RESUMEN
T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.
Asunto(s)
Asma/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Hipersensibilidad Inmediata/inmunología , Interleucina-3/inmunología , Interleucina-5/inmunología , Mucosa Intestinal/inmunología , Enfermedades Pulmonares Obstructivas/inmunología , Adolescente , Adulto , Asma/tratamiento farmacológico , Asma/patología , Femenino , Humanos , Mucosa Intestinal/patología , Enfermedades Pulmonares Obstructivas/patología , Masculino , Mastocitos/ultraestructura , Persona de Mediana Edad , Estudios Prospectivos , Esteroides/uso terapéuticoRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of upper and lower motorneurons, leading to death in 3 to 5 years. Respiratory insufficiency and hypoxemia are closely linked during the clinical course of ALS. Chronic respiratory insufficiency and hypoxemia generally occur late in the disease course but rapid episodes of intermittent hypoxemia followed by reoxygenation can occur early and insidiously. Two pathways are involved in the response to hypoxemia: (i) hypoxia inducible factor-1 (HIF-1) and VEGF/HIF-2 and an erythropoietin (EPO) mediated pathway, in response to prolonged hypoxemia; and (ii) nuclear factor kappa-B (NFkappa-B) during acute hypoxemia followed by reoxygenation episodes, inducing inflammatory mediators: interleukin-6 (IL-6), TNF-alpha, cyclo oxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2). Our aim was to specify the role of the different functional pathways of response to hypoxemia in sporadic ALS patients, compared with neurological controls and according to the level of hypoxemia. We report the results of several studies of hypoxemic and/or inflammatory mediators in the cerebrospinal fluid (CSF) from ALS patients, according to their respiratory status, showing a selective defect of HIF-1 mediated angiogenic factors (VEGF and angiogenin [ANG]) during chronic hypoxia in sporadic ALS patients, compared to hypoxemic neurological controls; contrasting with an early activation of the NFkappa-B pathway since the isolated desaturation stage (IL-6, TNF-alpha, PGE-2, angiopoietin-2) in the same cohort of sporadic ALS patients. All these results are consistent with a selective impairment of the HIF-1 pathway during chronic hypoxemia in ALS patients. Inflammatory mediators were strongly elevated, since the early stage of the disease until chronic hypoxemia, suggesting a compensatory mechanism.
Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Hipoxia/fisiopatología , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/epidemiología , Biomarcadores , Hipoxia de la Célula/fisiología , Humanos , Hipoxia/epidemiología , Inflamación/metabolismo , Factores de RiesgoRESUMEN
BACKGROUND: Symptoms of allergic rhinitis (AR), particularly nasal congestion, can impair quality-of-life (QoL). However, only a modest correlation exists between these symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, suggesting that both be evaluated for a complete assessment of health. METHODS: Subjects with a > or =2-year history of moderate-to-severe AR to dust mite or cat dander were randomized to desloratadine 5 mg/day (n = 293) or placebo/day (n = 291) for 28 days. Primary endpoint was change from baseline in a.m./p.m. nasal congestion score. Secondary outcomes included change from baseline in total nasal symptom score, individual symptom scores and RQLQ scores (completed on days 1, 7, and 28). RESULTS: The Allergic Rhinitis and its Impact on Asthma criteria for persistent allergic rhinitis (PER) were fulfilled by 99% of subjects in the placebo arm. Between-treatment difference in a.m./p.m. nasal congestion score, observed from day 8 onward, significantly favored desloratadine (P = 0.0003). Desloratadine significantly improved a.m./p.m. nasal congestion and RQLQ scores after 1 week and at treatment end (P < 0.05). Improvements in 5 of 7 RQLQ domain scores exceeded the minimal important difference. On days 7 and 28, desloratadine was also significantly superior to placebo in mean change from baseline in a.m./p.m. total nasal symptom score and rhinorrhea score (both P < or = 0.01). Symptomatic benefit was primarily driven by improvement in nasal congestion and rhinorrhea. CONCLUSIONS: Desloratadine 5 mg/day significantly improved symptoms associated with PER, including nasal congestion, and provided significant improvement in QoL after 1 week of treatment.