RESUMO
The prevalence of pulmonary hypertension (PH) in the general chronic obstructive pulmonary disease (COPD) population is undefined because stable COPD patients do not routinely undergo screening echocardiogram and right heart catheterization. Most studies published on this topic are focused on a highly selected group of patients with moderate to severe disease awaiting lung transplantation, since hemodynamic data from cardiac catheterization are part of the standard transplant evaluation. In a very recent article, Hurdman et al. studied the characteristics and outcomes, with a particular focus on mortality, of extensively phenotyped, consecutive patients with PH-COPD over a 9-year period. This article offers the opportunity to update the role of PH in COPD as a timer to propose lung transplantation, based on solid literature data on survival, and to select the best procedure (single or double lung transplant), since the outcome indexes based on the old GOLD classification according to FEV1 (1-4) and the new GOLD classification (A-D) have failed in purpose to define the correct timing, due to the lack of functional (6 minutes walking test) and nutritional (Body Mass Index) data. After a revision of available literature including the recent paper of Hurdman et al. we conclude that the timing for lung transplantation is easy to manage in case of severe PH-COPD. On the other hand mild and moderate PH-COPD are still object of debate for therapy, procedure timing and choice and rehabilitation. In other words, we have some confirms for a little percentage of patients, whilst many doubts still exist for the rest.
RESUMO
STUDY OBJECTIVES: (1) To define the incidence and natural history of Aspergillus colonization and infection in lung transplant recipients, and (2) to assess the impact of prophylaxis, surveillance, and therapy on the incidence and outcome of the disease. DESIGN: Retrospective review of 133 consecutive single or bilateral lung transplantations performed at a single institution, and review of the published literature. RESULTS: Airway colonization, isolated tracheobronchitis, and invasive pneumonia due to Aspergillus species occurred in 29%, 5%, and 8% of our series, and in 26%, 4%, and 5% of the pooled published data (all series, including ours), respectively. Greater than 50% of all diagnoses were made in the first 6 months after transplantation in both our series and the published literature. Incidence of progression from airway colonization to invasive disease was 1 in 38 in our series and 3 of 97 (3%) in the pooled published data. In patients with isolated tracheobronchitis, all 6 patients in our series and 41 of 50 patients (82%) in all published series, including ours, responded to antifungal therapy and/or surgical debridement. Among patients with invasive pneumonia or disseminated disease, however, 5 of 10 patients in our series and 26 of 64 patients (41%) in the pooled series survived their infection. CONCLUSIONS: The role of antifungal therapy in Aspergillus airway colonization in lung transplant recipients is unclear. Data support a strategy of scheduled screening bronchoscopy followed by aggressive treatment for isolated Aspergillus tracheobronchitis in lung transplant recipients.
Assuntos
Aspergilose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Transplante de Pulmão , Infecções Oportunistas/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Aspergilose/epidemiologia , Bronquite/diagnóstico , Bronquite/epidemiologia , Broncoscopia , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Pneumopatias Fúngicas/epidemiologia , Masculino , Michigan , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Fatores de RiscoRESUMO
Primary pulmonary hypertension (PPH) is essentially a diagnosis of exclusion and usually is made late because of the nonspecific nature of the early signs and symptoms. Echocardiography is a key screening test in the diagnostic algorithm of patients with suspected PPH. The purpose of this study was to define the echocardiographic Doppler features in patients with PPH at the time of diagnosis. From 1992 to 1997, 51 patients were diagnosed with PPH at our institution. All underwent a standardized transthoracic echocardiographic examination, including a contrast study and transthoracic echocardiographic examination if indicated. Pulmonary artery systolic pressure was calculated from the tricuspid regurgitation jet. The majority of patients had pulmonary artery systolic pressure greater than 60 mm Hg (96%) associated with systolic flattening of the interventricular septum (90%), enlarged right atrium (92%) and ventricle (98%), and reduced right ventricular systolic function (76%). There was an increase in the interventricular septal thickness (>1.2 cm) in 21 (43%) of 49 patients, accompanied by a septal/posterior wall ratio greater than 1.3 in 11 (22%) of 49. Although a reduction in both left ventricular systolic and diastolic volumes was noted, global left ventricular systolic function was preserved in all patients. Mitral E/A ratio was less than 0.7 in 7 (22%) patients studied. Color Doppler revealed moderate to severe tricuspid regurgitation and pulmonic insufficiency in 41 (80%) of 51 and 16 (31%) of 51 of cases, respectively. Pericardial effusion (7 small and 1 moderate) and patent foramen ovale (n = 12) were also frequently detected. At the time of initial diagnosis, PPH is associated with secondary cardiac abnormalities in the majority of patients.
