Marta Maskey-Warzęchowska

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.

Bronchoalveolar lavage total cell count in interstitial lung diseases--does it matter?

Bronchoalveolar lavage (BAL) is a useful technique for differential diagnosis of various interstitial lung diseases (ILDs) and is usually realized by analysis of the differential cell count. This study was conducted to estimate the value of bronchoalveolar lavage fluid (BALF) total cell count (TCC) in the diagnosis of ILD. We analyzed 237 BAL samples from patients with ILD: sarcoidosis (SA), idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP), chronic eosinophilic pneumonia (CEP), and smoking-related ILD (sr-ILD). The control group consisted of 30 healthy volunteers. The statistical analysis revealed significant differences in the BALF TCC between healthy controls and patients with SA, IPF, HP, COP, sr-ILD, and eosinophilic disorders (mean values 6.9 vs. 14.5, 22.5, 22.8, 20.7, 64.5, and 27.3 × 106, respectively). Logistic regression revealed a significant relation between the TCC and ILD diagnosis. We conclude that the TCC, as well as the value of total number of inflammatory cells, should be reported in the description of BAL.

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.

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.

Simplified method of dynamic contrast-enhanced computed tomography in the evaluation of indeterminate pulmonary nodules.

Background: Dynamic contrast-enhanced computed tomography (CECT) is one of the methods used in the evaluation of lung nodules. Objectives: The aim of the study was to evaluate the accuracy of the simplified method (based on only 2 postcontrast measurements) of dynamic CECT in determining the nature of pulmonary nodules. Methods: Forty nodules (solid, 10–40 mm in diameter, spherical, with no visible calcification or fatty tissue) in 40 patients were analyzed. In 30 patients, the nature of the nodule was confirmed by pathological examination. In 10 cases, the nodules were assumed to be benign, as no growth within 2 years was radiologically documented. All patients underwent CECT according to a simplified protocol (based on pre-enhancement and 2 postcontrast measurements at 30 s and 4 min after contrast injection). Results: Twenty-three (57.5%) nodules were proved to be malignant and 17 (42.5%) benign. The 7 benign and none of the malignant nodules showed an enhancement value of ≤15 Hounsfield units. Thus, the sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of shortened dynamic CECT were 100, 41, 70, 100 and 75%, respectively. Conclusions: In CECT, contrast enhancement of a pulmonary nodule ≤15 Hounsfield units is a reliable predictor of its benignity. Reduction in the number of postcontrast measurements in the simplified method of dynamic CECT does not influence its sensitivity.

Pleural Effusion in Meigs’ Syndrome—Transudate or Exudate?: Systematic Review of the Literature

AbstractAlthough Meigs’ syndrome is regarded as a well-defined entity, contradictory data on pleural fluid characteristics have been presented, with some papers classifying it as a transudate, whereas others stating that it is an exudate.The aims of the study were: (1) to evaluate pleural fluid characteristics in patients with Meigs’ syndrome and (2) to analyze the prevalence of transudative and exudative pleural effusion in relation to the applied definition of the syndrome.We performed a search through medical databases (MEDLINE, EMBASE, SCOPUS, and GOOGLE SCHOLAR) to identify papers on Meigs’ syndrome published between 1940 and 2013. Two authors independently reviewed each paper searching for prespecified data: (1) signs and symptoms, (2) tumor characteristics, (3) clinical and laboratory data on ascites, (4) clinical, radiological, and laboratory data on pleural fluid, (5) clinical course after tumor removal. All case reports were reclassified according to a new unequivocal classification of Meigs’ syndrome-related entities.A total of 653 papers were initially identified, and 454 articles reporting 541 patients were included in the final analysis. After reclassification according to our case definitions, there were 196, 113, and 108 patients defined as classic Meigs’ syndrome, nonclassic Meigs’ syndrome, and pseudo-Meigs’ syndrome, respectively. Significantly more patients presented with right-sided than left-sided and bilateral pleural effusions (P < 0.001). Median volume of withdrawn pleural fluid was 2950 (1500–6000) mL. The classification of pleural effusion with the use of Lights criteria was possible in only 7 patients. In 6 of these patients pleural effusion met the criteria for an exudate. When the protein concentration > 3.0 g/dL was applied as a criterion of pleural exudate, 88.8% (80/90) of effusions were classified as exudates. Increasing the cut-off level to 3.5 g/dL resulted in only a modest decrease in the percentage of exudative effusions (81%, 73/90).Surprisingly few reports on Meigs’ syndrome present data reliably defining the character of pleural effusion. The available data indicate, however, that the majority of pleural effusions in patients with this entity are exudates. This finding may be a prerequisite for the verification of some earlier presented concepts.

Chronic cough – assessment of treatment efficacy based on two questionnaires

Introduction Efficacy of chronic cough treatment is ambiguous. The aim of the study was to analyze chronic cough alleviation after specific treatment and the relationship between cough etiology and treatment efficacy. Material and methods A stepwise diagnostic approach was used to diagnose cough etiology in non-smoking adults with chronic cough. In all patients specific treatment was applied. Two different questionnaires – a visual analog scale and a 5-degree scale – were used to assess cough severity before and after 4-6 months of treatment. Results A significant correlation between pre-treatment and post-treatment results of both questionnaires was found (Spearman coefficient 0.43, p = 0.0003 and 0.73, p < 0.0001, respectively). Baseline questionnaire analysis revealed no differences in cough severity between patients with different cough causes or multiple cough causes. Although specific treatment resulted in a significant decrease of cough severity in the entire group, only partial improvement was noted. According to the visual analogue scale, a decrease of cough severity by at least 50% was achieved only in 54.4% of patients (37/68). Similarly, satisfactory improvement was noted in only 54.4% (37/68) of patients when using the 5-point scale. There were three sub-groups of patients, in whom no relevant decrease of cough severity was observed despite treatment: patients with 1. three coexisting cough causes, 2. non-asthmatic eosinophilic bronchitis, and 3. chronic idiopathic cough. Conclusions Cough severity does not depend on its etiology. Efficacy of chronic cough treatment in non-smoking patients is only moderate.