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1 no Sedantes , Loratadina/análogos & derivados , Obstrucción Nasal/tratamiento farmacológico , Calidad de Vida , Rinitis Alérgica Perenne/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Antagonistas de los Receptores Histamínicos H1 no Sedantes/uso terapéutico , Humanos , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Masculino , Persona de Mediana Edad , Rinitis Alérgica Perenne/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
Alveolar macrophages from nonatopic donors were passively sensitized with allergen-specific IgE antibody from the serum of asthmatic patients. A selective release of 4-8% of the lysosomal beta-glucuronidase of these cells occurred within 30 min of contact with the related allergen or with anti-human IgE antibody, in the absence of any mast or basophil cells. The cell reactivity was dependent on the interaction of macrophages with IgE, as shown by the disappearance of the allergen-induced enzyme release after heating or IgE-immune adsorption of the sensitizing serum, but not after IgG-adsorption. Alveolar macrophages from asthmatic patients behaved similarly to passively sensitized normal macrophages. Contact with the related allergen or with anti-IgE antibody induced the same percentage of enzyme release, demonstrating that these cells possess allergen-specific IgE bound on their surface. 18% of them formed rosettes with anti-IgE-coated sheep erythrocytes, and 15-22% with allergen-coated erythrocytes, but lost this property after preincubation with the specific allergen. The presence of IgE-specific receptors on the macrophage surface was demonstrated both at the ultrastructural level with immunoperoxidase labeling, and at low magnification by the formation of 15-18% rosettes with human IgE-coated erythrocytes. The formation of such rosettes was inhibited after incubation of alveolar phagocytes with aggregated myeloma IgE. On the basis of these observations, the participation of the alveolar macrophages in IgE-mediated pulmonary hypersensitivity must be considered. Its precise involvement requires, however, further investigations.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Asma/patología , Inmunoglobulina E/inmunología , Macrófagos/inmunología , Adulto , Alérgenos/inmunología , Basófilos/metabolismo , Femenino , Liberación de Histamina , Humanos , Macrófagos/enzimología , Masculino , Mastocitos/metabolismo , Microscopía Electrónica , Alveolos Pulmonares/citología , Receptores de Antígenos de Linfocitos B , Formación de RosetaRESUMEN
Animal studies have highlighted the potentially neuroprotective role of vascular endothelial growth factor (VEGF). Low levels of this growth factor have been found in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). VEGF (and other proteins, such as erythropoietin (EPO)) are produced in response to hypoxia via a common pathway involving a specific transcription factor (hypoxia-inducible factor, HIF) and a hypoxia responsive element (HRE) in the respective genes' promoter regions. In this study, we report finding the expected, high levels of VEGF and EPO in CSF from hypoxemic neurological controls, whereas EPO (but not VEGF) levels are high in the CSF from hypoxemic ALS patients. Hence, the VEGF levels in CSF from patients with ALS were significantly lower than those seen in hypoxemic controls. There was a trend towards higher CSF levels of EPO in hypoxemic ALS patients than in hypoxemic controls. Our results suggest that VEGF may not be produced in sufficient amounts in chronically hypoxic ALS patients and that this dysfunction may participate in the pathogenesis of the disease. The high EPO levels in hypoxemic ALS patients nevertheless suggest an intact common oxygen-sensor pathway.
