Search

Introduction: Augmented Reality is a technique that enriches the real-life environment with 3D visuals and audio. It offers possibilities to expose medical students to a variety of clinical cases. It provides unique opportunities for active and collaborative learning in an authentic but safe environment. We developed an Augmented Reality application on the clinical presentation of shortness of breath (dyspnea), grounded on a theoretical instructional design model. Methods: A team of various stakeholders (including medical teachers and students) was formed to design the application and corresponding small group learning session, grounded on principles of instruction as described by Merrill. Evaluation was performed by an explorative questionnaire, consisting of open and closed questions (Likert scales), covering user experience, content and physical discomfort. Results: Multiple interactive cases of dyspnea were designed. The application plays back audio samples of abnormal lung sounds corresponding to a specific clinical case of dyspnea and displays a 3D model of the related pulmonary pathologies. It was implemented in the medical curriculum as an obligatory small group learning session scheduled preceding clinical clerkships. Prior knowledge was activated prior to the learning session. New knowledge was acquired with the application by solving an authentic problem based on a real patient case. In total 110 students participated in the study and 104 completed the questionnaire. 85% of the students indicated that the virtually auscultated lung sounds felt natural. 90% reported that the augmented reality experience helped them to better understand the clinical case. The majority of the students (74%) indicated that the experience improved their insight in the portrayed illness. 94.2% reported limited or no physical discomfort. Discussion: An Augmented Reality application on the presentation of dyspnea was successfully designed and implemented in the medical curriculum. Students confirm the value of the application in terms of content and usability. The extension of this Augmented Reality application for education of other healthcare professionals in currently under consideration.

A 42-year old male was referred with a 6-week history of new onset dyspnea. The patient had normal vital signs, no relevant medical history and the only abnormality was a left sided inspiratory wheeze. No abnormalities were seen on the chest X-ray. A bronchoscopy was performed which showed a well-circumscribed hypervasculated mass in the left main bronchus. A biopsy was taken, which was complicated after the procedure by dislocation of the mass and coughed up by the patient. Both samples were send for pathologic review. A contrast CT was performed which showed a localized remaining mass in the left main bronchus and no lymph node involvement. Pathological evaluation showed spindle-shaped cell proliferation with mitotic activity in the second larger tissue which could be consistent with an inflammatory myofibroblastic tumor (IMT), whereas the first biopsy sample only showed granulomatous inflammation. Following multidisciplinary review the diagnosis of IMT was made and a treatment plan was decided. Because of the localized position of the mass the patient was treated with laser coagulation via rigid bronchoscopy instead of surgery. Bronchoscopic review afterwards showed complete resolution of the mass and the dyspnea had resolved. This case highlights the difficulty of making the IMT-diagnosis and the option of treating it with laser coagulation via rigid bronchoscopy.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an allergic immunological response to Aspergillus fumigatus. In this study, we investigated whether certain Aspergillus antigens are more allergenic than others, as was postulated previously. We stimulated peripheral blood mononuclear cells from patients with ABPA with the classically described A. fumigatus allergens Aspf1, Aspf2, Aspf3, and Aspf4, as well as two other Aspergillus antigens, Crf1 and Catalase1. Activated CD4+ T cells displayed a T helper 2 phenotype with the production of IL-4 in response to stimulation with several of these different antigens. Immune responses were not limited to the classically described A. fumigatus allergens. In healthy individuals, we demonstrated a similar recognition profile to the different antigens, but in contrast the activated CD4+ T cells exerted a T helper 1 phenotype and mainly produced IFN-γ after stimulation with A. fumigatus antigens. In conclusion, irrespective of the A. fumigatus antigen, the T-cell immune response in patients with ABPA is skewed to a T helper 2 cytokine secretion profile.

Which inflammatory markers in the bronchial mucosa of asthma patients are associated with decline of lung function during 14 years of prospective follow-up?To address this question, 19 mild-to-moderate, atopic asthmatic patients underwent spirometry and bronchoscopy at baseline and after 14 years of follow-up (t=14). Baseline bronchial biopsies were analysed for reticular layer thickness, eosinophil cationic protein (EG2), mast cell tryptase (AA1), CD3, CD4 and CD8. Follow-up biopsies were stained for EG2, AA1, neutrophil elastase, CD3, CD4, CD8, CD20, granzyme B, CD68, DC-SIGN, Ki67 and mucins.Decline in forced expiratory volume in 1 s (FEV1) % predicted was highest in patients with high CD8 (p=0.01, both pre- and post-bronchodilator) or high CD4 counts at baseline (p=0.04 pre-bronchodilator, p=0.03 post-bronchodilator). Patients with high CD8, CD3 or granzyme B counts at t=14 also exhibited faster decline in FEV1 (p=0.00 CD8 pre-bronchodilator, p=0.04 CD8 post-bronchodilator, p=0.01 granzyme B pre-bronchodilator, and pLong-term lung function decline in asthma is associated with elevation of bronchial CD8 and CD4 at baseline, and CD8, CD3 and granzyme B at follow-up. This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes.