Assuntos
Ecocardiografia , Hipertensão Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Cateterismo Cardíaco , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Sístole , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Função VentricularRESUMO
We investigated the PCNA immunoreactivity in 35 specimens of malignant mesothelioma and 20 specimens of mesothelial hyperplasia in order to evaluate the usefulness of this parameter in differentiating between these two mesothelial proliferations, and to determine whether PCNA has any prognostic significance in mesotheliomas. Eleven of the 35 investigated malignant mesotheliomas displayed up to 25% of positive cells for PCNA expression. The remaining 24 specimens showed high percentages of positive cells ranging from 26% to 95%. All specimens of reactive hyperplasia had less than 25% of PCNA positive cells. The difference between malignant mesothelioma and mesothelial hyperplasia for PCNA immunoreactivity was statistically significant (p < 0.01). A positive relationship was also found between PCNA expression level and the overall survival of those affected by malignant mesothelioma (p = 0.0032). Our results suggest on important role for PCNA in differentiating diagnosis of mesothelial proliferations. It remains unclear whether PCNA expression truly correlates with the proliferation rate of the malignant mesotheliomas and with the overall survival of patients affected by this neoplasm.
Assuntos
Biomarcadores Tumorais/análise , Mesotelioma/química , Proteínas de Neoplasias/análise , Antígeno Nuclear de Célula em Proliferação/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, a plasma cell dyscrasia associated with pulmonary hypertension, has been treated in the past with anticytokine strategies with a poor outcome. A patient is described who had POEMS syndrome with precapillary pulmonary hypertension and Raynaud's phenomenon, and who responded well to a short course of corticosteroids and long term nifedipine. POEMS syndrome, like anorexigens, cocaine, portal hypertension and human immunodeficiency virus infection, may be another trigger for the pulmonary vascular occlusive process found in primary pulmonary hypertension.
Assuntos
Hipertensão Pulmonar/etiologia , Síndrome POEMS/complicações , Corticosteroides/administração & dosagem , Diuréticos/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Síndrome POEMS/diagnóstico , Síndrome POEMS/tratamento farmacológico , Doença de Raynaud/complicações , Doença de Raynaud/diagnóstico , Doença de Raynaud/tratamento farmacológico , Indução de Remissão , Fatores de TempoRESUMO
A whole range of otolaryngeal manifestations may occur as complications or represent the first symptom and sign of a variety of systemic diseases. Otolaryngologists are often the first physicians to recognize that otolaryngeal abnormalities are symptomatic of a broader disease and mandate a systemic approach to the problem. In the present study, the authors focus primarily on ear, nose and throat manifestations that may occur in the context of systemic diseases, discussing clinical manifestations and reviewing the salient histologic, laboratory, and serologic features.
Assuntos
Granulomatose com Poliangiite/complicações , Histiocitose de Células de Langerhans/complicações , Lúpus Eritematoso Sistêmico/complicações , Otorrinolaringopatias/complicações , Sarcoidose/complicações , HumanosRESUMO
Improvements in biological research and the development of new techniques for human health protection require animal experimentation of various species. In particular, animal models are always necessary to test new therapies for the treatment of various human diseases. The latest advances in molecular biology involving genetic modification are aimed at developing new animal models of human diseases that are not present in spontaneous murine broods or obtainable with other experimental manipulations. Transgenic techniques and, in particular, the possibility to directly modify specific genetic information in the experimental animal have led to the acquisition of important knowledge on the physiologic functions of many proteins and their function in the course of various diseases. The advent of new transgenic animals is opening up new and interesting frontiers, full of hope and opportunity, for the research into pulmonary diseases. New advances in cystic fibrosis, emphysema, and pulmonary fibrosis have been made through the study of a large number of proteins implicated in the complex of acute and chronic inflammatory processes of lung parenchyma, which are responsible for permanent changes in organ structure and function. Recent studies carried out on murine inbred strains have yielded significant new data on the multifactor origin of pulmonary disease, because of their correlation with the major histocompatibility complex (H2 in mice) or through the different genetic map of the strains. Today it is possible to outweigh or potentiate the function and expression of some genes, obtaining a deficit or abundance, respectively, of specific proteins. These techniques have permitted and will continue to permit the development of new models of human disease, leading to further therapeutic advances as a consequence.