Asunto(s)
Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Eritropoyetina/líquido cefalorraquídeo , Hipoxia/líquido cefalorraquídeo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/genética , Consumo de Oxígeno/fisiologíaRESUMEN
INTRODUCTION: We report a case of occupational hypersensitivity pneumonitis in a patient handling chicory leaves. CASE REPORT: The diagnosis was based symptoms of broncho-alveolitis with pyrexia, positive precipitins to moulds present on chicory, especially Fusarium, and the disappearance of the clinical and radiological manifestations following cessation of exposure to chicory. CONCLUSION: "Chicory worker's lung" is an occupational disease which should be considered in cases of respiratory symptoms suggestive of hypersensitivity pneumonitis and chronic exposure to chicory leaves.
Asunto(s)
Alveolitis Alérgica Extrínseca/etiología , Cichorium intybus/efectos adversos , Enfermedades Profesionales/etiología , Adulto , Femenino , Humanos , Hojas de la Planta/efectos adversosRESUMEN
INTRODUCTION: The manufacture of dental prostheses exposes the technician to inhalation of various potentially dangerous dusts (silica, hard metals, dental alloys and acrylic resins). BACKGROUND AND VIEWPOINT: Inhalation of dusts produced by the technician in the work place may lead to several respiratory disorders (pneumoconiosis, hypersensitivity pneumonitis, asthma, lung cancer). The continuous development of new materials leads to further manifestations of these disorders and justifies their notification, even in the absence of an accepted occupational disease. This step is taken inconsistently as many dental technicians are not salaried or insured. CONCLUSION: The seriousness of some of these disorders and the absence of effective treatment makes it important to develop effective methods of prevention for the protection of individuals and groups, and for early detection.
Asunto(s)
Prótesis Dental , Técnicos Dentales , Enfermedades Pulmonares/epidemiología , Enfermedades Profesionales/epidemiología , Tecnología Odontológica , Francia/epidemiología , Humanos , Enfermedades Pulmonares/economía , Enfermedades Pulmonares/prevención & control , Enfermedades Profesionales/economía , Enfermedades Profesionales/prevención & controlRESUMEN
INTRODUCTION: Update on the state of knowledge in the mild asthma (intermittent and persistent mild asthma, according to the GINA classification) literature, and position of a French Mild Asthma Working Group. STATE OF THE ART: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the epidemiology, physiopathology, clinical signs, and management of mild asthma. The present article shows the position of the working group on mild asthma descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation. Clinical signs and medicinal treatments will be presented in a second article. PERSPECTIVES: Between 50% and 75% of asthma patients, depending on the study, present mild asthma. Childhood-to-adulthood cohort monitoring found severity to be unchanged over developmental time. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Inflammation and airway-wall remodelling were always found, although of variable intensity, and non-specific (except for absence of infiltration by polymorphonuclear neutrophils). Corticosteroid therapy by inhalation reduces bronchial inflammation, but with little impact on airway-wall remodelling. CONCLUSION: The present findings should help clinicians in identifying and understanding mild asthma.
Asunto(s)
Asma/epidemiología , Corticoesteroides/uso terapéutico , Adulto , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/fisiopatología , Bronquios/efectos de los fármacos , Bronquios/patología , Bronquitis/patología , Bronquitis/fisiopatología , Niño , Estudios de Cohortes , Francia/epidemiología , Humanos , Neutrófilos/patologíaRESUMEN
OBJECTIVE: To update on the state of knowledge in mild asthma (intermittent and persistent mild asthma, according to the GINA classification) review the literature, and the position statement of the French Mild Asthma Working Group. METHODS: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the descriptive epidemiology, physiopathology, clinical signs, and management of mild asthma. The position of the working group on the descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation has been presented in a previous article. The present article focuses on the clinical features of mild asthma and the use of medication for it. RESULTS: Mild asthma was more frequent, more symptomatic, and less well controlled in children than in adults. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Patients with mild persistent asthma require controller medication every day: permanent low-dose inhaled corticosteroid monotherapy is the reference foundation treatment for persistent mild asthma. CONCLUSIONS: The present findings should help clinicians and guide them in their approach to managing this condition.
