Large-Scale Plasma Proteome Epitome Profiling is an Efficient Tool for the Discovery of Cancer Biomarkers.

Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of system approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possesses dynamically changing availability of interacting surface structures that frequently serve as reachable epitopes and often carry different functions. Thus, it is highly likely that the presence of some of the accessible epitopes correlates with function under physiological and pathological conditions. To enable the exploration of the impact of protein variation on the immunogenic epitome first, here, we present a robust and analytically validated PEP technology for characterizing immunogenic epitopes of the plasma. To this end, we prepared mAb libraries directed against the normalized human plasma proteome as a complex natural immunogen. Antibody producing hybridomas were selected and cloned. Monoclonal antibodies react with single epitopes, thus profiling with the libraries is expected to profile many epitopes which we define by the mimotopes, as we present here. Screening blood plasma samples from control subjects (n = 558) and cancer patients (n = 598) for merely 69 native epitopes displayed by 20 abundant plasma proteins resulted in distinct cancer-specific epitope panels that showed high accuracy (AUC 0.826-0.966) and specificity for lung, breast, and colon cancer. Deeper profiling (≈290 epitopes of approximately 100 proteins) showed unexpected granularity of the epitope-level expression data and detected neutral and lung cancer-associated epitopes of individual proteins. Biomarker epitope panels selected from a pool of 21 epitopes of 12 proteins were validated in independent clinical cohorts. The results demonstrate the value of PEP as a rich and thus far unexplored source of protein biomarkers with diagnostic potential.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Background: Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. Methods: In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. Results: The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Conclusion: Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. Trial registration: NCT05812196.

Evaluation of cardiopulmonary exercise test in the prediction of disease progression in systemic sclerosis.

OBJECTIVES: Cardiopulmonary exercise test (CPET) is a widely used examination to predict the prognosis of many chronic pulmonary diseases, and it has also been tested in systemic sclerosis (SSc) with a focus on the development of pulmonary hypertension. CPET is a highly informative non-invasive tool that provides a more complex information than conventional lung function tests to predict the course of cardiopulmonary diseases, as it provides a general overview of the aerobic metabolism, influenced by pulmonary, cardiovascular and peripheral muscle function. The purpose of this investigation was to assess if the progression and the development of poor overall disease outcome in SSc can be predicted by this method. METHODS: Twenty-nine SSc patients were investigated prospectively with standard follow-up plus CPET for a mean of 3.7 years to match the results of conventional evaluation modalities and CPET. A composite end-point of several serious outcomes reflecting SSc-related vascular and cardiopulmonary damage was set up, and the predictive value of and correlations between the CPET parameters and resting lung function and echocardiography variables were assessed. RESULTS: None of the clinical parameters, resting lung function or echocardiographic test results proved to be predictive of the development of the endpoint of poor prognosis in this cohort. In contrast, several CPET parameters were found to discriminate between SSc patients with or without adverse outcome. The detection of desaturation (at any CPET test) was associated with a higher risk of poor prognosis (OR:5.265). VO2 and VE/VCO2 at baseline correlated with the annual decrease in FVC, anaerobic threshold with the development of digital ulcers, and VE/VO2 with the increase in pulmonary arterial pressure. CONCLUSIONS: Several CPET parameters obtained at the beginning of follow-up are informative of the appearance of various adverse end-points. CPET is a feasible examination in the care of SSc patients and provides excess information to current standard follow-up examinations.

Chlamydia pneumoniae Influence on Cytokine Production in Steroid-Resistant and Steroid-Sensitive Asthmatics.

