Jerzy Soja

The Presence of Rhinovirus in Lower Airways of Patients with Bronchial Asthma

RATIONALE The common cold virus, human rhinovirus (HRV), is the most frequent cause of asthma exacerbations. However, a possible contribution of HRV to the pathogenesis of chronic, persistent asthma has not been defined. OBJECTIVES To determine if patients with stable asthma, who are free of clinical signs of a respiratory infection for at least 3 weeks, harbor HRV in their bronchi more frequently than nonasthmatic control subjects, and whether clinical features of asthma are associated with the presence of HRV. METHODS Immunohistochemistry and the indirect in situ reverse transcription-polymerase chain reaction method were used to detect the presence of HRV in bronchial mucosal biopsies in patients with asthma and nonasthmatic control subjects. MEASUREMENTS AND MAIN RESULTS HRV was found by immunohistochemistry in 9 of 14 bronchial biopsies from subjects with asthma (64.3%) and 2 of 6 nonasthmatic control subjects (33.3%) (P = 0.38). With the more sensitive indirect in situ reverse transcription-polymerase chain reaction method, HRV was found in the mucosal biopsies of 73% of patients with asthma and 22% of nonasthmatic control subjects (P < 0.001). Subjects positive for HRV had lower pulmonary function, higher numbers of blood eosinophils and leukocytes, and eosinophilic infiltration in bronchial mucosa. CONCLUSIONS HRV was detected in the lower airway tissue of patients with asthma significantly more often than in nonasthmatic subjects, and its presence was associated with clinical features of more severe disease.

Treatment of steroid-dependent bronchial asthma with cyclosporin

The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.

Endobronchial ultrasound-guided needle aspiration in the non-small cell lung cancer staging.

OBJECTIVE The aim of the study was to assess the diagnostic yield of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-NA) in the mediastinal staging in non-small cell lung cancer (NSCLC) patients. METHODS Consecutive NSCLC patients with enlarged or normal mediastinal nodes on CT scans underwent EBUS-NA. All patients with negative EBUS-NA subsequently underwent the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. RESULTS Two hundred and twenty-six patients underwent EBUS-NA between 1.02.07 and 30.04.08. There were 320 mediastinal lymph nodes biopsied (stations: 2R - 8, 4R - 83, 2L - 1, 4L - 61, 7 - 167). EBUS-NA revealed metastatic lymph node involvement in 129/226 patients (57.1%) and in 171/320 biopsies (53.4%). In 97 patients with negative EBUS-NA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in 16 patients (7.1%) - in 12 (5.3%) in stations accessible for EBUS-NA (stations: 4R - 3, 4L - 2, 7 - 8) and in 4 (1.8%) in stations not accessible for EBUS-NA (stations: 5 - 4, 6 - 1). All positive N2 nodes diagnosed by the TEMLA contained only small metastatic deposits. A diagnostic sensitivity, specificity, accuracy, PPV and NPV of EBUS-NA were 89.0%, 100%, 92.9%, 100% and 83.5%, respectively. No complications of EBUS-NA were observed. CONCLUSIONS (1) EBUS-NA is an effective and safe technique for mediastinal staging in NSCLC patients. (2) In patients with negative results of EBUS-NA, surgical exploration of the mediastinum should be performed.

Endobronchial ultrasound-guided needle aspiration in non-small-cell lung cancer restaging verified by the transcervical bilateral extended mediastinal lymphadenectomy — a prospective study

OBJECTIVES The aim of the study was to assess the diagnostic yield of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in restaging of the non-small-cell lung cancer (NSCLC) patients after neo-adjuvant therapy. METHODS In a consecutive group of NSCLC patients with pathologically confirmed N2 disease, who underwent neo-adjuvant chemotherapy, EBUS-TBNA was performed. All patients with negative EBUS-TBNA underwent subsequently the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. RESULTS A total of 61 patients underwent restaging EBUS-TBNA between 1 June 2007 and 31 December 2008. There were 85 mediastinal lymph nodes biopsied (stations: 2R - 2, 4R - 24, 2L - 1, 4L - 18 and 7 - 40). EBUS-TBNA revealed metastatic lymph node involvement in 18 of 61 patients (30%) and in 22 of 85 biopsies (26%). In 43 patients with negative or uncertain EBUS-TBNA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in nine patients (15%) - in seven (12%) in stations accessible for EBUS-TBNA (stations: 2R - 1, 4R - 5, 7 - 4) and in two (3%) in station not accessible for EBUS-TBNA (station: 5 - 2). The false-negative results of biopsies were found only in small nodes (5.8+/-2.8 mm x 7.5+/-2 mm). Moreover, all positive N2 nodes diagnosed by TEMLA contained only small metastatic deposits. There were three of 61 (5%) patients with false-positive results of biopsies in stations: 4R - 1, 4L - 1, and 7 - 2. A diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the restaging EBUS-TBNA was 67% (95% confidence interval (CI) - 65-90), 86% (95% CI - 82-95), 80%, 91% (95% CI - 80-100) and 78% (95% CI - 73-93), respectively. No complications of EBUS-TBNA were observed. CONCLUSIONS EBUS-TBNA is an effective and safe technique for mediastinal restaging in NSCLC patients, and after the data presented in our study, in patients with negative results of EBUS-TBNA, a surgical restaging of the mediastinum might not be mandatory.