Assuntos
Animais Geneticamente Modificados , Pneumopatias , Modelos Anatômicos , Animais , Citocinas/fisiologia , Pneumopatias/fisiopatologiaRESUMO
The effects of environmental pollutants on human health and, in particular, on the respiratory apparatus, can be studied fundamentally by means of epidemiological and controlled exposure studies. One epidemiological study has reported the results of research which compared pulmonary function in adults with the average annual concentration of major pollutants in 8 geographical areas of Switzerland; the results demonstrated a direct relationship between atmospheric pollution and a worsening of pulmonary function. Controlled exposure studies, on the other hand, document the effects of specific air pollutants. Ozone (O3) is a secondary pollutant produced in the atmosphere by photochemical reactions which exerts a potent antioxidant and peroxidant action on biomolecules, whether intra or extracellular, with the production of free radicals. Nitrogen dioxide (NO2) is found mainly indoors due to its being a product of combustion of kitchen gas--it possesses low reactivity and low solubility that allows its penetration to the periphery of the lungs; the harmful mechanisms induced by NO2 are not well understood and could differ from those of O3. Sulphur dioxide (SO2) is found above all outdoors and is documented to affect the respiratory function of asthmatic subjects at concentrations above 1 part per million (ppm) while it has a doubtful effect on healthy subjects. Suspended particulate matter (SPM) is one of the major pollutants present in the air that comes mainly from vehicle exhausts, especially diesel models. Although the epidemiological data indicates a close relationship with both cardiac and respiratory pathology, the biological mechanisms by which it exerts its toxicity are still not well established. The great variability in individual response to pollutants suggests the need for further sensitivity tests to be carried out: it is of importance to identify specific genes with a stabilising role in cellular protection against oxidative stress, that influence the production of chemical mediators of inflammation.
Assuntos
Poluentes Atmosféricos/farmacologia , Sistema Respiratório/efeitos dos fármacos , Ambiente Controlado , Humanos , Dióxido de Nitrogênio/farmacologia , Projetos de Pesquisa , Dióxido de Enxofre/farmacologiaRESUMO
Pulmonary epithelioid haemangioendothelioma (PEH) is a rare lung tumour of vascular origin and low-grade malignancy that affects various organs: liver, central nervous system, lung, etc. A rare malignant case of PEH is described. The cryptic clinical appearance and the nonspecific results of radiography and haematological tests caused great difficulty in arriving at a definite diagnosis. Histological analysis and immunohistochemical detection of CD31+ (a membrane receptor and a sensitive and specific marker for vascular lesions), on open lung biopsy, enabled the correct diagnosis to be made.
Assuntos
Hemangioendotelioma Epitelioide/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adulto , Biópsia , Diagnóstico Diferencial , Evolução Fatal , Hemangioendotelioma Epitelioide/patologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Tomografia Computadorizada por Raios XRESUMO
Behçet's disease (BD) is a chronic multisystem vasculitis, affecting many organs and the vascular system, of unknown aetiology. Eyes, skin, joints, the oral cavity, the central nervous system, and, less frequently, heart, lung, kidney, the genital system and the gastrointestinal tract can be involved. Intrathoracic manifestations of BD consist mainly of thromboembolism of the superior vena cava and/or other mediastinal veins; aneurysms of the aorta and pulmonary arteries; pulmonary infarct and haemorrhage; pleural effusion; and, rarely, myocardial and/or hilar lymphoid involvement. In the present case, the patient presented with BD with an asymptomatic subpleural lung mass and bilateral pulmonary artery enlargement. The patient was treated with a combination of surgical and medical therapy with complete resolution of the lung involvement and without any parenchymal relapses after an 8-month follow-up.
