there were 35 men and 74 women. Primary malignancies were breast cancer in 33, gastrointestinal in 23, female genital tract in 17, head and neck in 14, genitourinary cancer in 13, malignant melanoma in 6, sarcoma in 2 and kaposi sarcoma in 1. According to EBUS-TBNA smear and cell block histopathologic evaluations, 16 patients' results (14.7%) were malignant compatible with metastasis of ETM. Among the 93 patients with non-malignant diagnosis, EBUS-TBNA revealed a granulomatous lympadenitis compatible with sarcoid reaction in 7 and tuberculosis in 2. A total of 9 patients underwent surgical procedures after EBUSTBNA, with a definitive histological diagnosis of granulomatous lymphadenitis in 2, malignancy in 5 and, reactive lymph node in 2. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were 76.19% (95% CI 52.83-91.78), 100% (95% CI 95.89-100.00), 100%, 94.62% (95% CI 89.12-97.12) and 95.4%, respectively. CONCLUSIONS: EBUS-TBNA sampling has high diagnostic performance. Histopathological confirmation requirement for MLN should be kept in mind in patients with ETM, even they have negative EBUS results.

COPD and Osteoporosis: Associated Factors in Patients Treated with Inhaled Corticosteroids.

Purpose: Osteoporosis is a systemic skeletal disease with a consequent increase in fractures rates. Osteoporosis may be primary which is related with normal aging, or secondary which occurs in the presence of an underlying disease or medication. Osteoporosis is one of the significant comorbidities in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate the presence of osteoporosis and the influencing factors in COPD patients. Patients and Methods: This is a two-group comparison study that was conducted among 30 COPD patients on inhaled corticosteroid (ICS) and 33 controls. It was conducted in the outpatient clinics at the Departments of Physical Medicine and Rehabilitation and Pulmonary Diseases in Bursa Uludag University Hospital, a tertiary reference center, in the northwest region of Turkey. For both groups, demographic variables, osteoporosis risk questioning, body mass index (BMI), bone mineral density (BMD), biochemical blood tests, vertebral fractures on lumbar and thoracic x-rays were recorded. COPD patients were also evaluated for lung functions via spirometry. Results: Thirty patients with COPD (Group 1) and 33 controls (Group 2) were included in the study. Comparing the demographic and biochemical data, no difference was found between the groups except smoking (pack/year) (p<0.001) and erythrocyte sedimentation rate (p<0.001), which were significantly high in COPD group. BMD in the COPD group was significantly lower in both hip and lumbar regions compared with the controls. There were significant correlations between L2 BMD values and pulmonary function tests. BMI was significantly low in osteoporotic COPD patients when compared with the non-osteoporotic COPD patients (p=0.002). Conclusion: In patients with COPD using inhaled corticosteroids, BMD was significantly low compared with the controls. Osteoporotic COPD patients had significantly lower BMI than non-osteoporotic. These findings suggest that pulmonary dysfunction and low BMI are associated with osteoporosis in COPD patients.

Three-dimensional analysis of craniofacial shape in obstructive sleep apnea syndrome using geometric morphometrics / Análisis tridimensional de la forma craneofacial en el síndrome de apnea obstructiva del sueño mediante morfometría geométrica

SUMMARY: Craniofacial morphology is a risk factor for obstructive sleep apnea syndrome. The general aim of this study was to investigate the craniofacial shape differences in adults with and without obstructive sleep apnea syndrome, using geometric morphometric methods. A descriptive study conducted in 106 adult Turkish subjects, consisting of 50 patients with OSAS diagnosed by polysomnography and 56 non-OSAS controls. Three dimensional craniofacial scanning processes were performed on patient subjects on the same day as the PSG. Twelve standard craniofacial landmarks were collected from each subject's 3D craniofacial scan. Geometric morphometric analysis was used to compare the craniofacial shape differences between the OSAS and non-OSAS control groups. No statistically significant difference in terms of general shape in face shapes was found between the OSAS group and control group. However, local significance differences were found. There were significant differences between the groups in some of the interlandmark distances: 11 % of the interlandmark distances were greater in OSAS patients, and 29 % were greater in controls. Greater measured distances in OSAS are concentrated in the nasal region. In the control group, the difference is not concentrated in a specific region. Given the relationship of craniofacial structural alterations and sleep disordered breathing, we hypothesized that inter-landmark distance measurements in the craniofacial anatomy of patients might be predictive of OSA.

