Piotr Korczynski

Incidence and aetiology of eosinophilic pleural effusion

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed. We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (≤40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample. Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.

Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis.

Purpose of review This review aims to define the role of adenosine deaminase (ADA) and interferon gamma (IFN-γ) in the differential diagnosis of pleural effusion with special attention to their source, mechanism of release and methods of measurement in pleural fluid. The diagnostic performance of ADA and IFN-γ is analyzed, and the advantages and limitations of their use in differentiating between tuberculous and nontuberculous pleural effusion are disucussed. Recent findings Several potential biomarkers of tuberculous pleurisy have been evaluated, but none have been found to be clearly superior to pleural fluid level of ADA or IFN-γ. The majority of recent studies confirm the high diagnostic utility of pleural fluid ADA and IFN-γ measurement; hence, these markers are included in different diagnostic algorithms for patients suspected of tuberculous pleurisy. Other relatively new tests show a high variability [nucleic acid amplification tests (NAATs)] or are technically demanding, costly and give equivocal results in patients with active tuberculosis [IFN-γ releasing assays (IGRAs)]. Summary Pleural fluid ADA and IFN-γ are both sensitive and specific biomarkers of tuberculous pleurisy. Their diagnostic accuracy across the different studies shows a smaller variability than that of other tests, for example NAATs. There is also no convincing evidence that IGRAs are superior to pleural fluid ADA or IFN-γ measurement. Hence, the role of ADA and IFN-γ in the differential diagnosis of tuberculous pleurisy is pivotal.

Lung ultrasound in the diagnosis and monitoring of community acquired pneumonia in children.

Lung ultrasound (LUS) is as an easily accessible, radiation-free imaging technique that might be used as a diagnostic tool in community-acquired pneumonia (CAP). The aim of the study was to evaluate the usefulness and accuracy of LUS in the diagnosis and monitoring of childhood CAP. One hundred six consecutive children aged between 1 and 213 (median 52.5) months referred to the hospital with suspicion of CAP were enrolled. All patients underwent LUS on the day of admission, followed by chest radiograph (CXR). Lung ultrasound was also performed in 25 children between 5th-7th and 31 children between 10th-14th day after admission. Radiographic signs of pneumonia were demonstrated in 76 children, while lung ultrasound revealed pulmonary abnormalities consistent with pneumonia in 71 children. LUS gave false negative results in 5 patients with parahilar pulmonary infiltrates demonstrated by CXR. Almost perfect overall agreement between LUS and CXR was found in terms of pneumonia diagnosis (Cohen kappa coefficient of 0.89). The diagnostic performance of LUS in demonstration of lung involvement was as follows: sensitivity of 93.4%, specificity of 100%, positive predictive value of 100%, negative predictive value of 85.7% and accuracy of 95.3%. Our study showed that LUS is a sensitive and highly specific diagnostic method in children with CAP. Therefore, LUS may be considered as the first imaging test in children with suspicion of CAP. A diagnostic algorithm of CAP which includes LUS should be validated in prospective studies. Lung ultrasound can also be used to follow-up resolution of pneumonic lesions.

DIAGNOSTIC UTILITY OF PLEURAL FLUID AND SERUM MARKERS IN DIFFERENTIATION BETWEEN MALIGNANT AND NON-MALIGNANT PLEURAL EFFUSIONS