SummaryGiven the high degree of psychosocial problems in patients with lung cancer, quality medical care would benefit from exploring and addressing and providing potential solutions for these problems.Patients with recently diagnosed non-small-cell lung cancer filled out a questionnaire that assessed illness perceptions and made a drawing of how they perceived their diseased lungs look. They also participated in an interview about the impact of lung cancer in their lives.Scores on the Brief Illness Perception Questionnaire indicated that patients score low on ‘concern’, ‘emotional response’ and ‘timeline’, indicating they hope to be cured from lung cancer. Patients drew the tumor larger than it is on the chest radiograph. The drawings are moderately accurate representations of the patients' lungs. In the interviews patients often expressed their hopes of being cured and how thinking positively would help. Patients who made a more accurate drawing of their lungs had less optimistic views about their prognosis. These views are more in line with the prognosis their physician would give them. However, few patients made an accurate drawing.This study contributes to a better insight into what patients believe and feel about their disease. Suggestions for taking patient perceptions into account are provided.

Introduction Selected patients with stage III (N2/N3) non-small cell lung cancer (NSCLC) who are downstaged to N0 by chemoradiation therapy might benefit from subsequent surgical resection of the tumor. How mediastinal lymph nodes can be best reevaluated is subject of debate. Transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive technique to sample mediastinal nodes. We assessed sensitivity and false-negative rate of EUS-FNA for the mediastinal restaging of patients with stage III NSCLC. Methods Fifty-eight consecutive patients with stage III NSCLC and tissue-proven lymph node metastases N2/N3) who underwent EUS-FNA for restaging purposes after chemoradiation therapy were retrospectively analyzed. Surgical-pathological staging was used as the reference standard for nodal metastases. Results EUS-FNA found persistent nodal metastases (N2/N3) in 15 patients (26%). Of the 43 patients without persistent mediastinal metastases at EUS, 33 patients subsequently underwent surgical verification of the mediastinal nodes in whom persistent metastases (yN2/N3) were found in 19 patients (58%), and loco-regional downstaging (yN0) was achieved in the other 14 (42%). The prevalence of persistent nodal metastases in the 48 patients who could be analyzed was 71%. Sensitivity and the false-negative rate of EUS-FNA for mediastinal restaging were 44 and 58%, respectively. Discussion For mediastinal restaging of stage III NSCLC, EUS-FNA is a minimally invasive and safe method to confirm persistent nodal metastases, but this technique has a low negative predictive value and is therefore not useful for the exclusion of mediastinal metastases. Surgical restaging is indicated in the absence of mediastinal metastases at EUS-FNA.

Purpose A small-cell lung carcinoma (SCLC) is found in 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment. Patients and Methods A large nationwide cohort study of consecutive patients in the Netherlands, seen between 1990 and 2007, were screened for the presence of a tumor using chest x-ray, computed tomography of the thorax (CT-thorax), [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), bronchoscopy, and/or mediastinoscopy. Results SCLC was found in 54 patients, and in 46 patients, no tumor was found during a median follow-up of 8 years (range, 3 to 26 years). All patients with SCLC had a positive smoking history and 86% were still smoking at diagnosis. SCLC was found in 92% of these patients within 3 months and in 96% within a year. At first screening, CT-thorax detected an SCLC in 45 patients (83%), whereas chest x-ray found the tumor in only 23 patients (51%). An SCLC was found during secondary screening in another nine patients (median, 3 months; range, 1 to 41 months). In six patients, a lung tumor was found by CT-thorax or FDG-PET, and in three patients, extrapulmonary metastases were found, initially without identifiable tumor mass on CT-thorax. Conclusion In almost all patients (96%), the SCLC was found within 1 year of diagnosis. CT-thorax scans detected most of the tumors (93%) and was far more sensitive than chest x-ray (51%). FDG-PET may have additive value in selected cases. We propose a screening protocol based on CT-thorax and FDG-PET.

The progression-free survival (PFS) of cyclophosphamide/doxorubicin/etoposide (CDE) and carboplatin/paclitaxel (CP) was compared in chemonaive patients with extensive disease small-cell lung cancer (ED-SCLC). A total of 203 patients were randomised to three-weekly CDE (n=102) or CP (n=101) for five cycles. Tumour response rates in CDE and CP were 60% and 61%. PFS of CP was 5.2 months, PFS of CDE 4.9 months (p=0.60). The major difference in toxicity between CDE and CP was grade 4 leukocytopaenia in 64% and 9% of the patients (p This study failed to demonstrate any benefit in PFS with CP compared with CDE. CP was associated with significantly less haematological toxicity, leading to 37% less hospital admissions for febrile neutropaenia. (c) 2007 Elsevier Ltd. All rights reserved.