RESUMEN: La morfología craneofacial es un factor de riesgo para el síndrome de apnea obstructiva del sueño. El objetivo general de este estudio fue investigar las diferencias de forma craneofacial en adultos con y sin síndrome de apnea obstructiva del sueño utilizando métodos morfométricos geométricos. Un estudio descriptivo realizado en 106 sujetos turcos adultos, de 50 pacientes con SAOS diagnosticados mediante polisomnografía y 56 controles no SAOS. El proceso de escaneo craneofacial tridimensional se realizó en pacientes sujetos el mismo día que el PSG. Se recogieron doce puntos de referencia craneofaciales estándar del escaneo craneofacial 3D de cada sujeto. Se usó el análisis morfométrico geométrico para comparar las diferencias de forma craneofacial entre los grupos de control SAOS y no SAOS. No se encontraron diferencias estadísticamente significativas en términos de forma general en las formas de la cara entre el grupo SAOS y el grupo control. Sin embargo, se encontraron diferencias de significación local. Hubo diferencias significativas entre los grupos en algunas de las distancias interlandmark: el 11 % de las distancias interlandmark fueron mayores en los pacientes con SAOS y el 29 % en los controles. Las mayores distancias medidas en SAOS se concentran en la región nasal. En el grupo de control, la diferencia no se concentra en una región específica. Dada la relación de las alteraciones estructurales craneofaciales y la alteración de la respiración durante el sueño, planteamos la hipótesis de que las mediciones de distancias inter-hito en la anatomía craneofacial de los pacientes podrían ser predictivas de la SAOS.

The Outcome of Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: A Single-Center Study

Objective: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality among neutropenic patients undergoing chemotherapy for acute myeloid leukemia (AML) and stem cell transplantation. The aim of this study was to evaluate the real-life impact of posaconazole prophylaxis. Materials and Methods: Eighty-four adult patients were included with AML under remission induction chemotherapy and posaconazole prophylaxis. The 34 patients in the control group did not receive primary antifungal prophylaxis. The period between June 2006 and January 2009, when antifungal prophylaxis was not administered (control group), was retrospectively compared to the period between December 2010 and May 2012 when primary oral posaconazole prophylaxis was administered in similar conditions (posaconazole group) according to the use of antifungal agents for treatment, breakthrough infections, galactomannan performance, and the necessity for performing bronchoalveolar lavage (BAL) procedures. Results: The two groups were compared according to the use of antifungal agents; progression to a different antifungal agent was found in 34/34 patients (100%) in the control group and in 9/84 patients (11%) in the posaconazole group (p<0.001). There were four breakthrough IFIs (4/84, 4.8%) in the posaconazole group and 34 IFIs in the control group (p<0.001). In addition, 15/34 patients (44%) in the control group required BAL compared to 11/84 patients (13%) in the posaconazole group (p<0.001). Posaconazole treatment was discontinued within 7-14 days in 7/84 patients (8.3%) due to poor oral compliance related to mucositis after chemotherapy. Conclusion: Posaconazole appears to be effective and well-tolerated protection against IFIs for AML patients.

Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization.

INTRODUCTION: Chemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. MATERIALS AND METHODS: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. RESULTS: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001). CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026), although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL) subgroups did not achieve statistical significance (P=0.09). Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92). Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0.0001) and was found to be an independent risk factor for hospitalized exacerbations in the multivariable analysis. CONCLUSION: CCL-18 is a promising biomarker in COPD, as it is associated with frequency of exacerbations, particularly with severe COPD exacerbations requiring hospitalization, as well as with functional parameters and symptom scores.