Study objectiveTo evaluate the diagnostic value of four different tumor markers: cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron specific enolase (NSE) in patients with malignant and non-malignant pleural effusion.Material and methodsOne hundred and two patients with pleural effusion treated in the University Hospital in Warsaw between 2001 and 2003 were studied. They underwent an extensive, diagnostic work-up in order to determine the pleural effusion etiology. Patients with known pleural fluid etiology were labeled as the study group and submitted for further analysis. Pleural fluid and serum samples for CA-125, CEA, CYFRA 21-1 and NSE measurements were collected during the first thoracentesis, centrifuged, and frozen until further use. Pleural fluid and serum concentration of tumor markers were assessed by electrochemiluminescence methods using commercial kits.Results74 patients (32 M, 42 F; mean age 65 ± 14 years) composed the final study group. Exudative pleural effusion was found in 62 patients; of these 36 were malignant (48.6% of all effusions), 20 parapneumonic (or pleural empyema), and 6 tuberculous. In 12 patients, pleural transudate was diagnosed. The highest diagnostic sensitivity for malignant pleural effusion was found for NSE (94.4% and 80.6% in the pleural fluid and serum, respectively). However, the specificity of NSE measurement was relatively low (36.1% and 47.4% in pleural fluid and serum, respectively). The most specific markers of malignant pleural fluid etiology were pleural fluid CYFRA 21-1 and CEA levels (92.1% and 92.1%, respectively). CA-125 was found to be the most specific serum marker of pleural malignancies (78.9%). The AUC for combined pleural markers was 0.89, combined serum markers 0.82, combined ratio pleural/serum markers 0.88.ConclusionsThere are significant differences between the diagnostic value of various pleural fluid and serum markers. Overall, pleural fluid markers are superior to serum markers in determining the pleural fluid etiology. A combination of two or more tumor markers may help improve their diagnostic accuracy. Pleural fluid and serum measurements of different tumor markers play a limited role in the differentiation between malignant and non-malignant pleural effusions.

Obstructive sleep apnea in shift workers.

OBJECTIVE In modern society, the number of people working night shifts is increasing. The aim of the study was to investigate effects of shift work on obstructive sleep apnea syndrome (OSAS) and oxygen desaturation index (ODI) during daytime and nighttime sleep in patients with OSAS. METHODS Twenty-nine male and two female shift workers (SW) with OSAS were investigated. Their mean age was 47±10years, BMI 32±4kg/m(2). The control group consisted of 10 male patients with OSAS, matched for age, BMI, and hours of night sleep, not working on shifts. Nocturnal and diurnal after night shift or sleep deprivation polysomnographies (PSG) were performed in all subjects. RESULTS Comparison of diurnal and nocturnal PSG recordings in the SW group demonstrated a significantly higher AHI in diurnal PSG after the night shift vs. nocturnal PSG (50±27 vs. 32±22, P<0.05). During daytime sleep SW OSAS patients demonstrated higher AHI than sleep-deprived controls (49.7±26.6 vs. 30.1±21.9, P<0.05) and higher ODI (44.1±25.1 vs. 21.6±18.5, P<0.05). CONCLUSIONS Significantly higher severity of OSAS during daytime sleep after night shift may intensify unfavorable health effects of OSAS. Patients with OSAS if not effectively treated should avoid nighttime work.

Comparative study of periostin expression in different respiratory samples in patients with asthma and chronic obstructive pulmonary disease.

INTRODUCTION Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on periostin in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES The aim of the study was to evaluate periostin expression and to compare its concentrations in various materials in patients with mild-to-moderate asthma and COPD, as well as to evaluate the potential association between periostin and clinical features of both diseases. PATIENTS AND METHODS Using an enzyme-linked immunosorbent assay, we measured periostin concentrations in serum, induced sputum (IS), exhaled breath condensate (EBC), and bronchoalveolar lavage fluid (BALF) as well as periostin expression in bronchial biopsy samples in 24 patients with asthma, 36 patients with COPD, and 12 controls. Correlations between periostin levels in different materials were also analyzed and periostin concentrations were compared between patients with asthma and those with COPD. RESULTS Periostin levels were detectable in serum, IS, EBC, and BALF from patients with asthma, COPD, and controls. EBC periostin levels correlated with tissue periostin expression and were significantly higher in asthma than in COPD (P = 0.04). Periostin expression in bronchial mucosa was higher in asthma than in COPD (P <0.001), as well as in asthma and COPD patients compared with controls (P <0.001). No significant correlations between tissue periostin expression and BALF, IS, or serum periostin levels were found. There were no differences in serum, IS, BALF, or EBC periostin concentrations between patients with different phenotypes of both diseases. CONCLUSIONS Periostin may be detected not only in serum, IS, and airway tissue samples, but also in EBC and BALF. EBC periostin levels and tissue periostin expression are higher in patients with asthma than in those with COPD. EBC periostin levels may serve as a potential surrogate marker for tissue periostin expression.

MR Imaging of Pulmonary Nodules: Detection Rate and Accuracy of Size Estimation in Comparison to Computed Tomography.