Medications for asthma management consisting of inhaled corticosteroids act by controlling symptoms. However, some patients do not respond to steroid treatment due to immunological factors at the cytokine level. Chlamydia pneumoniae (C. pneumoniae) infection is strongly implicated in asthma pathogenesis, causing altered immune responses. We investigated the association of C. pneumoniae serostatus with the production of certain cytokines by peripheral blood mononuclear cells (PBMCs) of steroid-resistant and -sensitive asthmatic patients. Our most important findings are the following: In the case of C. pneumoniae seropositive patients we detected pronounced spontaneous interleukin (IL)-10 secretion and, in the case of steroid-resistant patients, IL-10 secretion was at a significantly higher level as compared with in-sensitive patients (p < 0.01). Furthermore, steroid-resistant seropositive patients produced a significantly higher level of IL-10 spontaneously and under antigen stimulation as compared with steroid-resistant seronegative individuals (p < 0.05). Concerning spontaneous TNF-α secretion by C. pneumoniae seropositive asthmatics, we observed that steroid-resistant patients produced significantly more of this cytokine than steroid-sensitive patients. In the steroid-resistant patients' sera, a remarkably high MMP-9 concentration was associated with C. pneumoniae seronegativity. Our study revealed that the differences in the cytokine production in steroid-sensitive and -resistant asthmatic patients can be influenced by their C. pneumoniae serostatus.

Determinants of CAT (COPD Assessment Test) scores in a population of patients with COPD in central and Eastern Europe: The POPE study.

BACKGROUND: The COPD Assessment Test (CAT) has been proposed to help guide therapy in chronic obstructive pulmonary disease (COPD). It is important to understand the distribution of scores in different COPD populations and their determinants. METHODS: The POPE study is an international, observational cross-sectional study of COPD subjects in 11 Central and Eastern European countries aimed at characterizing COPD phenotypes. Here we report the analysis of CAT scores with the objective of identifying their determinants, evaluating symptom load and investigating the distribution of scores among the participating countries. Additionally, we investigated the discrepancies between the CAT and modified Medical Research Council (mMRC) scores when used to classify patients according to the GOLD strategy. RESULTS: The study included 3452 patients (69.2% men, mean forced expiratory volume in 1 s (FEV1% predicted) 52.5%). The mean CAT score was 17.5 (SD = 7.8), ranging from 15.1 in Hungary to 21.2 in Bulgaria. Multiple linear regression analysis showed six variables significantly associated with CAT scores: depression, number of previous exacerbations, 6-min walking distance, FEV1(%), mMRC and country and explained 47.2% of the variance of CAT. According to either CAT or mMRC, up to 23.9% patients would be classified in different GOLD groups. CONCLUSIONS: The CAT score may be predicted by factors related to COPD severity, depression and exercise capacity, with significant differences in the distribution of CAT scores in different countries. According to our results CAT >10 is not equivalent to mMRC >2 for assessing symptom burden. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02119494.

Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

BACKGROUND: Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. METHODS: 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. CONCLUSIONS: Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609543.

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking.

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups.

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study.

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.

Relation of concavity in the expiratory flow-volume loop to dynamic hyperinflation during exercise in COPD.

Active expiration during exercise can increase intrathoracic pressure yielding concavity in the expiratory flow-volume loop in COPD. We investigated the relationship between this concavity and dynamic hyperinflation (DH). 17 COPD patients (FEV1: 38±10%pred, GOLD stage 3-4) and 12 healthy subjects performed cycle ergometer incremental exercise. Expiratory limb of the spontaneous flow-volume loop was analyzed breath-by-breath using a geometric approach (rectangular area ratio (RAR), Respir. Med., 104(3):389-96, 2010). RAR below 0.5 demonstrates expiratory limb concavity. DH was determined with serial inspiratory capacity maneuvers. 5 of 17 patients displayed little end-exercise concavity (RAR=0.52±0.04, group LCONC). 12 patients had concavity at rest and end-exercise RAR reached 0.40±0.03 (group HCONC). Healthy subjects showed no concavity. End-exercise RAR correlated with resting FEV1%pred (R2=0.81, P<0.05). Group HCONC, compared to groups LCONC and H, reached significantly lower work rate, minute ventilation, and more dyspnea. DH inversely correlated with RAR (R2=0.81, P<0.05). Detection of concavity in spontaneous flow-volume loops may help assess DH and exercise limitation in COPD.

