Katarzyna Górska

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.

Airway inflammation in chronic obstructive pulmonary disease.

Purpose of review Understanding the chronic inflammatory process that affects the airways of patients with chronic obstructive pulmonary disease (COPD) is an important clue in the search for new therapeutic options. The main inflammatory cells and mediators involved in COPD pathogenesis have been identified, but there is still little knowledge about their mutual interactions that result in the final outcome, that is, structural airway changes and progressive airflow limitation. Recent findings Recent studies created novel theories on the inflammatory pathway in COPD and focused not only on the influence of cigarette smoke but also on other factors initiating airway inflammation. There is evidence that apart from neutrophils and macrophages, eosinophils may play an important role in the pathogenesis of COPD and patients with eosinophilic inflammation may present a distinct phenotype. This may have therapeutic implications. New cytokines (e.g. interleukin 32) involved in COPD pathogenesis have been identified. The increased number of inflammatory cell subpopulations need not necessarily be associated with their increased activity, suggesting their complex role in inducing/sustaining airway inflammation in COPD. The presence of inflammation in the upper airways in the course of COPD has also been found. Summary There are many questions concerning the pathogenesis of COPD yet to be answered. Results of recently published studies show a new approach to airway inflammation in COPD and indicate new interesting directions in COPD research.

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.

Airway dimensions in asthma and COPD in high resolution computed tomography: can we see the difference?

BACKGROUND: Airway remodeling in asthma and COPD results in bronchial wall thickening. The thickness of the bronchial wall can be measured in high-resolution computed tomography. The objectives of the study were to assess the bronchial lumen and wall dimensions in asthma and COPD patients, in relation to disease severity, and to compare the airway dimensions in patients with asthma and COPD. METHODS: Ten asthma subjects and 12 COPD subjects with stable, mild to moderate disease were investigated. All subjects underwent chest high-resolution computed tomography (window level − 450 Hounsfield units, window width 1,500 Hounsfield units). Cross-sections of bronchi (external diameter 1.0–5.0 mm) were identified on enlarged images. The following variables were measured: external and internal diameter, wall area, lumen area, total airway area, the percentage of airway wall area, wall thickness, and the ratio of wall thickness to external diameter. Separate sub-analyses were performed for airways with external diameter ≤ 2.0 mm and external diameter > 2.0 mm. RESULTS: We measured 261 and 348 cross-sections of small airways in subjects with asthma and COPD, respectively. There was a significant difference in wall thickness and wall area, which were both greater in asthmatics than in COPD patients. In bronchi with external diameter > 2.0 mm, all measured parameters were significantly higher in asthma than COPD. In individual asthmatics the airway wall thickness was similar in all the assessed bronchi, while in COPD it was related to the external airway diameter. CONCLUSIONS: Our results indicate that bronchial walls are thicker in asthmatics than in patients with COPD. It seems that airway wall thickness and the lumen diameter in patients with asthma are related to disease severity. There is no such a relationship in COPD patients. High-resolution computed tomography may be a useful tool in the assessment of airway structure in obstructive lung disease.

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.

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.

Eosinophilic and Neutrophilic Airway Inflammation in the Phenotyping of Mild-to-Moderate Asthma and Chronic Obstructive Pulmonary Disease

ABSTRACT Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with different inflammatory phenotypes. Various inflammatory mediators play a role in these diseases. The aim of this study was to analyze the neutrophilic and eosinophilic airway and systemic inflammation as the phenotypic characterization of patients with asthma and COPD. Twenty-four patients with asthma and 33 patients with COPD were enrolled in the study. All the patients were in mild-to-moderate stage of disease, and none of them were treated with inhaled corticosteroids. Concentrations of IL-6, neutrophil elastase (NE), matrix metalloproteinase 9 (MMP-9), eosinophil cationic protein (ECP), and IL-33 and IL-17 in serum and induced sputum (IS) were measured by enzyme-linked immunosorbent assay (ELISA). The cellular composition of blood and IS was evaluated. Hierarchical clustering of patients was performed for the combination of selected clinical features and mediators. Asthma and COPD can be differentiated based on eosinophilic/neutrophilic systemic or airway inflammation with unsatisfactory efficiency. Hierarchical clustering of patients based on blood eosinophil percentage and clinical data revealed two asthma clusters differing in the number of positive skin prick tests and one COPD cluster with two subclusters characterized by low and high blood eosinophil concentrations. Clustering of patients according to IS measurements and clinical data showed two main clusters: pure asthma characterized by high eosinophil/atopy status and mixed asthma and COPD cluster with low eosinophil/atopy status. The neutrophilic phenotype of COPD was associated with more severe airway obstruction and hyperinflation.

