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1.
J Autoimmun ; 140: 103118, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37826919

RESUMO

BACKGROUND: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease. OBJECTIVE: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease. METHODS: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells. RESULTS: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells. CONCLUSIONS: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance.

2.
Respiration ; 102(10): 863-878, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37769646

RESUMO

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Antiasmáticos/uso terapêutico , Suíça/epidemiologia , Administração por Inalação , Asma/tratamento farmacológico , Asma/epidemiologia , Corticosteroides/uso terapêutico , Esteroides/uso terapêutico , Produtos Biológicos/uso terapêutico
3.
Rev Med Suisse ; 19(840): 1627-1633, 2023 Sep 06.
Artigo em Francês | MEDLINE | ID: mdl-37671764

RESUMO

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.


La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.


Assuntos
Clínicos Gerais , Doença Pulmonar Obstrutiva Crônica , Humanos , Exercício Físico , Doenças Negligenciadas , Pneumologistas
4.
Praxis (Bern 1994) ; 112(7-8): 403-412, 2023 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-37282526

RESUMO

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncodilatadores/uso terapêutico , Quimioterapia Combinada , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Corticosteroides/uso terapêutico
5.
Respir Med ; 206: 107067, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563609

RESUMO

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers.


Assuntos
Antiasmáticos , Asma , Eosinofilia Pulmonar , Adulto , Humanos , Asma/complicações , Asma/epidemiologia , Asma/tratamento farmacológico , Eosinofilia Pulmonar/complicações , Antiasmáticos/uso terapêutico
6.
Am J Respir Crit Care Med ; 207(1): 38-49, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926164

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 BAL fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on BAL fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and Main Results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19 but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA autoantibodies against pulmonary surfactant proteins B and C and that these autoantibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation.


Assuntos
COVID-19 , Surfactantes Pulmonares , Humanos , Surfactantes Pulmonares/metabolismo , Líquido da Lavagem Broncoalveolar/química , Tensoativos , Autoanticorpos , Imunoglobulina A
7.
Rev Med Suisse ; 18(787): 1269-1274, 2022 Jun 22.
Artigo em Francês | MEDLINE | ID: mdl-35735152

RESUMO

For general practitioners there have been important novelties in the treatment of asthma due to recent modifications of the international guidelines from Global Initiative for Asthma (GINA). In Step 1, use of short-acting beta2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as controller is no longer recommended for lack of efficacy and safety reasons. Instead, low dose ICS-formoterol as needed is recommended. In Step 5, in patients with severe uncontrolled asthma GINA recommends targeted biologic therapies like interleukin antibodies. Asthma patients presenting simultaneously with symptoms of chronic obstructive pulmonary disease (COPD) should receive treatment containing ICS. Independent of the current corona pandemic, GINA recommendations stay in place.


Les nouvelles recommandations GINA (Global Initiative for Asthma) modifient radicalement la prise en charge des patients asthmatiques pour le médecin de premier recours. Dans l'asthme léger (palier 1 GINA), les bêta2-agonistes à courte durée d'action (SABA) seuls comme traitement de secours ne sont plus recommandés au profit d'une association de corticostéroïdes inhalés (CSI) faiblement dosés avec un bronchodilatateur à longue durée d'action à début d'action rapide (formotérol). Dans l'asthme sévère non contrôlé (palier 5 GINA), l'objectif est d'éviter la corticothérapie orale au profit de thérapies biologiques ciblées (par exemple, anticorps anti-interleukine). Un traitement contenant des CSI doit être maintenu chez les asthmatiques même si une BPCO est associée. Les recommandations GINA ne sont pas modifiées par les conditions actuelles de pandémie.