[Interdisciplinary rehabilitation in patients with ankylosing spondylitis]. / Az interdiszciplináris rehabilitáció hatása spondylitis ankylopoeticában szenvedo betegekben.

INTRODUCTION: Complex pulmonary assessment related to respiratory manifestation in patients with ankylosing spondylitis may contribute to adaptation of an appropriate rehabilitation program. AIM: To examine the relationship between lung function, exercise physiological variables and change in quality of life after rehabilitation in patients with ankylosing spondylitis. METHOD: 5 patients in Seyfried's Stage 2 and 11 patients in Stage 3 underwent spinal physiotherapy, ultrasound, massage and paraffin Pack, 15 times each, followed by a high-intensity cycling 3 times a week for 8 weeks. The Bath Ankylosing Spondylitis Disease Activity and Bath Ankylosing Spondylitis Functional Indexes were recorded before and after rehabilitation. Lung function with exercise physiological variables were examined after rehabilitation. RESULTS: Both indexes showed a post-treatment significant improvement compared to the initial scores (p<0.05). These functional indices correlated with lung function at rest and physiological variables during exercise (p<0.05). CONCLUSIONS: Based on this study, it is possible that an initial pulmonary assessment may serve to develop a more effective program for ankylosing spondylitis. Orv. Hetil., 2016, 157(28), 1126-1132.

POPE study: rationale and methodology of a study to phenotype patients with COPD in Central and Eastern Europe.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE. METHODS/DESIGN: The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494. OUTCOMES: The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries. CONCLUSION: There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.

Pulmonary Arterial Pressure Response During Exercise in COPD: A Correlation with C-Reactive Protein (hsCRP).

BACKGROUND: The non-invasive assessment of pulmonary haemodynamics during exercise provides complementary data for the evaluation of exercise tolerance in patients with COPD. METHODS: Exercise echocardiography in the semi-supine position was performed in 27 patients with COPD (C) with a forced expiratory volume in one second (FEV1) of 36±12% predicted and 13 age and gender-matched non-COPD subjects (NC). COPD patients also underwent cardiopulmonary exercise testing with gas exchange detection (CPET). Furthermore, serum high sensitive C-reactive protein (hsCRP), a marker of systemic inflammation, was also measured. RESULTS: The maximal work rate (WRmax) and aerobic capacity (VO2peak) were significantly reduced (WRmax: 77±33 Watt, VO2peak: 50±14 %pred) in COPD. Pulmonary arterial systolic pressure (PAPs) was higher in COPD versus controls both at rest (39±5 vs. 31±2 mmHg, p<0.001), and at peak exercise (72±12 vs. 52±8 mmHg, p<0.001). In 19 (70%) COPD patients, the increase in PAPs was above 22 mmHg. The change in pressure (dPAPs) correlated with hsCRP (r2=0.53, p<0.0001) and forced vital capacity (FVC) (r2=0.18, p<0.001). CONCLUSION: PAPs at rest and during exercise were significantly higher in COPD patients and correlated with higher hsCRP. This may indicate a role for systemic inflammation and hyperinflation in the pulmonary vasculature in COPD. The study was registered at ClinicalTrials.gov webpage with NCT00949195 registration number.

Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer.

OBJECTIVE: This randomized phase II study assessed the efficacy and safety of obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to carboplatin/etoposide chemotherapy as initial treatment for extensive-stage small-cell lung cancer (ES-SCLC). MATERIALS AND METHODS: Chemotherapy-naïve subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) obatoclax for up to six cycles. Responders to CbEOb could receive maintenance obatoclax until disease progression. The primary endpoint was objective response rate (ORR). RESULTS: 155 subjects (median age 62, 58% male, 10% ECOG PS 2) were treated with CbEOb (n=77) or CbE (n=78); 65% and 59% of subjects, respectively, completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided p=0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% versus 68%; p=0.054). Median progression-free survival (PFS) and overall survival (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) with a nonsignificant hazard ratio for OS, 0.823; 1-sided p=0.121. Grade 3/4 adverse events (AEs) were primarily hematologic and similar in frequency between treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, transient, and did not require treatment discontinuation. CONCLUSION: Obatoclax was well tolerated when added to carboplatin/etoposide in first-line treatment of ES-SCLC, but failed to significantly improve ORR, PFS, or OS.