In November, 2013, a 16-year-old girl was referred with 2 days of fever, chest pain, dry cough, and progressive dyspnoea. She had a history of psychotic disorder, anorexia, pervasive developmental disorder not otherwise specifi ed, and self-harm. She had been admitted to a psychiatric facility 2 months previously and had been taking aripirazole for more than 3 months. She had no history of drug or toxin abuse but 2 weeks earlier had started smoking 10 cigarettes a day. 24 hours before admission her family doctor had started amoxicillin for presumed community acquired pneumonia. On examination she was unwell, with dyspnoea, tachypnoea, and oxygen saturation of 90% breathing ambient air. Auscultation showed extended expiration with bilateral crackles. Chest radiograph showed bilateral infi ltrates (appendix) and her infl ammatory markers were raised. Nebulised ipratropiumbromide and salbutamol were ineff ective, so we started oral amoxicillin–clavulanic acid and azithromycin for suspected atypical pneumonia. On day 3 she deteriorated with persistent fever and progressive tachypnoea and hypoxia. Chest sounds were absent on the right with diff use crackles on the left side. Repeat chest radiograph showed progressive bilateral infi ltrations and a right-sided pleural eff usion, but unexpectedly C-reactive protein had decreased from 92 mg/L to 32 mg/L. Because our patient had a pneumonia that was not resolving with standard antibiotic treatment we widened our diff erential diagnosis to include antimicrobial failure due to resistant or unusual micro-organisms (such as legionella), infectious complications (such as Staphylococcus aureus empyema), and noninfectious causes such as chemical pneumonitis, eosinophilic pneumonia, vasculitis, or diff use lung disease. We changed the antibiotics to fl ucloxacillin and ciprofl oxacin. Tests for respiratory viruses, HIV, chlamydia, legionella, tuberculosis, Pneumocystis jirovecii, nocardia, aspergillus, and toxoplasma were negative. Blood cultures were negative. Autoantibody and complement screening were normal. Thoracic CT showed ground glass opacities, peripheral patchy nodular and confl uent consolidations, and bilateral pleural eff usions (appendix). On the basis of her clinical condition, CT scan fi ndings, and recent start of smoking, we suspected an acute eosinophilic pneumonia. Bronchoscopy and bronchoalveolar lavage (BAL) showed no abnormalities apart from eosinophilia (27%) in the BAL (appendix). At the same time peripheral eosinophilia increased from 1% to 18%. Eosinophilic lung diseases are rare. Primary eosinophilic lung diseases consist of simple pulmonary eosinophilia, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, Churg Strauss syndrome, allergic bronchopulmonary aspergillosis, and idiopathic hypereosinophilic syndrome. Secondary eosinophilic lung diseases include all those caused by drugs, parasites, and fungi. The third group consists of systemic diseases associated with pulmonary eosinophilia such as sarcoidosis, malignant disease, and Langerhans cell histiocytosis. Our patient fulfi lled all criteria for acute eosinophilic pneumonia (table) and we had excluded other causes of pulmonary eosinophilia. A recent change in smoking habits is associated with acute eosinophilic pneumonia, as are other toxins. We started our patient on prednisolone, and after 48 h her symptoms of coughing and chest pain resolved and we could stop oxygen supplementation. 8 days later she refused treatment, including aripiprazole, and was transferred back to the psychiatric clinic. When she was discharged 13 days later she smoked 20 cigarettes in one day. That night her symptoms returned, accom panied by peripheral eosinophilia (12%), so we could confi dently attribute the acute eosinophilic pneumonia to cigarette re-exposure. A rebound event after stopping prednisolone cannot be excluded but has never been described, by contrast with relapse of acute eosinophilic pneumonia. She restarted prednisolone, but refused to keep taking the prednisolone 2 days later when she no longer needed oxygen therapy. At follow-up in December, 2014, she was healthy and not smoking. Acute eosinophilic pneumonia should be included in the diff erential diagnosis of pneumonia, especially in patients who have recently started smoking.

The objective of this phase II study was to document activity and toxicity of docetaxel and cisplatin as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) before definitive local treatment. Forty-six chemotherapy-nai¨ve patients (median age 60 years) were included. Treatment consisted of 3 cycles of docetaxel (85 mg/m2 on day 1), followed by cisplatin (40 mg/m2/day on days 1 and 2) every 21 days. Grade 3–4 leukopenia and neutropenia occurred in 45.7% and 65.2% of the patients, respectively. Among 8 cases of febrile neutropenia (17.4%), one (2.2%) resulted in early death. Common grade 3–4 non-haematological toxicities were nausea (17.4%) and vomiting (13%). Eighty-five percent of the patients received three courses; six stopped prematurely due to toxicity, one due to protocol violation. Response rate was the primary endpoint of this study. Considering eligible patients (n = 40), 18 responses (1 complete and 17 partial responses) were observed (response rate 45%; 95% Confidence interval (CI): 29.3%–61.5%). In stage IIIA-N2 NSCLC patients, docetaxel-cisplatin could be administered and demonstrated manageable toxicity with modest efficacy.