Asunto(s)
Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/epidemiología , Asma/fisiopatología , Bronquios/efectos de los fármacos , Bronquitis/diagnóstico , Bronquitis/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Quimioterapia Combinada , Francia/epidemiología , Humanos , Índice de Severidad de la EnfermedadRESUMEN
Mechanisms that allow a selective eosinophil emigration in different eosinophilic lung diseases remain poorly understood. In this study, we tested the hypothesis that eosinophils might participate in their own recruitment, particularly through adhesion molecule expression on human endothelial cells (EC). Blood eosinophils from donors with blood eosinophilia were purified and maintained in culture medium for 1 and 18 h. The expression of ICAM-1, E-selectin, and VCAM-1 on human umbilical vein endothelial cells (HUVEC) was evaluated by ELISA and flow cytometry analysis after addition of eosinophil supernatants. Eosinophil supernatants collected after 1 h induced a weak increase of CAM expression on HUVEC. In contrast, supernatants from eosinophils cultured for 18 h considerably amplified ICAM-1, E-selectin, and VCAM-1 expression on the surface of EC. These levels of CAM expression (in optical density determined by ELISA) were about two- or threefold more important than those obtained with eosinophil supernatants collected after a 1-h culture. The characterization of the implicated molecules showed that anti-IL-1beta antibodies significantly inhibited ICAM-1, E-selectin, and VCAM-1 expression, whereas anti-TNF-alpha antibodies only induced a moderate inhibition. Our data support the hypothesis that eosinophils, through the release of at least IL-1beta and TNF-alpha, might participate in the amplification of the inflammatory reaction by activating the vascular endothelium.
Asunto(s)
Selectina E/biosíntesis , Endotelio Vascular/inmunología , Eosinófilos/inmunología , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Membrana Celular/inmunología , Células Cultivadas , Citosol/inmunología , Endotelio Vascular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Interleucina-1/sangre , Interleucina-1/farmacología , Interleucina-6/sangre , Interleucina-6/farmacología , Interleucina-8/sangre , Interleucina-8/farmacología , Cinética , Proteínas Recombinantes/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Venas UmbilicalesRESUMEN
As an immunogen must contain both B- and T-cell epitopes, small peptides are usually reported as non-immunogenic unless coupled to a protein carrier. In this study, the immunogenicity of the Der p I synthetic uncoupled peptides (p52-71, p89-104, p117-133 and p176-187) previously reported as B-cell epitopes, was evaluated. Different schedules of immunization were used. Results indicated that by using the Vaitukaikis' method three injections of the same peptide without protein carrier was sufficient to induce an specific anti-peptide IgG antibody response (evaluated by ELISA). Indeed, the 16-20 amino-acid long peptides p52-71, p117-133 and p89-104 were revealed highly immunogenic in rabbits. Furthermore anti-peptide p52-71 and p117-133 antibodies were shown by Western-blotting or by neutralization assay to recognize the Der p I molecule either in denaturated or native form as well as Der f I (major allergen of Dermatophagoides farinae). Finally, taking into account the location of Der p I-derived peptides in the three-dimensional model of Der p I, the antigenicity and immunogenicity of peptides were discussed.