Fatal breakthrough infection with Fusarium andiyazi: new multi-resistant aetiological agent cross-reacting with Aspergillus galactomannan enzyme immunoassay.

Disseminated infections caused by members of the Fusarium fujikuroi species complex (FFSC) occur regularly in immunocompromised patients. Here, we present the first human case caused by FFSC-member Fusarium andiyazi. Fever, respiratory symptoms and abnormal computerised tomography findings developed in a 65-year-old man with acute myelogenous leukaemia who was under posaconazole prophylaxis during his remission-induction chemotherapy. During the course of infection, two consecutive blood galactomannan values were found to be positive, and two blood cultures yielded strains resembling Fusarium species, according to morphological appearance. The aetiological agent proved to be F. andiyazi based on multilocus sequence typing. The sequencing of the internal transcribed spacer region did not resolve the closely related members of the FFSC, but additional data on partial sequence of transcription elongation factor 1 alpha subunit did. A detailed morphological study confirmed the identification of F. andiyazi, which had previously only been reported as a plant pathogen affecting various food crops.

Comparative evaluation of galactomannan optical density indices and culture results in bronchoscopic specimens obtained from neutropenic and non-neutropenic patients.

Aspergillus infections are major causes of morbidity and mortality among immunocompromised patients. This study was designed to investigate the galactomannan assay optical density (OD) indices relative to the culture results in bronchoscopic samples obtained from neutropenic and non-neutropenic patients. Galactomannan OD indices from 1427 samples from 2005 to 2012, which were sent from 839 patients and were composed of bronchial lavage (BL = 727) and bronchoalveolar lavage fluids (BAL = 700), were retrospectively analysed. The recovery rates of Aspergillus species from these specimens were 9.4% from the combined patient group and 13.3% from the neutropenic group. Aspergillus fumigatus complex was the most frequently isolated species. The mean and median OD indices of the positive and negative culture samples are approximately 5 and 1, respectively, and 91% of all culture-positive samples have ≥1 OD index value. The receiver-operating characteristics curve analysis demonstrated that the feasibility of the Aspergillus galactomannan assay and Aspergillus galactomannan test has superior accuracy in BAL compared to BL fluids, and the test is not affected by the immune status of the patient. We suggest that the Aspergillus galactomannan test, which uses bronchoscopic material, leads to an earlier diagnosis and if the OD index is found ≥1, fungal growth can be expected.

Association between self reported snoring, STOP questionnaire and postoperative pulmonary complications in patients submitted to ortophaedic surgery.

BACKGROUND: Obstructive sleep apnea (OSA) may increase perioperative complications. The aim of this study was to determine the relationship among postoperative pulmonary complication, snoring and STOP questionnaire in patients with ortophaedic surgery. METHODS: 1,406 consecutive records of patients who had undergone elective ortophaedic surgery during the period January 2005-December 2008 were investigated retrospectively. Demographic information, sleep symptoms, STOP questionnaire, comorbidities and outcome data were collected. RESULTS: There were 289 (20.5%) snorers and 1,117 (79.5%) non-snorers in the study group. There was no significant difference between snorer and non-snorer patients (p > 0.05) in the prevalence of pneumonia and respiratory failure. But in snorer patients the rate of postoperative atelectasis was significantly higher than in non-snorer group (p < 0.0001). The STOP Questionnaire was given to 1,406 patients and 147 (10.4%) out of them were classified at high risk of OSA. There was no significant difference in the prevalence of pneumonia and respiratory failure between low and high risk group (p > 0.05). However, in high risk patients the occurrence of postoperative atelectasis was significantly higher than in low risk group (p < 0.0001). CONCLUSION: Postoperative atelectasis was significantly more prevalent in the high risk group according to STOP questionnaire.