Continuous Positive Airway Pressure Treatment Increases Bronchial Reactivity in Obstructive Sleep Apnea Patients

Background: The effects of continuous positive airway pressure (CPAP) treatment on the function of the lower airways are poorly understood. One of the methods used to determine the influence of positive pressure breathing on lower airways is the bronchial hyperreactivity test. Some authors report that CPAP increases bronchial hyperreactivity, while others report decreases. Objectives: To assess the influence of CPAP treatment on bronchial reactivity and the effects of bronchial hyperreactivity on compliance to CPAP treatment. Methods: The study group consisted of 101 obstructive sleep apnea syndrome patients (88 men and 13 women) with a mean age of 51 ± 11 years, mean apnea-hypopnea index of 53 ± 20 and mean body mass index of 32.6 ± 5.4. Patients were randomly assigned to a treatment group that received 3 weeks of CPAP therapy (group 1) or to a nontreatment control group (group 2). Pulmonary function tests and the methacholine bronchial provocation test were performed at baseline and 3 weeks later. Results: There were no statistically significant differences between treated and control groups in anthropometry and polysomnography variables. At baseline, bronchial hyperreactivity was found in 6 patients from group 1 and 5 patients from group 2. A significant increase in bronchial reactivity was observed after CPAP treatment. Log PC20M decreased from 1.38 ± 0.30 at baseline to 1.26 ± 0.50 (p < 0.05). In group 2, changes were statistically insignificant. Patients with bronchial hyperreactivity during CPAP treatment were characterized by significantly lower FEV1, FVC and MEF50 values. Conclusions: CPAP produces statistically significant bronchial hyperreactivity. However, there were no clinical symptoms and it is not necessary to withdraw previous therapies.

Comparison of Small Bore Catheter Aspiration and Chest Tube Drainage in the Management of Spontaneous Pneumothorax

Beside standard chest tube drainage other less invasive techniques have been used in the management of patients with an acute episode of spontaneous pneumothorax. The aim of the study was to evaluate the short term effect of spontaneous pneumothorax treatment with small-bore pleural catheter and manual aspiration as compared to large-bore chest tube drainage. Patients with an episode of pneumothorax who required pleural intervention were enrolled in the study and randomly assigned to one of the treatment arms: (1) small-bore pleural catheter (8 Fr) with manual aspiration; (2) standard chest tube drainage (20-24 Fr). Success rate of the first line treatment, duration of catheter or chest tube drainage, and the need for surgical intervention were the outcome measures. The study group included 49 patients (mean age 46.9±21.3 years); with 22 and 27 allocated to small bore manual aspiration and chest tube drainage groups, respectively. There were no significant differences in the baseline characteristics of patients in both therapeutic arms. First line treatment success rates were 64% and 82% in the manual aspiration and chest tube drainage groups, respectively; the difference was insignificant. Median time of treatment with small bore catheter was significantly shorter than conventional chest tube drainage (2.0 vs. 6.0 days; p<0.05). Our results show that treatment of spontaneous pneumothorax with small-bore pleural catheter and manual aspiration might be similarly effective as is chest tube drainage in terms of immediate lung re-expansion.

Expression of Inflammatory Mediators in Induced Sputum: Comparative Study in Asthma and COPD

Asthma and COPD are the most common obstructive lung diseases characterized by inflammation in the lower airways which contribute to airflow limitation. Different inflammatory mediators are thought to play a key role in these diseases. This study was conducted in 13 patients with asthma, 12 patients with COPD, and 13 control subjects. The expression of mRNA of IL-6, IL-13, CXCL8, TSLP, IL-33, IL-25, IL-17, ECP, mast cell tryptase, CCL24, and CCL26 was assessed in induced sputum cells by real time PCR. We found that CXCL8 was strongly related to the neutrophil percentage but differed significantly in COPD and asthma patients. The expression of IL-17 was lower in patients with atopic asthma compared to non-atopic asthma. The percentage of macrophages correlated negatively with the expression of mast cell tryptase and ECP in COPD, and with CXCL8 in asthma. The expression of ECP correlated negatively with the severity of COPD symptoms measured by CAT. We conclude that asthma and COPD demonstrate a significant overlap in the airway cytokine profile. Thus, differentiation between the two diseases is difficult as based on a single cytokine, which suggests the coexistence of phenotypes sharing a common cytokine network in these obstructive lung diseases.