RATIONALE: Patients with asthma have an accelerated decline in lung function, which can lead to irreversible airway obstruction. It is generally assumed that this is related to specific aspects of airway inflammation and/or remodeling. OBJECTIVE: We investigated the prognostic significance of bronchial eosinophil and CD8+ cell counts and subepithelial reticular layer thickness for the subsequent decline in lung function in patients with asthma after 7.5 years of follow-up. METHODS: In a prospective study, pre- and post-bronchodilator lung function (FEV1) was measured at baseline, and after 2 years and 7.5 years in 32 patients with asthma. Annual decline in lung function after 7.5 years of follow-up was related to type and severity of airway inflammation and remodeling in bronchial biopsies, which were taken at baseline and at Year 2. RESULTS: Annual decline in post-bronchodilator FEV1 (mean [SD], 46.6 [53.4] ml/year) was significantly larger than the decline in prebronchodilator FEV1 (mean [SD], 27.5 [62.5] ml/year), indicating loss in reversibility. Although annual fall in post-bronchodilator FEV1 was not related to thickness of the reticular layer or to eosinophil counts in bronchial biopsies, there was a significant correlation with CD8+ T cells (r=-0.39, p=0.032). Analyzing the biopsies taken at Year 2, the significant association between annual fall in post-bronchodilator FEV1 and CD8 cells could independently be confirmed (r=-0.39, p=0.036). CONCLUSION: The outcome of asthma, as determined by the annual decline in FEV1, can be predicted by the bronchial CD8+ cell infiltrate. This suggests that the inflammatory phenotype in asthma has prognostic relevance, which may require phenotype-specific therapeutic strategies

Study objective: We hypothesized that transoesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has the potential to be a valuable and accurate new diagnostic technique for mediastinal restaging in non-small cell lung cancer (NSCLC) after induction chemotherapy. The current restaging modalities either have a low diagnostic accuracy (computed tomography (CT) scan of the thorax) or they are invasive, can be technically difficult and are therefore not commonly performed (remediastinoscopy). Methods and patients: Nineteen consecutive patients with NSCLC and proven ipsilateral or subcarinal lymph node metastases (N2 disease) who had been treated with induction chemotherapy underwent mediastinal restaging by EUS-FNA. Patients had either a partial response ( n =14) or stable disease ( n =5) based on sequential CT scans of the thorax. Interventions: EUS-FNA was performed in an ambulatory setting with biopsy of mediastinal lymph nodes (LN). No complications occurred. When EUS-FNA restaged the mediastinum as no regional lymph node metastasis (N0), surgical resection of the tumour with lymph node sampling or dissection was performed. Results: The positive predictive value, negative predictive value, sensitivity, specificity and diagnostic accuracy of EUS-FNA in restaging mediastinal LN were 100, 67, 75, 100 and 83%, respectively. Conclusions and significance: EUS-FNA qualifies as an accurate, safe and minimally invasive diagnostic technique for the restaging of mediastinal lymph nodes after induction therapy in NSCLC. In the future EUS-FNA might play an important role in the mediastinal restaging in NSCLC, particularly to identify the subgroup of down staged patients who benefit most from further surgical treatment.

Contains fulltext : 122998.pdf (Publisher’s version ) (Closed access) Small human lung specimens are frequently used for cell biological studies of the pathogenesis of emphysema. In general, lung function and other clinical parameters are used to establish the presence and severity of emphysema/chronic obstructive pulmonary disease without morphological analysis of the specimens under investigation. In this study we compared three morphological methods to analyze emphysema, and evaluated whether clinical data correlate with the morphological data of individual lung samples. A total of 306 lung specimens from resected lung(lobes) from 221 patients were inflated and characterized using three morphological parameters: the Destructive Index, the Mean Linear Intercept, and Section Assessment. Morphological data were related to each other, to lung function data, and to smoking behavior. Significant correlations (P < .001) were observed between Section Assessment and Destructive Index (r = 0.92), Mean Linear Intercept with Destructive Index (r = 0.69) and Mean Linear Intercept with Section Assessment (r = 0.65). Section Assessment, being much less time consuming than Mean Linear Intercept and Destructive Index, is the parameter of choice for initial analysis. Destructive Index is the most sensitive parameter. There was a significant (P < .001), but weak correlation for all three parameters with the diffusion capacity for CO (K(CO)) (Destructive Index: r = -0.28; Mean Linear Intercept: r = -0.34; Section Assessment: r = -0.32), and with FEV(1)/IVC (Destructive Index: r = -0.29; Mean Linear Intercept: r = -0.33; Section Assessment: r = -0.28), but not with other lung function parameters. A significant difference (P < .05) between (ex-) smokers and never-smokers was observed for Destructive Index and Section Assessment. It is concluded that the application of the three morphological parameters represents a useful method to characterize emphysematous lesions in a (semi-)quantitative manner in small human lung specimens, and that Section Assessment is a suitable and fast method for initial screening. The extent of emphysema of individual lung specimens should be established by means of morphometry, rather than lung function data.

