RESUMEN
The aims of management in mild-to-moderate stable chronic obstructive pulmonary disease (COPD) are to improve symptoms and quality of life (QOL), reduce decline in lung function, prevent and treat complications, increase survival while maintaining QOL, and minimize the adverse effects of treatment. Bronchodilator therapy is the keystone of improving COPD symptoms and functional capacity. The primary objective of this open-label study was to compare the efficacy and tolerability of salmeterol 50 microg BID administered by metered-dose inhaler versus oral, titrated, sustained-release theophylline BID, both given for 3 months to patients with a clinical history of chronic bronchitis. The secondary objectives of the study were to evaluate the safety profile of the two drugs for an additional 9-month period and to assess changes in QOL both within and between treatment groups, using the 36-Item Short Form (SF-36) Health Survey. One hundred seventy-eight outpatients (122 men, 56 women; mean age, 56 +/- 12.9 years; mean body weight, 76.1 +/- 11.8 kg) were randomized to the two treatment groups. Patients receiving salmeterol showed significant improvement in mean morning peak expiratory flow rate (16.56 L/min) over the 3-month period compared with patients receiving theophylline (P = 0.02). Salmeterol also significantly increased the percentage of symptom-free days and nights with no additional salbutamol requirement (P < 0.01). A significant difference was found between increases in forced expiratory volume in 1 second compared with baseline for salmeterol compared with theophylline throughout the initial 3-month period (0.13, 0.16, and 0.16 L at months 1, 2, and 3, respectively) and during the additional 9 months. The incidence of adverse events was similar in the two groups (salmeterol, 49.5%; theophylline, 49.4%), with a lower percentage of pharmacologically predictable adverse events in patients receiving salmeterol (4%) compared with those receiving theophylline (14.8%). Both drugs improved QOL, as measured by effects on the eight aspects of life experience analyzed by the SF-36 questionnaire. Salmeterol therapy was effective in more aspects, and the improvements seen in each were numerically greater than those seen with theophylline therapy. Statistically different changes between the two treatment groups were reported for physical functioning, changes in health perception, and social functioning (P = 0.02, P = 0.03, and P = 0.004, respectively). These data suggest that inhaled salmeterol 50 microg BID was more effective and better tolerated than oral, titrated theophylline and allowed better long-term control of airways obstruction and symptoms with improved lung function in patients with COPD.
Asunto(s)
Albuterol/análogos & derivados , Broncodilatadores/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Enfermedades Pulmonares Obstructivas/psicología , Calidad de Vida , Teofilina/uso terapéutico , Adulto , Anciano , Albuterol/administración & dosificación , Albuterol/efectos adversos , Albuterol/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Femenino , Humanos , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Pruebas de Función Respiratoria , Xinafoato de Salmeterol , Teofilina/administración & dosificación , Teofilina/efectos adversosRESUMEN
In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.
Asunto(s)
Anciano de 80 o más Años , Envejecimiento/inmunología , Autoanticuerpos/sangre , Adulto , Anciano , Antígenos Nucleares , Autoanticuerpos/inmunología , Cardiolipinas/inmunología , ADN/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/inmunología , Tiroglobulina/inmunologíaRESUMEN
We describe an HLA-B8, DR3-positive patient with localized morphea after silicone gel breast implantation for cosmetic reasons. We believe that this case suggests that a genetic background, i.e. HLA-B8, DR3 haplotype, is involved in the autoimmune response to silicone.