A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue Perfusion and Its Validation In Vitro and in Healthy Persons In Vivo and the Results of the Measurements in COPD Patients.

Introduction. Since its first publication in the medical literature, an extremely large number of references have demonstrated that the tonometric measurement of tissue perfusion is a reliable indicator of the actual condition of critically ill patients. Later a new method was developed by the introduction of sublingual tonometry for the determination of tissue perfusion. In comparison with gastric tonometry, the new method was simpler and could even be used in awake patients. Unfortunately, at present, because of severe failures of manufacturing, the device is withdrawn from commerce. Materials and Methods. In this study, we present a new method using a newly developed tool for the PslCO2 measurement in sublingual tonometry as well as the data for its validation in vitro and in vivo and the results of 25 volunteers and 54 COPD patients belonging to different GOLD groups at their hospitalization due to the acute exacerbation of the disease but already in a stable condition at the time of the examination. Results and Conclusion. The results of the performed examinations showed that the method is suitable for monitoring the actual condition of the patients by mucosal perfusion tonometry in the sublingual region.

Pulmonary epithelioid haemangioendothelioma studies in vitro and in vivo: new diagnostic and treatment methods.

BACKGROUND: Pulmonary epithelioid haemangioendothelioma is a rare endothelial tumour without standard treatment. For this reason, our aim is to present contemporary research outlining new therapeutic possibilities; thus in vitro and in vivo methods were combined. PATIENTS AND METHODS: Pulmonary epithelioid haemangioendothelioma was diagnosed in a 49-year-old female patient. A bronchial excision was obtained from a parenchymal lesion, and the excised sample was manipulated with in vitro-standardized experiments to support the diagnostic and therapeutic procedures. RESULTS: according to in vitro examination of tumour pulmonum and metastases from bone, carboplatin, docetaxel and pharmarubicin was the most effecient treatment modality. CONCLUSION: Currently, pulmonary epithelioid haemangioendothelioma does not have any standard treatment; the most efficient therapeutic regimen was gradually developed by combining in vitro and in vivo methods, which proved to be an efficient therapeutic modality hitherto.

A survey of the burden of allergic rhinitis in Hungary from a specialist's perspective.

BACKGROUND: The casual and severity distribution of allergic rhinitis (AR) in Hungary is unknown.The aim of this survey was to evaluate symptom perception, disease severity, concomitant asthma frequency and the impact of AR on everyday life activities in a cross-sectional, multicenter study in Hungary under the supervision of Hungarian Respiratory Society. METHODS: Data were recorded by 933 AR patients (65.93% women) and their treating specialists. The perceptions of patients regarding the symptoms (nasal, ocular and others) of AR and its severity, together with its impact on everyday life were assessed. Physicians recorded data regarding the diagnosis and severity of AR, and comorbidities. RESULTS: 52.5% of patients suffered from seasonal AR, 35.1% from perennial AR. A large proportion of patients had moderate to severe disease (MS-AR) (57.34%), persistent disease (98.0%) and concomitant asthma (53.32% in the mild, 57.52% in the MS-AR group). MS-AR was more frequent among women. Despite the treatment used, in MS-AR the proportions of patients reporting moderate to severe rhinorrhoea, nasal obstruction, ocular itching/redness, watering, itchy throat and sneezing were as high as 52.0%, 54.0%, 33.8%, 26.5%, 44.0% and 31.2%, respectively. Overall, there was a poor agreement between disease severity reported by patients and specialists. The adherence to oral antihistamines and intranasal corticosteroids was found to be between 50 and 65%; mostly depending on the dosage form. CONCLUSIONS: AR remains a significant health problem in Hungary because of the burden of symptoms, high rate of concomitant asthma and the significant proportion of MS-AR affecting general well being.