Assuntos
Antiasmáticos , Asma , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Fumarato de Formoterol/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
8.
Infection ; 50(3): 783-790, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35426564

RESUMO

PURPOSE: COVID-19 patients on anti-CD20 treatment can suffer a delayed viral clearance and worse clinical outcome. We aim to present our experience with remdesivir treatment in anti-CD20-treated patients with prolonged symptoms, a patient population for which no data from randomized controlled trials are available. METHODS: From the beginning of the pandemic until February 2021, we included all consecutive patients from our healthcare network on anti-CD20 treatment with prolonged COVID-19 symptoms, who received remdesivir. Patient informed consent was gathered and patients' charts were reviewed to collect baseline data, COVID-19 history including time of symptom onset, diagnosis, data on treatment and disease course. Patients or their next of kin were contacted in March 2022 to assess long-term outcomes. RESULTS: We included 11 patients, who received remdesivir at a median of 33 days after diagnosis. Eight patients showed clinical improvement along with reductions in viral loads, one patient with relapsing infection recovered after administration of convalescent plasma, and two patients died. No clinical relapses were reported (median follow-up 13 months), while follow-up PCRs were not performed. One patient died of underlying malignancy 8 months after recovery from COVID-19. CONCLUSIONS: We observed a benefit of antiviral therapy in a majority of COVID-19 patients on anti-CD20 treatment, without any clinical relapses in the 1-year follow-up. Although these data suggest that remdesivir might be a promising management option in patients with delayed viral clearance, the lack of a control group is an important limitation of the study design. TRIAL REGISTRATION: Ethikkommission Ostschweiz, Scheibenackerstrasse 4, CH-9000 St. Gallen approved this case series. Project-ID 2021-00349 EKOS 21/027.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , COVID-19/terapia , Humanos , Imunização Passiva , Recidiva , SARS-CoV-2 , Resultado do Tratamento , Soroterapia para COVID-19
9.
Praxis (Bern 1994) ; 110(16): 967-974, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-34704824

RESUMO

Novelties in the Treatment of Asthma Abstract. For general practitioners there have been important novelties in the treatment of asthma due to recent modifications of the international guidelines from Global Initiative for Asthma (GINA). Step 1 no longer recommends the use of short-acting ß2-agonists (SABA) without concomitant inhaled corticosteroids (ICS) as a controller because of the lack of efficacy and for safety reasons. Instead, low dose ICS-formoterol as needed is recommended. GINA step 5 recommends targeted biologic therapies like interleukin antibodies in patients with severe uncontrolled asthma. Asthma patients presenting simultaneously with symptoms of chronic obstructive pulmonary disease (COPD) should receive treatment containing ICS. Independent of the current corona pandemic, GINA recommendations stay in place. Recent data on prescriptions of SABA and oral corticosteroids (OCS) in Switzerland indicate that they still play an important role in asthma management and that GINA recommendations have not yet been sufficiently implemented into practice.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides/uso terapêutico , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Fumarato de Formoterol/uso terapêutico , Humanos
10.
Int J Chron Obstruct Pulmon Dis ; 16: 2487-2500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511893