Asunto(s)
Implantes de Mama/efectos adversos , Antígeno HLA-B8/inmunología , Antígeno HLA-DR3/inmunología , Esclerodermia Localizada/inducido químicamente , Siliconas/efectos adversos , Cirugía Plástica , Adulto , Relación CD4-CD8 , Femenino , Glucocorticoides/uso terapéutico , Antígeno HLA-B8/genética , Antígeno HLA-DR3/genética , Humanos , Mamoplastia , Prednisona/uso terapéutico , Esclerodermia Localizada/tratamiento farmacológico , Esclerodermia Localizada/inmunologíaRESUMEN
BACKGROUND: Initial attempts to evaluate the association between allergic rhinitis and non-specific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophils. OBJECTIVES: The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchial hyperreactivity, in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils. METHODS: Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skin-prick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen, 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine), total serum IgE and blood eosinophil counts were measured during and out of the pollen season. RESULTS: During pollen season, 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled methacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 15 out of 16 patients were Parietaria-sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria-sensitive rhinitis bronchial responsiveness significantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts. CONCLUSIONS: Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non-specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE, eosinophil and bronchial hyperresponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.
Asunto(s)
Hiperreactividad Bronquial/fisiopatología , Eosinófilos , Inmunoglobulina E/sangre , Polen/inmunología , Rinitis Alérgica Estacional/fisiopatología , Estaciones del Año , Adulto , Asma/fisiopatología , Hiperreactividad Bronquial/inmunología , Femenino , Humanos , Masculino , Cloruro de Metacolina , Pruebas de Función Respiratoria , Rinitis Alérgica Estacional/inmunología , Sicilia , Pruebas Cutáneas , Estadísticas no ParamétricasRESUMEN
BACKGROUND: In allergic rhinitis, mast cells, activated by cross-linking of allergen to mast cell-bound specific IgE, release both vasoactive mediators related to the early nasal symptoms and chemotactic mediators that attract inflammatory cells, such as eosinophils, related to the late-phase response. OBJECTIVE: We have analyzed, during and out of pollen season, in blood and nasal fluid from patients allergic to grass pollen, histamine and tryptase to monitor the early phase markers and eosinophil and eosinophil cationic protein (ECP) to monitor the late phase. METHODS: Twenty patients were enrolled in the study. As a control, we studied 10 nonatopic subjects. Mediators and eosinophils were assessed in blood and nasal fluid. Histamine was tested only in nasal fluid. RESULTS: During pollen season, tryptase but not histamine increased in nasal fluids from patients (2.96 vs 0.22 U/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.63, p = 0.003). Tryptase was not detected in serum. Eosinophils increased in nasal cytology (17.0% vs 2.0%, p = 0.001) and in the blood (265 vs 12.7 x 10(6) L, p = 0.001) from patients, but they did not correlate with symptom scores. ECP increased only in the nasal lavage (1633 vs 1.30 ng/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.53, p = 0.016). CONCLUSIONS: Both ECP and tryptase increase in nasal secretion in natural disease. Therefore the measurement of tryptase and ECP levels in nasal fluid might be a useful clinical test for monitoring disease activity and the effects of therapeutic agents.
Asunto(s)
Eosinófilos/química , Mediadores de Inflamación/análisis , Mediadores de Inflamación/sangre , Mastocitos/química , Líquido del Lavado Nasal , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Adulto , Eosinófilos/efectos de los fármacos , Femenino , Humanos , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/metabolismo , Mediadores de Inflamación/farmacología , Recuento de Leucocitos , Masculino , Mastocitos/efectos de los fármacos , Poaceae/inmunología , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/metabolismo , Estaciones del AñoRESUMEN
A large number of T cell dysfunctions have been observed in the elderly. The most widely observed is the inability of these cells to proliferate at a level comparable to T cells from young individuals after stimulation by mitogens. To better characterize T cell impairment, we have focused on the in vitro T cell activation, analyzing by flow cytometry the activation molecules CD69 and CD71 on mitogen-stimulated lymphocytes from young and elderly subjects. The results show that the percentages of CD69+ and CD71 + T cells were significantly decreased in cultures from elderly subjects when compared to values obtained culturing cells from young individuals. The differences observed seem not due to differences in CD4 and CD8 rates in the "old' cells that underwent activation, since, following activation, the pattern of CD4 and CD8 phenotypes was the same in both groups of subjects. Signals from CD69 are relevant in controlling cytokine gene expression because its stimulation leads to interleukin-2 production and increases its receptor expression. The interaction of this cytokine with its cellular receptor is an essential requirement for T lymphocytes to express CD71 and to start proliferation. Thus, a key role in the age-associated impairment of T cell activation could be played by an ineffective modulation of CD69 expression suggesting a defect in the signal transduction pathway of the T cell receptor-CD3 complex in elderly.
Asunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación de Linfocitos B/sangre , Antígenos de Diferenciación de Linfocitos T/sangre , Activación de Linfocitos , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Femenino , Humanos , Lectinas Tipo C , Masculino , Receptores de TransferrinaRESUMEN
The aim of the present study was to compare, during the pollen season, serum levels of total IgE and soluble CD23 (sCD23) from patients with allergic bronchial asthma, with those from healthy subjects. Significantly higher levels of total IgE and sCD23 were found in patients with asthma compared to the control group. Both in normal controls and in asthmatic patients, a significant correlation was shown between the levels of these two molecules. In asthmatic patients, significant correlations were found for both total IgE and sCD23, with lung function measured as bronchial responsiveness to inhaled methacholine. These results suggest that in asthmatic patients, in addition to the study of total serum IgE levels, the assessment of sCD23 serum levels may be helpful in the evaluation of disease activity.
RESUMEN
We have analysed the relationship of blood eosinophil count and serum eosinophil cationic protein (ECP) levels in patients with acute and chronic idiopathic urticaria. The ECP levels and eosinophil counts were measured in the peripheral blood of 15 patients with acute urticaria, 25 with chronic idiopathic urticaria and 10 normal healthy subjects. Blood eosinophil counts and serum ECP levels increased in all patients with acute urticaria. Concerning patients affected by chronic urticaria, taking into account the recrudescence of the disease at the moment of taking the blood sample, only symptomatic patients showed increased eosinophil blood values whereas serum ECP levels were increased both in symptomatic and asymptomatic patients. Furthermore, serum ECP levels in chronic urticaria did not correlate with the peripheral eosinophil counts, as they did in acute urticaria. The results of the present study indicate that eosinophils may play a role in the inflammatory mechanisms in patients with acute and chronic urticaria showing a positive correlation between serum ECP levels and disease activity.
RESUMEN
BACKGROUND: In atopic asthma there is strong evidence of eosinophils playing an active role in pathogenesis. Some investigations demonstrated that eosinophil cationic protein (ECP) serum levels increased in atopic patients with asthma during pollen season. OBJECTIVE: The aim of the study was to evaluate the effects of short-term (1 week) beta 2-agonist treatment on lung function and eosinophil activity in asthmatic patients. METHODS: We used an open, randomized, cross-over design to compare the effects of salbutamol (200 micrograms q.i.d.) and salmeterol (50 micrograms b.i.d.) on peak expiratory flow rate (PEFR), blood eosinophil count and serum levels of ECP as a measure of eosinophil activity in 20 mild atopic asthmatics. RESULTS: Morning and evening PEFR values were both significantly higher during salmeterol treatment than during the salbutamol period. Conversely, both morning and evening daily asthma symptom scores were significantly lower during salmeterol treatment compared with those recorded during the salbutamol period. The mean basal eosinophil blood count on salmeterol treatment (601 +/- 189 mm3) was not higher than the mean count on salbutamol treatment (612 +/- 204 mm3). After both treatments the mean eosinophil blood counts were unchanged (619 +/- 189 mm3 and 576 +/- 212 mm3, respectively). No significant differences in blood eosinophil counts were observed between or within treatments at any time. No significant difference was observed in baseline mean ECP serum concentration (43.8 +/- 26.3 micrograms/L on salmeterol treatment and 41.7 +/- 29.8 micrograms/L on salbutamol treatment, respectively). After salmeterol treatment the mean ECP serum concentration had fallen significantly to 20.9 +/- 18.6 micrograms/L (P < 0.01), whereas after salbutamol treatment it was unchanged (42.0 +/- 25.1 micrograms/L). Salmeterol treatment produced a decrease in ECP serum levels without any changes in blood eosinophil count. CONCLUSION: This study demonstrates that salmeterol affords a significant improvement in asthma control during the pollen season, measured by both subjective and objective parameters, compared with salbutamol. This greater efficacy may be related to inhibition of eosinophil degranulation during the pollen season.