Asunto(s)
Alérgenos/inmunología , Glicoproteínas/administración & dosificación , Ácaros/inmunología , Péptidos/administración & dosificación , Secuencia de Aminoácidos , Animales , Formación de Anticuerpos , Antígenos Dermatofagoides , Linfocitos B/inmunología , Epítopos/inmunología , Glicoproteínas/química , Glicoproteínas/inmunología , Inmunización , Modelos Moleculares , Datos de Secuencia Molecular , Biosíntesis de Péptidos , Péptidos/química , Conejos , Ratas , Alineación de Secuencia , Linfocitos T/inmunologíaRESUMEN
INTRODUCTION: Immunoglobulin E (IgE) is a key factor of allergic reaction and is known to be involved in the immunopathology of asthma. In this review, we discuss the results of trials of a monoclonal antibody (omalizumab) against IgE in patients with allergic asthma. STATE OF THE ART: Omalizumab is a humanised murine IgG1 kappa monoclonal antibody which is administered subcutaneously every 2 to 4weeks at a dose calculated according to the patient's body weight and total plasma IgE concentrations. It binds free circulating IgE thus preventing it from binding to high affinity receptors. Omalizumab therapy significantly reduces asthma exacerbations, improves quality of life and has a steroid-sparing effect. It has a good safety profile. This treatment appears to be more effective in the patients with the most severe disease and the worst lung function. CONCLUSION AND PERSPECTIVES: Omalizumab therapy is an important novel treatment for difficult-to-control allergic asthma. Because of its systemic mechanism of action, it may be of particular use in patients displaying multiple allergic pathologies. It remains unknown whether the beneficial effects of omalizumab could be extended to patients with severe non allergic (so-called "intrinsic") asthma, a variant of the disease which is often difficult to control.
Asunto(s)
Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Asma/tratamiento farmacológico , Inmunoglobulina E/inmunología , Administración Oral , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Asma/sangre , Asma/diagnóstico , Asma/inmunología , Niño , Ensayos Clínicos Controlados como Asunto , Humanos , Inmunoglobulina E/sangre , Inyecciones Subcutáneas , Omalizumab , Placebos , Calidad de Vida , Pruebas Cutáneas , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
BACKGROUND: Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been shown to improve chronic refractory and fistulating Crohn's disease. Infliximab infusions have been associated both with immediate and delayed reactions. MATERIAL AND METHODS: Desensitisation was performed in four patients who had experienced immediate reactions to infliximab infusions and in one who had developed a delayed reaction. No therapeutic alternatives were available for these patients. Before desensitisation, skin tests were performed. RESULTS: Skin-tests were negative for all patients. Desensitisation was performed with serial dilutions of infliximab with monitoring of vital signs before each increment. After parenteral desensitisation, all five patients were able to tolerate infliximab infusion without complications or any requirement for antihistamines or steroids. However, two patients who had initially presented with an immediate reaction to infliximab experienced arthralgia and myalgia similar to a "serum sickness-type" of reaction 6 to 10 days after desensitisation. CONCLUSION: Even if there is no evidence of an allergic mechanism in infusion reactions to infliximab, successful desensitization can be achieved for patients experiencing acute reactions. The mechanism of desensitisation remains presently unknown. It is not yet possible to say if desensitization will be effective in preventing delayed reactions.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Desensibilización Inmunológica , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/terapia , Adulto , Anticuerpos Monoclonales/uso terapéutico , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfaRESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major health problem. Few data about COPD economic burden are available. METHODS: SCOPE was an observational economical retrospective and prospective study conducted in France in 2001, by 114 general practitioners (GPs) and 57 lung specialists. The aim was to describe the burden of COPD patients and to estimate the annual cost according to severity stages. Health resource utilization was collected by questionnaires over a 12-month period for 285 patients. RESULTS: It was a cost-of-illness analysis. COPD patients followed by a lung specialist were more severe than patients followed by a GP and had a higher level of medical resource consumption. The COPD disease and its complications explained 66% of the total cost. The main cost drivers were inpatient care (35%, or 1509,9 euros/year/patient) and prescription medications (31%, or 1340,6 euros/year/patient). The direct total cost varied according to COPD severity on account of inpatient care and respiratory assistance. DISCUSSION: This study confirmed the economic burden of COPD in France. Actions allowed to slow down the disease's evolution and to anticipate the exacerbation could reduce the cost.