RESUMO

BACKGROUND: Airflow reversibility criteria in COPD are still debated - especially in situations of co-existing COPD and asthma. Bronchodilator response (BDR) is usually assessed by spirometric parameters. Changes assessed by plethysmographic parameters such as the effective, specific airway conductance (sGeff), and changes in end-expiratory resting level at functional residual capacity (FRCpleth) are rarely appreciated. We aimed to assess BDR by spirometric and concomitantly measured plethysmographic parameters. Moreover, BDR on the specific aerodynamic work of breathing (sWOB) was evaluated. METHODS: From databases of 3 pulmonary centers, BDR to 200 g salbutamol was retrospectively evaluated by spirometric (∆FEV1 and ∆FEF25-75), and plethysmographic (∆sGeff, ∆FRCpleth, and ∆sWOB) parameters in a total of 843 patients diagnosed as COPD (478 = 57%), asthma-COPD-overlap (ACO) (139 = 17%), or asthma (226 = 27%), encountering 1686 BDR-measurement-sets (COPD n = 958; ACO n = 276; asthma n = 452). RESULTS: Evaluating z-score improvement taking into consideration the whole pre-test z-score range, highest BDR was achieved by combining ∆sGeff and ∆FRC detecting BDR in 62.2% (asthma: 71.4%; ACO: 56.7%; COPD: 59.8%), by ∆sGeff in 53.4% (asthma: 69.1%; ACO: 51.6%; COPD: 47.4%), whereas ∆FEV1 only distinguished in 10.6% (asthma: 21.8%; ACO: 18.6%; COPD: 4.2%). Remarkably, ∆sWOB detected BDR in 49.4% (asthma: 76.2%; ACO: 47.8%; COPD: 46.9%). CONCLUSION: BDR largely depends on the pre-test functional severity and, therefore, should be evaluated in relation to the pre-test conditions expressed as ∆z-scores, considering changes in airway dynamics, changes in static lung volumes and changes in small airway function. Plethysmographic parameters demonstrated BDR at a significant higher rate than spirometric parameters.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/diagnóstico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos , Espirometria
12.
Clin Infect Dis ; 73(9): e2869-e2874, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32997739

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL). METHODS: In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020. RESULTS: Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti-beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS: Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.


Assuntos
COVID-19 , Anticorpos Antifosfolipídeos , Humanos , Imunoglobulina A , Estudos Retrospectivos , SARS-CoV-2
13.
PLoS One ; 12(11): e0187548, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29117249

RESUMO

6-min walk tests (6MWT) are routinely performed in patients with chronic obstructive pulmonary disease (COPD). Oxygen uptake ([Formula: see text]) kinetics during 6MWT can be modeled and derived parameters provide indicators of patients' exercise capacity. Post-exercise [Formula: see text] recovery also provides important parameters of patients' fitness which has not been extensively investigated in COPD. Several nonlinear regression models with different underlying biological assumptions may be suitable for describing recovery kinetics. Multimodel inference (model averaging) can then be used to capture the uncertainty in considering several models. Our aim was to apply multimodel inference in order to better understand the physiological underpinnings of [Formula: see text] recovery after 6MWT in patients with COPD. 61 patients with COPD (stages 2 to 4) were included in this study. Oxygen kinetics during 6MWT were modeled using nonlinear regression. Three statistical approaches (mixed-effects, meta-analysis and weighted regression) were compared in order to summarize estimates obtained from multiple kinetics. The recovery phase was modeled using 3 distinct equations (log-logistic, Weibull 1 and Weibull 2). Three models were fitted to the set of 61 kinetics. A significant model-averaged difference of 40.39 sec (SE = 17.1) in the time to half decrease of [Formula: see text] level ([Formula: see text]) was found between stage 2 and 4 (p = 0.0178). In addition, the Weibull 1 model characterized by a steeper decrease at the beginning of the recovery phase showed some improvement of goodness of fit when fitted to the kinetics of patients with stage 2 COPD in comparison with the 2 other models. Multimodel inference was successfully used to model [Formula: see text] recovery after 6MWT in patients with COPD. Significant model-averaged differences in [Formula: see text] were found between moderate and very severe COPD patients. Furthermore, specific patterns of [Formula: see text] recovery could be identified across COPD stages.


Assuntos
Modelos Biológicos , Oxigênio/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Teste de Caminhada , Humanos , Cinética , Testes de Função Respiratória , Fatores de Tempo
14.
Respiration ; 92(6): 371-379, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27825150