The Use of Endobronchial Ultrasonography in Assessment of Bronchial Wall Remodeling in Patients With Asthma

BACKGROUND Endobronchial ultrasound (EBUS) is a new technique that enables the assessment of bronchial wall layers. The aim of the study was to verify the utility of EBUS for the assessment of bronchial wall remodeling in patients with asthma. METHODS In 35 patients with asthma and 23 control subjects, high-resolution CT (HRCT) scanning and EBUS were used to measure bronchial wall thickness in the 10th segment of the right lung. With a radial 20-MHz probe, EBUS identified the 5-laminar structure of the bronchial wall. Layer 1 (L(1)) and layer 2 (L(2)) were analyzed separately, and layers 3 through 5 (L(3-5)), which corresponded to cartilage, were analyzed jointly. Digitalized EBUS images were used for the quantitative assessment of bronchial wall thickness and the wall area (WA) of the layers. Finally, bronchial biopsy specimens were taken for measuring the thickness of the reticular basement membrane (RBM). The thickness and WA of the bronchial wall layers, which were assessed using EBUS, were correlated with FEV(1) and RBM. RESULTS There was no significant difference in the measurements of total bronchial wall thickness using EBUS and HRCT scanning. The thickness and WA of the bronchial wall and its layers were significantly greater in patients with asthma than in the control subjects. A negative correlation among the thicknesses of L(1), L(2), and L(3-5) and FEV(1), and a positive correlation with RBM were observed only in the patients with asthma. CONCLUSIONS EBUS allows precise measurement of the thickness and WA of bronchial wall layers. The correlation of these parameters with asthma severity suggests implementation of EBUS in the assessment of bronchial wall remodeling in patients with asthma.

Assessment of Airway Caliber in Quantitative Videobronchoscopy

Background: Quantitative assessment of airway caliber is generally confined to indirect methods. Fiberoptic bronchoscopy provides a direct view of the airways, but measurement of the internal size of bronchi in a standard examination is not possible. Using a special image analysis program, we developed a method allowing quantitative assessment of airway caliber by means of videobronchoscopic (VB) examination. Objectives: The purpose of the study was toshow that quantitative videobronchoscopy (VB coupled with a computer image analysis) allows direct and accurate measurement of the bronchi diameter. Methods: To test our hypothesis, we measured the same areas of a bronchial tree in CT and in VB in 40 patients with diagnostic indications for both the procedures. Results: We measured the diameters of 149 bronchi. The mean value of the difference between VB and CT measurements was equal to –0.071 mm and was not significantly different from 0 (p = 0.086). There was no obvious relation between the difference and the mean (r = 0.026, p = 0.745). The Bland Altman limits of agreement were L = –1.071 mm and U = 0.929 mm. We also assessed the bronchial diameter after endobronchial challenge and in patients with tracheobronchomalacia to show the application of this method for dynamic measurements. Conclusions: Quantitative videobronchoscopy allows the accurate and direct measurement of an airway caliber. It may be useful in clinical setting to quantify changes in a bronchial caliber (endobronchial masses, tracheobronchomalacia). Dynamic visualization of changes in airways may be useful in research, especially to explore the mechanics of airway narrowing.

Th2-Type Cytokine–Induced Mucus Metaplasia Decreases Susceptibility of Human Bronchial Epithelium to Rhinovirus Infection

Human rhinoviruses (RVs) are a major cause of exacerbations in asthma and other chronic airway diseases. A characteristic feature of asthmatic epithelium is goblet cell metaplasia and mucus hypersecretion. Bronchial epithelium is also an important source of lipid mediators, including pro- and antiinflammatory eicosanoids. By using air-liquid interface cultures of airway epithelium from patients with asthma and nonasthmatic control subjects, we compared RV16 replication-induced changes in mRNA expression of asthma candidate genes and eicosanoid production in the epithelium with or without IL-13-induced mucus metaplasia. Mucus metaplastic epithelium was characterized by a 20-fold less effective replication of RV16 and blunted changes in gene expression; this effect was seen to the same extent in patients with asthma and control subjects. We identified ciliary cells as the main target for RV16 by immunofluorescence imaging and demonstrated that the numbers of ciliary cells decreased in RV16-infected epithelium. RV16 infection of mucociliary epithelium resulted in overexpression of genes associated with bronchial remodeling (e.g., MUC5AC, FGF2, and HBEGF), induction of cyclooxygenase-2, and increased secretion of prostaglandins. These responses were similar in both studied groups. These data indicate that structural changes associated with mucus metaplasia renders airway epithelium less susceptible to RV infection. Thus, exacerbations of the lung disease caused by RV may result from severe impairment in mucociliary clearance or activation of immune defense rather than from preferential infection of mucus metaplastic epithelium. Repeated rhinoviral infections of compromised epithelium may contribute to the remodeling of the airways.