Medical school museums are a permanent educational resource that provides access at the individual’s convenience. They may be considered a supplemental approach to providing graduate and postgraduate medical students with materials for the study of not only anatomy, but also of other basic and clinical sciences, such as embryology, pathology, and surgery. Also, they could be developed as a valuable tool for earning credits for mandatory continuing medical education (CME) requirements for physicians.

According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial involving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept diaries of symptoms, beta2-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0. 23 and 0.43 exacerbation/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p

Airway pathology is increasingly considered to be a major outcome in asthma research. The aim of this study was to examine the intra-observer, within-section and between-biopsy repeatability, together with the implications for statistical power of a computerized quantitative analysis of inflammatory cell numbers in the lamina propria in bronchial biopsy specimens from atopic asthmatic subjects. Thirty six atopic adults (aged 19-40 yrs) with mild to moderate asthma (baseline forced expiratory volume in one second (FEV1) > or =50% of predicted value, methacholine (PC20) range 0.02-18.2 mg x mL[-1]) at various levels of treatment (25 subjects on inhaled steroids) entered the study. Biopsies were taken from the (sub)segmental carinae of the right lower and middle lobe and from the main carina. Specimens were snap-frozen and immunohistochemical staining was performed on cryostat sections with monoclonal antibodies against: (secreted) eosinophil cationic protein (EG1, EG2), mast cell tryptase (AA1), CD45, CD22, CD4, CD8, CD25, and CD45RO. Using a computerized system, the number of positively stained cells in the lamina propria was counted. When considering all cell types together, satisfactory intraclass correlation coefficients (ICC) values were obtained for intra-observer, within-section and between-biopsy repeatability, being 0.90, 0.80 and 0.81, respectively. The analysis of repeatability for individual cell types revealed ICC values ranging 0.47-0.82 for intra-observer, 0.44-0.76 for within-section and 0.37-0.67 for between-biopsy repeatability. The results imply that a sample-size between eight and 25 subjects is needed to detect at least one doubling difference in cell number per 0.1 mm2 for a particular inflammatory cell type in a study, using a within-group design with alpha=0.05 and power of 0.80. A sample-size of 13-48 subjects per group is required to detect the same difference between the groups in a parallel design.

Chronic non-specific lung disease (CNSLD) encompasses asthma as well as chronic obstructive pulmonary disease (COPD). Recently in health care, there has been increasing awareness in the functional, psychological and social aspects of the health of patients; their quality of life (QOL). Quality-of-life research addressing CNSLD patients has been rather underdeveloped for a long period of time. Recently, however, the importance of QOL is being increasingly recognized, and several research groups have started to study QOL in CNSLD patients in more detail.This paper describes the construction of a disease-specific QOL instrument for patients with mild to moderately severe CNSLD. Items relating to several domains of QOL were listed, and 171 CNSLD patients in general practice were asked how much of a problem each item had been (assessed on a seven-point Likert scale). After applying an item-selection procedure, a uni-dimensional QOL questionnaire was constructed consisting of 55 items divided into seven domain subscales: breathing problems, physical problems, emotions, situations triggering or enhancing breathing problems, general activities, daily and domestic activities, and social activities, relationships and sexuality. Reliability estimates of the domain subscales of the constructed questionnaire varied from 0.68 to 0/sd89, and was 0/sd92 for the QOL for Respiratory Illness Questionnaire (QOL-RIQ) total scale. A first impression of the construct validity of the questionnaire was gained by investigation of the relationship between the QOL domain subscales and several indicators of illness severity, as well as the relative contribution of illness severity variables, background characteristics and symptoms to QOL, using regression analysis. Further research to validate the questionnaire to a greater extent (construct validity, test-retest reliability and responsiveness to change) is currently taking place.

The expression of the endogenous neuropeptide-degrading enzyme, neutral endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human airway epithelial cells can be upregulated by corticosteroids. We examined whether NEP expression in the airway epithelium or lamina propria in bronchial biopsies is enhanced in atopic asthmatics on regular inhaled steroids as compared with those without steroid treatment. Forty nonsmoking adults (age 19 to 48 yr) with mild to moderate asthma (forced expiratory volume in 1 s > or = 50% pred., histamine PC20 range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) regular inhaled steroids treatment entered the study. Biopsies were taken at (sub)segmental level from the right lower lobe, the middle lobe, and the main carina. Immunohistochemical staining was performed on cryostat sections using the VIL-A1 monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability of a semiquantitative scoring method was good as assessed by weighted kappa (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive sites were within the basal layer and, in contrast with studies applying other antibodies, also at apical sites and within the lamina propria. In both the epithelium and lamina propria, NEP expression was not significantly different between the three biopsy sites (Friedman's nonparametric two-way analysis of variance; P > 0.68), nor was expression in the lamina propria associated with inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression was significantly enhanced in the airway epithelium in patients using inhaled steroids as compared with nonsteroid users (mean rank: 23.4 and 15.5, respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was related to symptoms and the methacholine PC20 (Rs: -0.69 and 0.49, respectively; P