RESUMO

BACKGROUND: There is a growing interest in exercise parameters capable of objectively evaluating the functional capacity of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The purpose of the present study was to analyze breath-by-breath cardiopulmonary and gas exchange recovery responses of patients with COPD after a 6-minute walk test (6MWT). METHODS: Oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during and after a 6MWT. Recovery kinetics were modelled using a 4-parameter nonlinear logistic model. Multiple linear regression was performed to assess the association between the half-time of recovery of oxygen consumption (T1/2 VO2) and exercise capacity (6-minute walking distance, 6MWD). RESULTS: Sixty-nine patients with COPD (28 females) with a mean age of 65 ± 10 years took part in the study. After adjustment for covariates (body mass index, forced expiratory volume in 1 s, forced vital capacity, and age), T1/2 VO2 was significantly associated with 6MWD (p = 0.002). CONCLUSIONS: T1/2 VO2 can be used to reflect exercise capacity in patients with COPD. As T1/2 VO2 mostly depends on the rate of increase in pulmonary blood flow, the results of the present study underline the importance of cardiocirculatory impairment for exercise intolerance in patients with COPD.


Assuntos
Consumo de Oxigênio , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Troca Gasosa Pulmonar , Teste de Caminhada , Idoso , Testes Respiratórios , Estudos Transversais , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Cinética , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pletismografia Total , Capacidade de Difusão Pulmonar , Capacidade Vital
15.
BMC Pulm Med ; 14: 167, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25355483

RESUMO

BACKGROUND: The 6-Minute Walk Test (6MWT) is representative of daily-life activities and reflects the functional capacity of patients. The change of oxygen uptake (VO2) in the initial phase of low-intensity exercise (VO2 kinetics) can be used to assess submaximal exercise performance of patients.The objective of the following study was to analyse VO2 kinetics in patients with different pulmonary and cardiovascular diseases. In addition, we investigated the extent to which VO2 kinetics at the onset of the 6MWT were associated with exercise capacity, morbidity and mortality. METHODS: VO2 kinetics of 204 patients and 16 healthy controls were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT. A new mean response time (MRT) index (wMRT) was developed to quantify VO2 kinetics by correcting MRT for work rate. The differences in wMRT between disease categories as well as the association between wMRT and patients' exercise capacity and outcome - time to hospitalization/death- were tested. RESULTS: The assessment of a robust wMRT was feasible in 86% (244/284) patients. wMRT was increased in patients compared to healthy controls (p <0.001). wMRT was largest in patients with pulmonary arterial hypertension (PAH). There were significant associations between wMRT and exercise capacity in all patients. High wMRT was found to be associated with a high rate of death and re-hospitalization in patients with CHF (p = 0.024). In patients with pulmonary diseases and pulmonary hypertension wMRT was not associated with outcome (p = 0.952). CONCLUSIONS: Submaximal exercise performance of patients is reduced. O2 kinetics at the onset of exercise are associated with exercise capacity in all patients. wMRT was found to be an important prognostic factor in patients with congestive heart failure (CHF), but not with pulmonary diseases.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Consumo de Oxigênio/fisiologia , Oxigênio/farmacocinética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Caminhada/fisiologia , Adulto , Idoso , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Insuficiência Cardíaca/mortalidade , Frequência Cardíaca , Hospitalização , Humanos , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Esforço Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Troca Gasosa Pulmonar , Taxa Respiratória , Telemetria , Volume de Ventilação Pulmonar
16.
BMC Bioinformatics ; 14: 178, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23742070

RESUMO

BACKGROUND: Interpretation of gene expression microarray data in the light of external information on both columns and rows (experimental variables and gene annotations) facilitates the extraction of pertinent information hidden in these complex data. Biologists classically interpret genes of interest after retrieving functional information from a subset of genes of interest. Transcription factors play an important role in orchestrating the regulation of gene expression. Their activity can be deduced by examining the presence of putative transcription factors binding sites in the gene promoter regions. RESULTS: In this paper we present the multivariate statistical method RLQ which aims to analyze microarray data where additional information is available on both genes and samples. As an illustrative example, we applied RLQ methodology to analyze transcription factor activity associated with the time-course effect of steroids on the growth of primary human lung fibroblasts. RLQ could successfully predict transcription factor activity, and could integrate various other sources of external information in the main frame of the analysis. The approach was validated by means of alternative statistical methods and biological validation. CONCLUSIONS: RLQ provides an efficient way of extracting and visualizing structures present in a gene expression dataset by directly modeling the link between experimental variables and gene annotations.


