RESUMEN
BACKGROUND: Allergic rhinitis is associated with significant impairment in quality of life and therefore has a significant impact on the indirect health care costs associated with treatment of chronic rhinitis in the United States. It has been stated that early intervention in the treatment of chronic rhinitis by an allergy specialist improves health outcomes but few unbiased studies have been conducted to substantiate this claim. OBJECTIVE: This study measured quality of life outcomes in the treatment of chronic rhinitis by an allergy specialist. METHODS: Quality of life changes were assessed using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short-Form" 36-item questionnaire (SF-36) in patients before and after treatment of chronic rhinitis symptoms by a board-certified allergist. Patients with chronic rhinitis were asked by a 3rd year medical student to complete these questionnaires prior to any contact with the allergist. Treatment by the allergist included counseling on avoidance measures when appropriate and a new medication regimen. Patients were contacted by the 3rd year medical student 3 to 5 months later to complete follow-up RQLQ and SF-36 surveys. All data analysis was conducted independently by the 3rd year medical student. RESULTS: Complete sets of pre-treatment and post-treatment surveys were obtained from 19 patients. Perennial allergic rhinitis was diagnosed for 13 patients, perennial allergic rhinitis with a seasonal component was diagnosed for three patients, vasomotor rhinitis was diagnosed for two patients and mixed allergic and non-allergic rhinitis was diagnosed for one patient. Statistically significant improvement was observed in four of the nine health concepts measured by the SF-36 questionnaire. Significant changes above the minimal important difference (MID) were observed post-treatment in six of eight RQLQ dimensions. CONCLUSIONS: This study indicates that intervention by a board-certified allergist significantly improves many areas of health-related quality of life. Further studies comparing health care outcomes and costs of treating chronic rhinitis by primary care physicians to early intervention by allergy specialists are warranted.
Asunto(s)
Calidad de Vida , Rinitis/terapia , Adulto , Alergia e Inmunología , Enfermedad Crónica , Femenino , Humanos , Masculino , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/terapia , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/terapia , Rinitis Vasomotora/diagnóstico , Rinitis Vasomotora/terapia , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Optimal signal transduction through the T cell receptor (TCR)/CD3 complex requires the coordinated activities of protein tyrosine kinases (PTKs) Fyn and Lck in addition to protein tyrosine phosphatases (PTPases) such as CD45. Although T cells stimulated with anti-CD3 monoclonal antibodies (mAb) exhibit age-related reductions in tyrosine phosphorylations of cellular proteins, it is unknown if the reduction represent abnormalities in PTKs or PTPases. In the current studies, immune complex kinase assays showed that the stimulation of peripheral blood T (PBT) cells from young humans with cross-linked anti-CD3 epsilon mAb OKT3 induced increased Fyn catalytic activity while anti-CD3 stimulation failed to induce significant increases in Lck activation. By contrast, Fyn activation in anti-CD3 stimulated PBT cells from a substantial proportion of elderly humans was reduced compared to anti-CD3 stimulated PBT cells from young humans. Also, we failed to find any increase in anti-CD3 stimulation of Lck activity in PBT cells from elderly subjects that could compensate for the decline in Fyn activity. However, no age-related alterations were detected in PBT cell expression of Fyn or Lck that might contribute to the changes in enzymatic activity. The results of other experiments demonstrated that the functional activities of PTPases in PBT cells from elderly subjects were equivalent to PBT cells from young subjects. These observations suggest that aberrant regulation of TCR/CD3 coupled PTKs may contribute to the age-related defects in signaling cascades and immune responsiveness of human T cells.
Asunto(s)
Envejecimiento/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Complejo Receptor-CD3 del Antígeno de Linfocito T/metabolismo , Linfocitos T/metabolismo , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Anticuerpos Monoclonales/metabolismo , Catálisis , Células Cultivadas , Activación Enzimática , Femenino , Humanos , Antígenos Comunes de Leucocito/metabolismo , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito , Masculino , Datos de Secuencia Molecular , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-fyn , Linfocitos T/citologíaRESUMEN
Age-related changes in the functional properties of human T cells are well described, but less is known about possible changes in T cell signaling pathways. The signaling pathways mediated by mitogen-activated protein kinases (MAPK) are considered essential for normal cellular growth and function. Several stimuli trigger MAPK activation in human T cells and MEK (MAPK or ERK kinases) are immediate upstream inducers of MAPK activation. The current study investigated if aging might influence the activation and expression of MAPK and MEK in human T cells. Exposure of peripheral blood T cells from young subjects to PHA or cross-linked anti-CD3 monoclonal antibodies stimulated rapid increases in MAPK and MEK enzymatic activity. By contrast, significant reductions of MAPK and MEK activation were observed in stimulated T cells from 7 of 13 elderly subjects. Kinetic studies showed that the age-related impairments represented reduction in both the levels and duration of MAPK activation. In addition, Western immunoblot analysis did not reveal significant age-related differences in T cell expression of p42mapk/ERK2, p44mapk/ERK1, or MEK, suggesting impairments in upstream inducers of MEK/MAPK activation. Other experiments determined if agents that directly stimulate upstream Ras or Raf kinase components of the early MAPK cascade might reverse the age-related impairments of MAPK activation. Treatment of elderly T cells with fluoroaluminate (AlF(-)4), phorbol esters/Ca2+ ionophores, or okadaic acid stimulated increased MAPK activation compared to anti-CD3. However, these agents failed to restore MAPK activation in elderly T cells to the levels seen in young T cells. These results suggest that aberrancies in the MAPK activation cascade may underlie the age-related reductions of MAPK activation in human T cells stimulated via the TCR/CD3 complex.