BACKGROUND: Current guidelines on the management of asthma advocate the use of anti-inflammatory treatment in all but mild disease. They define disease control in terms of clinical criteria such as lung function and symptoms. However, the relationship between the clinical control of the disease and inflammation of the airways is not clear. A cross sectional study was therefore undertaken to investigate the relationship between airways inflammation and measures of clinical control and bronchial hyperresponsiveness in asthmatic patients treated with inhaled steroids. METHODS: Twenty six atopic adults (19-45 years) with mild to moderate asthma (baseline forced expiratory volume in one second (FEV1) > or = 50% predicted, concentration of histamine causing a 20% fall in FEV1 (PC20) 0.02-7.6 mg/ml) on regular treatment with inhaled steroids entered the study. Diary card recordings during the two weeks before a methacholine challenge test and bronchoscopic examination were used to determine peak flow variability, symptom scores, and use of beta 2 agonists. Biopsy specimens were taken by fibreoptic bronchoscopy from the carina of the right lower and middle lobes, and from the main carina. Immunohistochemical staining was performed on cryostat sections with monoclonal antibodies against: eosinophil cationic protein (EG1, EG2), mast cell tryptase (AA1), CD45, CD22, CD3, CD4, CD8, CD25, and CD45RO. The number of positively stained cells in the lamina propria was counted twice by using an interactive display system. RESULTS: There were no differences in cell numbers between the three sites from which biopsy specimens were taken. The PC20 for methacholine was inversely related to the average number of total leucocytes, EG1+, and EG2+ cells, mast cells, CD8+, and CD45RO+ cells in the lamina propria. These relationships were similar for each of the biopsy sites. Symptom scores, beta 2 agonist usage, FEV1, and peak flow variability were not related to any of the cell counts. CONCLUSIONS: Infiltration of inflammatory cells in the lamina propria of the airways seems to persist in asthmatic outpatients despite regular treatment with inhaled steroids. The number of infiltrating leucocytes such as mast cells, (activated) eosinophils, CD8+, and CD45RO+ cells in bronchial biopsy specimens from these patients appears to be reflected by airway hyperresponsiveness to methacholine, but not by symptoms or lung function. These findings may have implications for the adjustment of anti-inflammatory treatment of patients with asthma.

Objective: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1 -> 3)-beta-D-glucan (beta-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients. Methods: HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum beta-D-glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum beta-D-glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. Results: In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum beta-D-glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients beta-D-glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. Conclusions: The level of serum beta-D-glucan-but not AdoMet - was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring. (C) 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

This study examined quality of life (QOL) and illness perceptions in Dutch and Japanese patients with non-small-cell lung cancer, thereby extending the body of knowledge on cultural differences and psychosocial aspects of this illness.24 Dutch and 22 Japanese patients with non-small-cell lung cancer filled out questionnaires on three occasions: immediately before chemotherapy, 1 week later, and 8 weeks after the initial chemotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assessed QOL, and the Brief Illness Perception Questionnaire (B-IPQ) illness perceptions.Scores on several QOL measures indicated (a) major impact of first chemotherapy sessions, and (b) some tendency to returning to baseline measures at 8 weeks. Differences between Japanese and Dutch samples were found on five EORTC QLQ-C30 dimensions: global health status, emotional functioning, social functioning, constipation, and financial difficulties, with the Dutch patients reporting more favorable scores. Regarding illness perceptions, Japanese patients had higher means on perceived treatment control and personal control, expressing a higher sense of belief in the success of medical treatment than Dutch patients.In both Japanese and Dutch patients, impact of chemotherapy on QOL was evident. Some differences in illness perceptions and QOL between the two samples were observed, with implications for integral medical management. Both samples reported illness perceptions that reflect the major consequences of non-small-cell lung cancer. Incorporating symptom reports, illness perceptions, and QOL into medical management may have positive consequences for patients with non-small-cell lung cancer.

From the early 19th century until the most recent two decades, open-space and satellite museums featuring anatomy and pathology collections (collectively referred to as "medical museums'') had leading roles in medical education. However, many factors have caused these roles to diminish dramatically in recent years. Chief among these are the great advances in information technology and web-based learning that are currently at play in every level of medical training. Some medical schools have abandoned their museums while others have gradually given away their museums' contents to devote former museum space to new classrooms, lecture halls, and laboratories. These trends have accelerated as medical school enrollment has increased and as increasing interest in biological and biomedical research activities have caused medical schools to convert museum space into research facilities. A few medical schools, however, have considered the contents of their museums as irreplaceable resources for modern medicine and medical education and the space these occupy as great environments for independent and self-directed learning. Consequently, some medical schools have updated their medical museums and equipped them with new technologies. The Anatomical Museum of Leiden University Medical Center in The Netherlands and the Medical Museum of Kawasaki Medical School in Kurashiki, Okayama, Japan, are two examples of such upgraded museums. Student surveys at Leiden University have indicated that all students (100%) found audio-guided museum tours to be useful for learning and majorities of them found guided tours to be clinically relevant (87%). However, 69% of students felt that museum visits should be optional rather than compulsory within the medical training curriculum. Anat Sci Educ 3:249-253. (C) 2010 American Association of Anatomists.