[Primary pulmonary epitheloid haemangioendothelioma]. / Primer pulmonalis epitheloid haemangioendothelioma.

A 49-year-old female patient was admitted in July 2009 because of cough, weight loss and effort dyspnoe. Chest X-ray and CT showed multiple bilateral nodules which have been identified earlier and these nodules were unchanged. However, there was a new parenchymal lesion in the right upper lobe, and new right hilar and mediastinal lymphadenomegaly was also found. Sample was taken by bronchoscope and the pathological diagnosis was pulmonary epitheloid haemangioendothelioma. This rare endothelial tumor usually affects middle-aged patients with a female predominance and it presents with chest pain, effort dyspnoe, cough, sputum, or it may remain asymptomatic. Multiple bilateral nodules are usually detected by radiologic examination. The diagnosis of this tumor is often challenging and, because of its rarity, it does not have any standard therapeutic regimen. Treatment can be surgery, chemo-, radio-, hormone- or immunotherapy. In order to find the most effective anticancer treatment, authors performed in vitro studies. On the basis of the results, chemotherapy was initiated which resulted in a partial regression.

Asthma and gastroesophageal reflux: clinical evaluation of esophago-bronchial reflex and proximal reflux.

AIMS: To evaluate the prevalence of proximal reflux and esophago-bronchial reflex (EBR) in patients with asthma, and to compare the symptom spectrum, esophageal acid sensitivity, pH monitoring, and the endoscopic and manometric parameters of EBR-positive and -negative patients with asthma. PATIENTS AND METHODS: Forty-three consecutive patients with recent diagnoses of asthma and 20 patients with chronic cough but without asthma were prospectively submitted to detailed reflux and respiratory symptom analysis, upper gastrointestinal endoscopy, esophageal manometry, Bernstein test and double-channel intra-esophageal pH monitoring. The presence of EBR was studied by combined esophageal acid (0.1 N HCl) perfusion and methacholine test. RESULTS: Patients with asthma had significantly more proximal acid reflux than controls. Patients with EBR positivity were more likely to have an acid-sensitive esophagus and had more acid reflux especially in the supine period at the distal measurement point. Other parameters were similar. CONCLUSIONS: Patients with asthma had significantly more proximal acid reflux than those with chronic cough. The combination of the methacholine test with esophageal acid perfusion is able to establish the presence of EBR, however prospective therapeutic trials are needed to confirm its clinical value. The increased amount of acid reflux during the supine period in patients with EBR may indicate a role for appropriate nighttime acid suppressive therapy.

Supervised high intensity continuous and interval training vs. self-paced training in COPD.

BACKGROUND: Endurance training is an effective component of pulmonary rehabilitation in COPD. Controversy exists regarding whether different modalities of supervised exercise training (continuous (C) or interval (I)) or self-paced (S) programs are equally beneficial. METHODS: Seventy-one patients with COPD (average FEV(1)=55% predicted) were assigned to 8 weeks of C, I or S training, 45 min/session, 3 times/week. Group C (n=22) exercised at 80% of pre-training peak work rate in an incremental cycle ergometer test. In group I (n=17), training consisted of 30 min of cycling 2 min at 90% followed by 1 min at 50% peak work rate bracketed by 7.5 min at 50% peak work rate. The S group (n=32) was instructed to cycle, climb stairs and walk in their home with the same periodicity and time intervals. RESULTS: Improvement in incremental test peak work rate was significant in both C and I groups, but not in S. Peak oxygen uptake and lactic acidosis threshold improved significantly in the supervised groups, but differences among groups did not achieve significance. Scores in an activity questionnaire improved in all groups without significant differences among groups. CONCLUSIONS: In COPD patients, continuous and interval training have similar physiologic effects; by some measures of endurance exercise performance, they are superior to self-paced training. However, all were effective in improving patient-perceived activity.