Assuntos
Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores de Transcrição/metabolismo , Sítios de Ligação , Proliferação de Células/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Pulmão/citologia , Anotação de Sequência Molecular , Furoato de Mometasona , Análise Multivariada , Pregnadienodiois/farmacologia
17.
J Neurol ; 260(9): 2279-85, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23749294

RESUMO

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored.


Assuntos
Terapia de Reposição de Enzimas/economia , Glucana 1,4-alfa-Glucosidase/economia , Doença de Depósito de Glicogênio Tipo II/economia , Seguro de Serviços Farmacêuticos/economia , Doenças Raras/economia , Idade de Início , Idoso , Efeitos Psicossociais da Doença , Feminino , Glucana 1,4-alfa-Glucosidase/uso terapêutico , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Guias como Assunto , Humanos , Honorários por Prescrição de Medicamentos , Doenças Raras/tratamento farmacológico , Suíça
18.
Respiration ; 82(2): 193-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21474919

RESUMO

Parapneumonic effusions or empyemas are frequently seen in patients with lower respiratory tract infections. The condition is associated with significant morbidity and mortality. Since Gram stains and bacterial cultures are usually negative, treatment focuses on empiric antibiotic treatment and chest tube drainage. The role of intrapleural fibrinolytics is still a matter of debate. Medical thoracoscopy is a simple and effective therapeutic alternative associated with better outcome and fewer complications than conservative treatment. Furthermore, it can be performed in analgo-sedation in a bronchoscopy suite. Video-assisted thoracic surgery carries the advantage of providing optimal visibility of the pleural cavity, thus allowing better debridement. Thoracotomy is the treatment of choice when thoracoscopic cleaning is not satisfactory.


Assuntos
Empiema Pleural/cirurgia , Derrame Pleural/cirurgia , Cirurgia Torácica Vídeoassistida , Antibacterianos/uso terapêutico , Drenagem/métodos , Humanos , Derrame Pleural/etiologia , Guias de Prática Clínica como Assunto , Infecções Respiratórias/complicações , Medição de Risco
19.
Respiration ; 80(5): 410-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20699610

RESUMO

BACKGROUND: The 6-min walk test (6MWT) is frequently used to assess overall cardiopulmonary fitness and to predict outcome, but it yields little diagnostic information. Portable telemetric devices allow performing the 6MWT with real-time cardiopulmonary monitoring. OBJECTIVES: The study was designed to analyze feasibility, safety and clinical usefulness of a mobile cardiopulmonary monitoring (MOB)-enhanced 6MWT. METHODS: From August 2003 to June 2007, 261 consecutive patients with chronic lung and/or heart disease as well as healthy controls underwent MOB-enhanced 6MWTs. A subgroup of 33 individuals had the test done with and without cardiopulmonary monitoring on independent days. RESULTS: No test-related adverse events occurred throughout the study. Whether the 6MWT was done without or with cardiopulmonary monitoring (n = 33) did not significantly influence the walking distance (WD: 528 ± 183 vs. 525 ± 192 m; nonsignificant). Fifty-nine percent (155/261) of the patients fulfilled the maximal test criteria. Distinct disease-specific exercise response patterns as well as treatable co-pathologies were observed. The validity of response patterns was better in case of a maximal test. CONCLUSION: An MOB-enhanced 6MWT is feasible within daily routine and safe in patients with various diseases. It does not negatively affect WD. MOB is a valuable tool to identify factors limiting exercise in patients irrespective of their underlying disease.


Assuntos
Eletrocardiografia Ambulatorial/instrumentação , Teste de Esforço , Espirometria/instrumentação , Telemetria , Adulto , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Cardiopatias/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Pneumopatias/fisiopatologia , Masculino , Máscaras , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia
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