EUS-FNA has been reported to be a safe and accurate diagnostic method for investigating mediastinal lymph nodes (LNs) in patients with suspected lung cancer and sarcoidosis. The safety record of EUS-FNA in patients with mediastinal tuberculosis (TB) is unknown. We describe a patient with TB who developed mediastinal-esophageal fistulae after EUS-FNA of a tuberculous subcarinal LN.

Contains fulltext : 71473.pdf (Publisher’s version ) (Closed access) The aim of the present study was to evaluate the implementation of the 2003 Dutch guideline on the diagnosis and treatment of malignant pleural effusions, and the potential effect of the implementation on the clinical outcome of pleurodesis. All patients with malignant pleural effusion who had a pleural drain placed with the intention of performing pleurodesis were registered prospectively in four centres. Details of the procedure and fluid recurrence and survival data were noted. Patients with a proven malignancy (n = 100) were entered into the registration database. Diagnostic guideline recommendations were followed in 60-70% of the patients. Surprisingly, pleurodesis was performed in only 75% of the patients, mainly due to the presence of a trapped lung. All pleurodeses were performed using talc, according to the guideline. Follow-up revealed fluid recurrence in 27 (36%) patients after a mean follow-up of 17 days (range 2-285 days); 14 patients with successful pleurodesis died with a median survival of 61 days (range 13-174 days). Systemic treatment following pleurodesis and good apposition of the pleural surfaces during drainage were good prognostic factors. Despite reasonable-to-good adherence to the guideline, the number of successful pleurodeses was low. Better predictors of a good pleurodesis outcome are needed.

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema.

Background: The single-breath N-2 test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAIL, and induced sputum in patients with manifest COPD.Methods: Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV1, 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [Delta N-2], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretoij, leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid.Results: Delta N-2 increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with am, other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between Delta N-2 and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV1 percentage of predicted.Conclusions: The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.

Lambert-Eaton myasthenic syndrome is a rare, but reasonably well-understood, antibody-mediated autoimmune disease that is caused by serum auto-antibodies and results in muscle weakness and autonomic dysfunction. One half of the patients have an idiopathic form, the other half a tumour-associated form of the disease. Three randomised trials and a large number of smaller clinical studies have resulted in a number of drugs becoming available for the treatment of Lambert-Eaton myasthenic syndrome. Several drugs are available for the symptomatic treatment of the disease, including guanidine, aminopyridines or acetylcholinesterase inhibitors. Other therapies aim to deplete the serum autoantibodies or to suppress the immune system. For this purpose, immunomodulating strategies, such as intravenous immunoglobulins or plasmapheresis, or several immunosuppressive agents are available. Chemotherapy has successfully ameliorated the course of disease in Lambert-Eaton myasthenic syndrome patients with an underlying tumour.

ContextUp to 40% of thoracotomies performed for non–small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion (T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound–guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus.ObjectiveTo investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non–small cell lung cancer.Design, Setting, and PatientsProspective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non–small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed.InterventionThe EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients.Main Outcome MeasureDetection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone.ResultsThe combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval [CI], 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive.ConclusionThese preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.

Summary Background Induced sputum potentially allows monitoring of airway inflammation in patients with asthma in a non-invasive way. However, the relationship between the cellular content in sputum and airway tissue has not been fully clarified. Objective We compared the cellular compositions of hypertonic saline-induced sputum, bronchoalveolar lavage fluid (BAL) and bronchial biopsies in 18 clinically stable patients with mild to moderate atopic asthma (baseline FEV,: range 61-114%pred, PC20 methacholine: 0.04-4.7 mg/mL). They were treated with inhaled short-acting bronchodilators on demand, with (n = 8) or without (n = 10) regular inhaled steroids. Methods Each patient underwent sputum induction and fiberoptic bronchoscopy on separate days in random order. Differential cell counts of induced sputum, bronchoalveolar lavage and bronchial wash were determined on May-Grunwald-Giemsa stained cytospins. Flow cytometry was performed on sputum and BAL samples. Immunohistochemical techniques were used to stain inflammatory cells in 6 fxxn cryostat sections of bronchial biopsies. Results Sputum cell differentials were not different between the patients with and without inhaled steroids, and showed a median value of 19.4% squamous cells, with 1.0% eosinophils, 3.3% lymphocytes, 28.7% neutrophils, 49.4% macrophages and 6.9% cylindric epithelial cells (in percentage non-squamous cells). The percentage eosinophils in sputum was significantly correlated with their percentage in bronchial wash {R^ = 0.52, P = 0.03) and in BAL (/?s = 0.55, P = 0.02), whilst there was a trend towards such a correlation between the number of eosinophils/mL sputum and the number of EG2"'" eosinophils/mm^ lamina propria in bronchial biopsies (7?, = 0.44, P = 0.07). In addition, the percentage of CD4"*" lymphocytes correlated between sputum and BAL {R^ — Q.55, f = 0.03). Conclusion We conclude that the eosinophil counts in hypertonic saline-induced sputum from patients with asthma are related to those in bronchial wash and BAL and, to a lesser extent, with the counts in bronchial biopsies. This suggests that induced sputum can be used to monitor the presence and severity of airway inflammation in asthma.