[The Pneumocystis jirovecii colonization in bronchoalveolar lavage (BAL) and bronchial washing and the comparison of methods which are used in diagnosis]. / Bronkoalveoler lavaj (BAL) ve bronsiyal lavaj yapilan hastalardaki Pneumocystis jirovecii kolonizasyonu ve tanida kullanilan yöntemlerin karsilastirmasi

INTRODUCTION: Pneumocystis pneumonia (PCP) which is caused by Pneumocystis jirovecii is usually seen in the patients whose immune system is supressed. It is seriously seen an opportunist infection. In our study; totally 100 bronchoalveolar lavage (BAL) and bronchial washing samples collected by pulmonary disease department. Which belong to the patients in the clinics, and out patient clinic of the bronchoscopy material were evaluated. MATERIALS AND METHODS: The BAL and bronchial washing were evaluated by the help of methenamine silver stain (Gomori/Grocott), toluidine blue O stain, Wright-Giemsa stain, immun fluorescent antibody (IFA) stain, nested polymerase chain reaction (PCR). RESULTS: In the BAL and bronchial washing samples the agent couldn't be shown by the help of methenamine silver (Gomori/Grocott), toluidine blue O, Wright-Giemsa staining. In 13 patients with IFA test the cysts of P. jirovecii were determined. In 16 patients with nested PCR; the DNA of P. jirovecii were determined. In 8 patients by using PCR and IFA test P. jirovecii was determined. When the samples which had P. jirovecii were analyzed; 13 of them were BAL and 8 of them were bronchial washing. When the phenomenon groups were evaluated according to age, gender, smoking, hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), cerebrovascular accident (CVA), congestive cardiac failure (CCF), staying in the hospital in the last three months, using antibiotics and radiological findings; there wasn't a statistical meaningful relation between P. jirovecii positivity and these situations. When the phenomenon groups were evaluated according to PCR and IFA positivity; in IFA and PCR positive patients for immunosupressive there was a meaningful differances (p= 0.003). The positive 28.6 % of cases were immunosuppressed and the 3.8% of PCR or IFA negative cases were immunosupressed. When PCR method was compared with IFA which is called gold standard for sensitivity and specificity; sensitivity was found 61.5% and specificity was found 90.8%. IFA and PCR diagnosis test results were compatible (With McNemar test p= 0.581). CONCLUSION: Diagnostic sensitivity of staining methods for P. jirovecii in immunocompromised HIV negative patients are found to be low and it was shown that IFA and nested PCR methods have not parallel results.

The efficacy of nasal surgery in obstructive sleep apnea syndrome: a prospective clinical study.

The aim of this study was to investigate the effects of surgical intervention for nasal pathologies on obstructive sleep apnea syndrome (OSAS) and continuous positive airway pressure (CPAP) titrations in patients with OSAS. The study was designed as a prospective case control study. Between December 2007 and June 2010, 31 patients (26 men and 5 women) who were diagnosed with OSAS with polysomnography and confirmed to have obstructive nasal pathology were enrolled in the study. The average age of the patients was 53 ± 9.6 (range 33-68 years) and the body mass index ranged from 22 to 40.6 kg/m(2) with an average of 30.3 ± 4.1. The patients were evaluated with Epworth Sleepiness Scale, OSAS Complaints Questionnaire, visual analog scale, and CPAP titration before and 3 months after nasal surgery. As three patients did not attend the control polysomnography, data analysis was performed on 28 patients. Although there was a significant improvement in the nasal passage and subjective complaints, namely, snoring frequency, apnea and daytime sleepiness, the difference between preoperative and postoperative AHI values was not statistically significant. Postoperative CPAP titration results indicated a decrease both in pressures and in AHI in comparison to preoperative values. These reductions were not statistically significant, although the decrease in CPAP pressures was close to significance (p = 0.062). Nasal pathologies should be treated in all patients with OSAS, particularly those undergoing CPAP treatment. However, patients should be counseled that favorable results might not be achieved after nasal surgery.