Asunto(s)
Costos de la Atención en Salud , Enfermedad Pulmonar Obstructiva Crónica/economía , Anciano , Femenino , Francia , Humanos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Idiopathic chronic eosinophilic pneumonia (CEP) is a rare disorder of unknown cause with nonspecific respiratory and systemic symptoms but rather characteristic peripheral alveolar infiltrates on imaging, developing mainly in women and in atopic subjects. The disorder is highly responsive to oral corticosteroid therapy, but relapses are frequent on reducing or stopping treatment. The long-term course of the disease and data regarding outcome, particularly the need for prolonged oral corticosteroid therapy and the development of severe asthma, are somewhat contradictory. A multicentric retrospective study was conducted in an attempt to describe better the initial features and, above all, the later course of CEP in a large homogeneous series of 62 stringently selected patients of whom 46 were followed for more than 1 year. The prevalence of smokers was low (6.5%) and about half of our patients (51.6%) had a previous, and often prolonged, history of asthma. The clinical and roentgenographic features were in keeping with previous studies, but we found that computed tomography could disclose ground glass opacities not detected by X-ray, and that migratory infiltrates before treatment were more frequent (25.5%) than reported previously. The bronchoalveolar lavage cellular count always showed a striking eosinophilic pattern, thus allowing distinction between CEP and cryptogenic organizing pneumonia, both syndromes sharing many common clinical and imaging features. About two-thirds of the patients (68%) showed a ventilatory defect in pulmonary function tests, with about one-half of these presenting with an obstructive pattern, sometimes without previous asthma. Along with the submucosal eosinophilic infiltration noted in 2 patients without ventilatory defect, this is strong evidence to confirm that CEP is not only an alveolointerstitial but also an airway disease. The dramatic response to oral corticosteroid therapy was observed in all treated patients. Although only 1 patient initially treated for less than 6 months did not relapse, longer oral corticosteroid therapy in no way provided protection from further relapses. We thus propose to try to wean oral corticosteroid therapy after 6 months in patients without severe asthma, because recurrences remain responsive to oral steroids. However, prolonged oral corticosteroid therapy was necessary in the majority of patients, with 68.9% of those followed for more than 1 year still on oral corticosteroid therapy at the last follow-up, either because of relapse or because of severe asthma.
Asunto(s)
Eosinofilia Pulmonar , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Eosinofilia Pulmonar/complicaciones , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/patología , Eosinofilia Pulmonar/terapia , Recurrencia , Estudios RetrospectivosRESUMEN
Although respiratory involvement occurs in 50% of patients with relapsing polychondritis (RP) and augurs a poor prognosis, few previous studies have provided complete descriptions of respiratory tract involvement. For this reason, we investigated the respective role of clinical, functional, endoscopic, and radiographic (computed tomography [CT]) examinations in 9 consecutive patients with RP and lower respiratory tract localization. All exhibited cough, dyspnea, and wheezing. Eight had a nonreversible obstructive pattern with a marked decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman functional criteria were evaluated to differentiate upper from lower respiratory tract involvement; they were consistent with the results of other examinations in 4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9 patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in 4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in 8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients. Tracheobronchial wall thickening and/or calcifications were observed in 7 cases. Clinical symptoms are of poor specificity for defining respiratory involvement precisely, although degree of dyspnea is correlated to the decrease in forced expiratory volume in 1 second (FEV1). Functional criteria were helpful in evaluating the obstructive ventilatory defect but did not differentiate, in most cases, the respective part of lower and upper respiratory involvement when using Rotman criteria. Compared to CT findings, endoscopic examination failed to identify tracheal and bronchial stenosis and tracheal wall alterations at an early stage of the disease. In our series CT appears to be a reliable method to identify tracheal and bronchial involvement and can be repeated safely during the course of the disease.