Twenty-seven surgically removed lungs and lobes were studied to assess the relation between the abundance of bronchiolar epithelial cells containing antileukoprotease (ALP) (ALP-pos/mm) and the degree of small airways disease (SADscore) and emphysema (destructive index = DI, and number of normal alveolar attachments on membranous bronchioles = normal AA/min). Between subjects, ALPpos/mm correlated with SADscore in membranous bronchioles (rs = 0.75; p less than 0.001) and with normal AA/mm (rs = -0.38; p = 0.05). Evaluation within each subject revealed significant correlations of ALPpos/mm with SADscore in membranous as well as in respiratory bronchioles (p less than 0.001), and also with normal AA/mm (p = 0.005). In membranous and in respiratory bronchioles, ALPpos/mm correlated significantly with the ALP concentration in homogenized tissue, as measured by ELISA (rs = 0.55 and 0.57, respectively; p less than 0.01). It is concluded that disease in small airways and destruction of their alveolar attachments are associated with a rise of the number of ALP-containing epithelial cells. We hypothesize that this cellular increase is part of the general defense against inflammatory and destructive processes in distal human airways, leading to higher levels of proteinase inhibitor in order to minimize tissue damage.

The distribution of antileucoprotease in the lungs of 25 fetuses of 9-40 weeks' gestation was studied with monoclonal antibodies and an indirect immunoperoxidase technique. Antileucoprotease was detected from 16 weeks in submucosal glands and collecting ducts in the trachea and main and lobar bronchi: it was also found in the surface epithelium of the trachea at 20 weeks, in main and lobar bronchi at 20 weeks, and in smaller bronchi at 20-25 weeks. Non-ciliated cells containing antileucoprotease were observed in the bronchiolar epithelium at 36 and 40 weeks. The results of this study indicate that antileucoprotease is available from birth. It may therefore form part of the first line of defence of the lung.

RESUMO: A Asma, é uma doençã inflamatória crónica das vías aéreas caracterizada por episódios recorrentes de dispneia e sibilância que se associam a obstrução variavel das vias aéreas.Estes aspectos podem ser desencadeados em laboratório, pela exposição a estimulos broncoconstritores, demonstrando a existência de hiperreactividade brônquica (HRB).A inflamação das vias aéreas acompanhante caracteriza-se par um·infiltrado especifico de mastocitos, linfocitos e eosinófilos no epitelio brônquico e lamina propria e par um espessamento da camada reticular subendotelial, mesmo em doentes com asma ligeira. Deste modo, os aulores consideram que o estadio da doença deve ser determinado com base na gravidade dos sintornas, grau de limitação do fluxo aéreo, grau de hiperreactividade brônquica e inflamação das vias aéreas.De acordo com o Consenso Internacional (4), o principal objectivo do tratamento da Asma é reverter ou prevenir a inflamação das vias aéreas. A terapêutica, administrada de acordo com a gravidade da doença, baseiase apenas nos sintomas e na função pulmonar (determinação do débito expiratório máximo instantâneo-DEMI através da utilização do Peak-flow).Os autores referem que a inflamação das vias aéreas na asma, está associada com a hiperreactividade brônquica a estímulos broncoconstritores. Deste modo, postulam que a HRB pode serum elemento a considerar na terapêutica da asma, tendo investigado como a estratégia do tratamento baseada na HRB (estratégia HRB) em associação com as recommendações dos consensos internacionais (estratégia de referênda), conduzem a: 1) Controlo mais eficaz da asma; 2) Melhoria significativa da inflamação das vias aéreas.Para tal, os autores realizaram um ensaio randomizado, prospectivo, paralelo, envolvendo 75 adultos com asma ligeira a moderada, observados trimestralmente no período de 2 anos. Em cada visita foi avaliado o Volume Expiratório Máximo no 1° Segundo (VEMS) e realizada Prova de Provocação Inalada (PPI) com metacolina. Os doentes tinham cartões diários de registo de sintomas, de uso de β2-agonistas e determinações do DEMI.A terapêutica com corticosteróides (em 4 niveis) foi ajustada de acordo com as indicações 'em degraus' do Consenso Internacional (estratégia de refêrenda) as quais adicionaram 4 classes de gravidade da HRB (estrategia HRB): Nível I- HRB com metacolina - >4.0 mg/ml; Nível II-1.0 - 4.0 mg/ml; Nível III - 0.25 -1.0 mg/ml; Nível IV