Asunto(s)
Albuterol/análogos & derivados , Albuterol/farmacología , Asma/tratamiento farmacológico , Proteínas Sanguíneas/efectos de los fármacos , Polen/inmunología , Ribonucleasas , Adulto , Asma/sangre , Asma/fisiopatología , Proteínas Sanguíneas/metabolismo , Recuento de Células , Estudios Cruzados , Proteínas en los Gránulos del Eosinófilo , Eosinófilos/efectos de los fármacos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/tratamiento farmacológico , Hipersensibilidad Inmediata/fisiopatología , Recuento de Leucocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio/efectos de los fármacos , Polen/citología , Rinitis Alérgica Estacional/etiología , Rinitis Alérgica Estacional/fisiopatología , Xinafoato de SalmeterolRESUMEN
The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation of the immune system, in patients with allergic bronchial asthma, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD4 were found in patients with asthma compared with the control group. In contrast, lower levels of soluble CD8 values were found in patients with asthma compared to the control group. Significant correlations were found for both sIL-2R and sCD4 and these two molecules, with lung function measured as bronchial responsiveness to inhaled methacholine. These results strengthen previous suggestions that in allergic bronchial asthma, activation of T cells plays a significant role in the disease pathogenesis.
RESUMEN
During pregnancy, the ideal would be to abstain from the use of any drug, at least during the first three months. In fact, none of the drugs currently used for the therapy of allergies has been classified by the FDA and European Commission on the basis of controlled human and animal studies as completely negative from the point of view of untoward effects in pregnancy. The following are considered comparatively safe: disodium cromoglycate, diphenhydramine, chlorpheniramine, hydroxyzine, mebhydroline, brompheniramine, inhaled beta 2-agonists, xanthine bronchodilators, pseudoephedrine, and topical nasal treatment with beclomethasone dipropionate in the last trimenon. On the contrary, specific immunotherapy is inadvisable. In the case of anaphylaxis, epinephrine and ephedrine are drugs of choice, while in asthma monitoring of PEFR is essential for appropriate management. For rhinitis, DSCG and beclomethasone diproprionate appear to he comparatively safe. For urticaria, hydroxyzine or possibly ephedrine should be preferred. In case of a history of untoward drug effects, oral antibiotics should be preferred (erythromycin or micamycin); for atopic dermatitis the preference is for topical treatment with hydrocortisone.
Asunto(s)
Hipersensibilidad/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Anafilaxia/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Embarazo , Hipersensibilidad Respiratoria/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológicoRESUMEN
It is well known that ageing is associated with various alterations of the lymphoid cell functions. Although both B and T cell are affected, the last appear to be more sensitive to ageing process. During the past years, to gain insight into thé mechanism(s) of this impairment, effort has been centered on the helper T cells specifically engaged in the production of interleukin-2 (IL-2) because of the pivotal role played by this cytokine in the activation of several immune functions. The results have demonstrated that the ability to produce IL-2 declines with age. In this paper we report the results of a study performed to determine the influence of age on the capacity to produce gamma-interferon (gamma-IFN), interleukin-4 (IL-4) and interleukin-6 (IL-6). Mononuclear cells from young and old subjects were assessed for cytokine producing capacity in response to phytohaemagglutinin stimulation. A significant decrease of gamma-IFN production by old subjects has been observed. No significant difference was instead observed between the old subjects and the young ones as regards IL-4 and IL-6 production. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in elderly, i.e. a normal or increased humoral response in face of a low T cell immune responsiveness.