Objective The aims of this study were to assess the sensitivity of various magnetic resonance imaging (MRI) sequences for the diagnosis of pulmonary nodules and to estimate the accuracy of MRI for the measurement of lesion size, as compared to computed tomography (CT). Methods Fifty patients with 113 pulmonary nodules diagnosed by CT underwent lung MRI and CT. MRI studies were performed on 1.5T scanner using the following sequences: T2-TSE, T2-SPIR, T2-STIR, T2-HASTE, T1-VIBE, and T1-out-of-phase. CT and MRI data were analyzed independently by two radiologists. Results The overall sensitivity of MRI for the detection of pulmonary nodules was 80.5% and according to nodule size: 57.1% for nodules ≤4mm, 75% for nodules >4-6mm, 87.5% for nodules >6-8mm and 100% for nodules >8mm. MRI sequences yielded following sensitivities: 69% (T1-VIBE), 54.9% (T2-SPIR), 48.7% (T2-TSE), 48.7% (T1-out-of-phase), 45.1% (T2-STIR), 25.7% (T2-HASTE), respectively. There was very strong agreement between the maximum diameter of pulmonary nodules measured by CT and MRI (mean difference -0.02 mm; 95% CI –1.6–1.57 mm; Bland-Altman analysis). Conclusions MRI yielded high sensitivity for the detection of pulmonary nodules and enabled accurate assessment of their diameter. Therefore it may be considered an alternative to CT for follow-up of some lung lesions. However, due to significant number of false positive diagnoses, it is not ready to replace CT as a tool for lung nodule detection.

Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease.

Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce.AimTo assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients.Material and methodsThe study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years). In all subjects lung function tests and HRCT scanning of the chest were performed. External (D) and internal (L) diameters of the airways were assessed at five selected lung levels. The lumen area (AL), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). Total and differential cell counts were assessed in the BAL fluid.ResultsMean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS). No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS). Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P < 0.05) and lumen area (r = -0.7, P < 0.05) were found in asthmatics. There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients.ConclusionsIn mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid.

Diagnostic Accuracy of Contrast-Enhanced Computed Tomography and Positron Emission Tomography With 18-FDG in Identifying Malignant Solitary Pulmonary Nodules

AbstractContrast-enhanced computed tomography (CECT) and positron emission tomography with 18-FDG (FDG-PET/CT) are used to identify malignant solitary pulmonary nodules. The aim of the study was to evaluate the accuracy of CECT and FDG-PET/CT in diagnosing the etiology of solitary pulmonary nodule (SPN).Eighty patients with newly diagnosed SPN >8 mm were enrolled. The patients were scheduled for either or both, CECT and FDG-PET/CT. The nature of SPN (malignant or benign) was determined either by its pathological examination or radiological criteria.In 71 patients, the etiology of SPN was established and these patients were included in the final analysis. The median SPN diameter in these patients was 13 mm (range 8–30 mm). Twenty-two nodules (31%) were malignant, whereas 49 nodules were benign.FDG-PET/CT was performed in 40 patients, and CECT in 39 subjects. Diagnostic accuracy of CECT was 0.58 (95% confidence interval [CI] 0.41–0.74). The optimal cutoff level discriminating between malignant and benign SPN was an enhancement value of 19 Hounsfield units, for which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CECT were 100%, 37%, 32%, and 100%, respectively. Diagnostic accuracy of FDG-PET/CT reached 0.9 (95% CI 0.76–0.9). The optimal cutoff level for FDG-PET/CT was maximal standardized uptake value (SUV max) 2.1. At this point, the sensitivity, specificity, PPV, and NPV were 77%, 92%, 83%, and 89%, respectively.The diagnostic accuracy of FDG-PET/CT is higher than that of CECT. The advantage of CECT is its high sensitivity and negative predictive value.

Diagnostic Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy

Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7%) patients with tuberculous pleural effusion, 88 (43.3%) patients with malignant pleural effusion, 35 (17.2%) with parapneumonic effusion/pleural empyema, 30 (14.8%) with pleural transudates, and 6 (3%) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97%, 98%, 95.5%, 99.4%, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC≥0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.