Assuntos
Síndrome de Behçet/complicações , Pneumopatias/etiologia , Síndrome de Behçet/diagnóstico , Humanos , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Pleura/patologia , Doenças Pleurais/diagnóstico , Doenças Pleurais/etiologiaRESUMO
Clinical and experimental investigations indicate that respiratory viral infections are important triggers for asthma attacks. Viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. Human Rhinovirus (HRV) has been implicated as the most common virus associated with asthma episodes. The observation that the great majority of wheezing lower respiratory tract illnesses in early life are associated with acute viral infections suggests that viruses may also alter the development of the lungs or of the immune system, acting as co-factors for the inception of asthma. Whilst there is no doubt that viruses are important asthma exacerbation factors, the role of viral infections in the development of asthma still remains controversial.
Assuntos
Asma/virologia , Infecções Respiratórias/virologia , Asma/fisiopatologia , Citocinas/fisiologia , Humanos , Molécula 1 de Adesão Intercelular/fisiologia , Infecções por Picornaviridae/fisiopatologia , Sons Respiratórios , Infecções Respiratórias/fisiopatologia , RhinovirusRESUMO
Although tuberculosis is more common in transplant recipients than in the general population, most centres report that mycobacterial infection is very rare in comparison with the extreme variety of transplant-associated infections. Only 18 previous cases of tuberculosis-complicated lung or heart-lung transplants have been published. An unusual case is reported of Mycobacterium tuberculosis infection in a double-lung recipient who presented a radiographic feature of segmental pneumonia, mimicking a bacterial infection. Bronchoalveolar lavage revealed lymphocytosis (> 30% of isolated cells). Data regarding optimal treatment for tuberculosis in lung transplant recipients are limited. Nevertheless, therapy should not be different from that in other immunocompromised patients and should include an aggressive initial four-drug regimen (until the sputum cultures become negative) or a 6-month conventional therapy with two agents to which the organism is susceptible. Close follow-up is required to confirm the bacteriological response and minimize the likelihood of relapse. In this patient, treatment with a four-drug antituberculous regimen for 3 months followed by isoniazide and rifampicin for an additional 9 months was curative.
Assuntos
Transplante de Pulmão/efeitos adversos , Tuberculose Pulmonar/etiologia , Antituberculosos/uso terapêutico , Feminino , Humanos , Transplante de Pulmão/imunologia , Pessoa de Meia-Idade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologiaRESUMO
Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease due to the incomplete resolution of pulmonary emboli, leading to right heart failure, with a poor survival. Pulmonary endarterectomy (PEA) is the operation of choice for CTEPH. As there are no well-defined criteria to discriminate surgically accessible from inaccessible obstructive lesions, the operability assessment relies on the surgeon's experience. The recommended algorithms to perform a correct diagnosis of CTEPH still suggest the lung ventilation/perfusion scan, despite advances in computed tomography with 3-D reconstruction and magnetic resonance imaging. Selective pulmonary angiography is the gold standard to assess operability in CTEPH. Medical therapy should not be considered an alternative to PEA, as it should be reserved to patients with either peripheral disease, deemed inoperable by an experienced PEA surgeon, or persistent/recurrent pulmonary hypertension after PEA. Lung transplantation, when indicated, still represents a viable option for patients with either inoperable CTEPH or CTEPH with concomitant severe parenchymal lung disease that contraindicates PEA. The outcome of operable CTEPH is still best predicted after surgery. Remarkably, the recovery of exercise capacity is not as immediate as hemodynamic improvement, underlining the importance of early identification of surgical candidates before physical deconditioning.
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From a pathophysiologic perspective, the changes that occur in asthma are multiple, diverse, and complex. Assessment of the mechanical properties of the ventilatory apparatus provides several different types of information, depending on the gravity of the bronchial obstruction. During asthma, or induced bronchial obstruction, the function of the muscles is altered, causing changes in respiratory timing. Expiratory duration decreases more than inspiratory duration, and the functional residual capacity (FRC) increases, due to mechanical changes within the airways that lead to air trapping. The related hypoventilation is responsible for hypoxemia and hypercapnia, but it does not severely affect the diffusion capacity of the alveolocapillary membrane. We describe the pathophysiology of the bronchial obstruction in asthmatic patients, underlining the critical function of the respiratory muscles. Moreover, we clarify the relations between the ventilatory changes and gas-exchange alteration.
Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Asma/fisiopatologia , Brônquios/fisiopatologia , HumanosRESUMO
OBJECTIVE: The purpose of this study was to describe the CT findings of pneumonia in patients who had undergone lung transplantation and to determine if specific imaging features existed for the different infectious organisms. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of 262 patients with transplanted lungs at two lung transplantation centers. Patients with a documented pneumonia and correlating abnormal findings on CT (39 patients with 45 pneumonias) were included in the study. RESULTS. Of 45 pneumonias, Cytomegalovirus (n = 15), Pseudomonas (n = 7), and Aspergillus (n = 8) organisms were the most common single responsible infectious agents. The most common CT findings of pneumonia consisted of consolidation (n = 37; 82%), ground-glass opacification (n = 34; 76%), septal thickening (n = 33; 73%), pleural effusion (n = 33; 73%), and multiple (n = 25; 56%) or single (n = 2; 4%) nodules. No significant difference in the prevalence of findings was revealed among bacterial, viral, and fungal pneumonias (p >.05, chisquare test). Of 25 pneumonias in patients with a single transplanted lung, parenchymal abnormalities involved both lungs in 12 (48%), only the transplanted lung in 11 (44%), and only the native lung in two (8%). CONCLUSION: The manifestations revealed on CT of bacterial, viral, and fungal pneumonia after lung transplantation are similar, consisting of a combination of consolidation, ground-glass opacification, septal thickening, pleural effusion, or multiple nodules. Therefore, these findings cannot be used to suggest the infectious organisms in this patient population.
Assuntos
Transplante de Pulmão/efeitos adversos , Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/microbiologia , Pneumonia/virologia , Estudos RetrospectivosRESUMO
There are no reliable predictors of mortality in primary pulmonary hypertension (PPH). This study assessed whether exercise oxygen desaturation and distance achieved during a six-minute walk are associated with mortality in moderately symptomatic patients with PPH. Thirty-four patients with PPH underwent a pretreatment six-minute walk test, and an invasive haemodynamic assessment of pulmonary vasodilator reserve, to select the best treatment option (epoprostenol in 27 and nifedipine in 7). Median follow-up was 26 months (12 months for the nonsurvivors was 26%), and median survival, >46 months by Kaplan-Maier estimate. The mean+/-SD distance walked was 275+/-155 m and reduction in arterial oxygen saturation (Sa,O2) at maximal distance (deltaSa,O2) was 8.4+/-4.5%). A distance < or =300 m increased mortality risk by 2.4, and a deltaSa,O2 of > or = 10% increased mortality risk by 2.9. Only Sa,O2 at peak distance, deltaSa,O2 and pulmonary vascular resistance (PVR) were related to mortality. After adjusting for PVR, there remained a 27% increase in risk of death for each per cent decrease in Sa,O2. The six-minute walk distance and exercise oxygen saturation may be helpful in selecting patients with primary pulmonary hypertension for whom transplant listing is appropriate.
Assuntos
Teste de Esforço , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Oxigênio/sangue , Caminhada , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Epoprostenol/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Circulação Pulmonar , Taxa de Sobrevida , Resistência Vascular , Vasodilatadores/uso terapêuticoRESUMO
The alveolar macrophage (AM), a major defense cell in the lung, participates in immune and inflammatory reactions through the release of several regulatory and chemotactic cytokines. In particular, macrophages are considered to play a pivotal proinflammatory role in the production and maintenance of airway inflammation and bronchial hyperreactivity. To assess the phenotypic pattern of AM from asthmatic subjects, we performed the following experiments: 1) cytofluorometric analysis of specific phenotypic features (CD11b, CD14, CD16, CD45, HLA-DR, CD71, CD95, and CD44) 2) assessment of the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and the chemotactic regulatory cytokine IL-8 by unstimulated and lipopolysaccharide-stimulated AM. In these patients, we phenotypically characterized the AM, showing their strong proinflammatory activity also in patients with mild asthma. Their activity has been clarified by our biomolecular data that showed a constitutive basal IL-8 production by AM, and also indicated that IL-1 and TNF-alpha were able to upregulate the ability of activated human AM to produce IL-8 at the protein and messenger ribonucleic acid (mRNA) levels.