High-Resolution Computed Tomography Evaluation of Peripheral Airways in Asthma Patients: Comparison of Focal and Diffuse Air Trapping

Background: Air trapping evaluated in high-resolution computed tomography (HRCT) reflects changes in small bronchi. We simultaneously evaluated focal and diffuse air trapping in asthmatic patients. Objectives: (1) To evaluate air trapping and bronchial wall thickness in asthmatics. (2) To estimate the relationship between air trapping and bronchial wall thickness, pulmonary function tests (PFTs), age, gender and asthma severity. (3) To compare air trapping between subgroups of asthmatic patients with normal FEV1 % pred. and FEV1/FVC % and controls. (4) To compare air trapping and bronchial wall thickness between aspirin-induced asthmatics (AIA) and aspirin-tolerant asthmatics (ATA). Methods: Both groups (asthmatics and controls) included 30 patients. All patients underwent HRCT and PFTs. Results: Focal (p < 0.0001) and diffuse (p = 0.0004) air trappings and bronchial wall thickness (T: p < 0.0001; T/D: p < 0.0001; WA%: p < 0.0001) were significantly greater in asthmatics. Focal and diffuse air trappings were inversely correlated (p = 0.021). Diffuse air trapping correlated with bronchial wall thickness: T/D (p = 0.047), T (p = 0.037), and WA% (p = 0.048). There was a significant difference in the extent of focal air trapping between a subgroup of asthmatics with normal FEV1 % pred. and FEV1/FVC % and controls (p < 0.0001). There were no significant differences in focal (p = 0.095) and diffuse air trapping (p = 0.186) and bronchial wall thickness (T: p = 0.086; T/D: p = 0.428; WA%: p = 0.428) between AIA and ATA patients. Conclusions: Both focal and diffuse air trappings provide valuable diagnostic information and therefore deserve to be estimated. The lack of significant differences in air trapping and bronchial wall thickness between AIA and ATA patients needs further investigation.

Initial Polish experience of Flexible 19 gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

INTRODUCTION EBUS is a well established minimally invasive diagnostic tool for mediastinal and hilar lymphadenopathy. The novel ViziShot Flex 19G needle (Olympus Respiratory America, Redmond, WA, USA) was introduced in 2015 in order to improve loaded scope flexion and to obtain larger tissue samples for analysis. The aims of this study were to assess diagnostic yield of Flex 19G needles and to present endoscopists feedback about the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). MATERIAL AND METHODS The Flex 19G needles were used in patients with hilar and/or mediastinal adenopathy in two Polish pulmonology centers. Cytology smears and cell blocks (CB) were prepared. The prospective analysis was performed due to collected data. RESULTS Twenty two selected patients with confirmed adenopathy on chest-CT (mean age 58 ± 12) underwent EBUS-TBNA with use of Flex 19G needles. All procedures occurred to be diagnostic for smears (yield 100%). The malignancy was found in 15 cases (68.2%), and benign adenopathy in 7 (31.8%). In 12 of 14 cases of lung cancer (yield 85.7%) CB were diagnostic for immunohistochemical and molecular staining. After puncturing nodes, especially in hilar position not extensive bleeding was observed. Comparing to standard 21/22G EBUS-TBNA endoscopists underlined better flexion of loaded scope and sample adequacy and found non-significant differences in another biopsy details. CONCLUSIONS The first Polish experience with use of Flex 19G EBUS-TBNA needle occurs to be similar in performance with standard technique with use of 22/21G needles and presents high diagnostic yield for lung cancer diagnostics, especially when preparing CB. A safety profile of the biopsy is acceptable.

Renal interstitial mast cell counts differ across classes of proliferative lupus nephritis

Systemic lupus erythematosus frequently involves the kidneys leading to significant morbidity and mortality. It is classified according to glomerular involvement pattern but tubulointerstitial lesions are also important for progression and prognosis, as seen in other kidney glomerular diseases. One of the cell types which participate in this process are mast cells. The aim of the study was to analyze the counts of tryptase-positive and chymase-positive mast cells in lupus nephritis classes II, III and IV. Material consisted of 42 renal biopsies from patients with lupus nephritis; 11 class II, 9 class III and 22 class IV. Chymase- and tryptase-containing cells were stained by immunohistochemistry and counted microscopically. Mean count of chymase-positive mast cells was 9.8/10 high power fields (hpf) for the whole group, 4.66 for class II, 11.89 for class III, and 11.51 for class IV. The mean count of tryptase-positive cells was 18.6/10 hpf for the whole group, 7.65 for class II, 25.57 for class III, and 21.23 for class IV. The differences between lupus nephritis classes were significant both for chymase- and tryptase-positive cells. Tryptase- but not chymase-positive cell counts showed a correlation with the creatinine level (R = 0.35). These results suggest that mast cells are involved to a different degree in the pathogenesis of lupus nephritis depending on the class of the disease.