Asunto(s)
Bronquiectasia/etiología , Disnea/etiología , Policondritis Recurrente/complicaciones , Policondritis Recurrente/diagnóstico , Atelectasia Pulmonar/etiología , Estenosis Traqueal/etiología , Adulto , Anciano , Bronquiectasia/diagnóstico , Broncoscopía/métodos , Disnea/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atelectasia Pulmonar/diagnóstico , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Estenosis Traqueal/diagnósticoRESUMEN
Since the first report in 1983, blood platelet reactivity from patients with immediate hypersensitivity reactions, and particularly allergic asthma and aspirin-sensitive asthma, has been evaluated by the release of cytotoxic mediators able to induce the death of parasite larvae, and by the generation of oxygen derived free radicals, measurable by chemiluminescence. We demonstrate here that platelets are able to reduce MTT tetrazolium salt proportionally to the stimulation level in two models of platelet triggering, one IgE-dependent and one aspirin-dependent. This method correlated significantly with the cytotoxicity assay of platelet stimulation (r = 0.965, p < 10(-5) for IgE-dependent stimulation; r = 0.723, p < 10(-4) for aspirin-dependent stimulation). The MTT colorimetric assay should complement or possibly replace previous methods of assessing platelet activation which were of limited use allowing broader investigations on the involvement of platelets in immune processes and in allergic or pseudoallergic reactions.
Asunto(s)
Plaquetas/inmunología , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo , Aspirina/farmacología , Colorimetría , Citotoxicidad Inmunológica , Humanos , Inmunoglobulina E/inmunología , Oxidación-ReducciónRESUMEN
The demonstration of a specific receptor for IgE on non-mast cell or basophil leucocytes, such as mononuclear phagocytes, eosinophils and platelets, suggests that these cells may participate directly in immunological disorders of allergy. In this study, inhibition by nedocromil sodium of IgE-dependent activation of human alveolar macrophages, blood monocytes and platelets was investigated. Nedocromil sodium produced an inhibition of IgE-mediated generation of cytotoxic molecules from monocytes and platelets together with a concomitant inhibition of their oxidative metabolism, measured by chemiluminescence. In addition, nedocromil sodium reduced the ability of alveolar macrophages to synthesise and release mediators, estimated by beta-glucuronidase activity. Furthermore, nedocromil sodium inhibited the abnormal response to aspirin of platelets from aspirin-sensitive asthmatics at therapeutic concentrations. These studies confirm that nedocromil sodium acts on a cell compartment other than the classical mast cell population in IgE-dependent allergy and asthma.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Asma/inmunología , Plaquetas/efectos de los fármacos , Inmunoglobulina E/inmunología , Activación de Macrófagos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Quinolonas/farmacología , Animales , Aspirina/farmacología , Asma/fisiopatología , Supervivencia Celular/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Glucuronidasa/metabolismo , Humanos , Técnicas In Vitro , Mediciones Luminiscentes , Lisosomas/enzimología , Lisosomas/metabolismo , Nedocromil , Schistosoma mansoni/inmunología , EsquistosomicidasRESUMEN
Follow-up of patients with subclinical inflammatory alveolitis associated with systemic diseases may represent the best opportunity to study the mechanisms responsible for the development of interstitial lung disease. We report a seven-year sequential pulmonary evaluation of one patient with clinically isolated gastric sarcoidosis, treated by gastrectomy, without evidence of clinical, radiologic or functional lung impairment and with chronic subclinical lymphocyte alveolitis. Five years later, she developed an overt interstitial lung disease characterized by fine crackles, diffuse parenchymal opacities and impaired diffusing capacity, preceded by an expansion of polymorphonuclear neutrophils in the lower respiratory tract, raising the hypothesis that these cells may be implicated in the pathogenesis of pulmonary derangement in sarcoidosis. This observation illustrates the importance of pulmonary follow-up of unaffected patients with systemic diseases and with subclinical inflammatory alveolitis, and the potential predictive value of neutrophil alveolitis in the pulmonary outcome of these patients.
Asunto(s)
Enfermedades Pulmonares/etiología , Sarcoidosis/complicaciones , Gastropatías/complicaciones , Adulto , Femenino , Estudios de Seguimiento , Humanos , Pulmón/patología , Enfermedades Pulmonares/patología , Sarcoidosis/patología , Factores de TiempoRESUMEN
Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.