What are the best estimates of pediatric asthma control?

PURPOSE OF REVIEW: To evaluate asthma outcome measures in the face of the variable nature of asthma. The outcome measures are divided into objective and subjective clinical measures, humanistic measures such as quality of life, and costs of asthma control. RECENT FINDINGS: Objective measures of asthma include those traditionally used such as spirometry, peak expiratory flow rate, and airway hyperresponsiveness. Recently, more attention has been geared towards markers of inflammation including exhaled nitric oxide and sputum eosinophils. Subjective measures of asthma control include patient-derived parameters such as number of wheezing episodes, nocturnal symptoms, exercise-induced symptoms, short-acting beta-agonist use, steroid bursts, emergency-department visits, and hospitalizations. Asthma-related quality of life is related to asthma morbidity, and patients with better baseline quality of life have improved outcomes. Asthma-related costs include direct costs mostly comprised of hospitalizations and emergency-room visits, and indirect costs including school absenteeism. SUMMARY: There is no ideal outcome measure for evaluating pediatric asthma control, but each of these outcome measures must be used together to evaluate a patient at each outpatient visit. Patient-centered measures of asthma control must also be further incorporated into office visits for improved asthma management.

Research upregulation of CD23 (FcepsilonRII) expression in human airway smooth muscle cells (huASMC) in response to IL-4, GM-CSF, and IL-4/GM-CSF.

BACKGROUND: Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. METHODS: Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. RESULTS: The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 +/- 4.2% (IL-4), 15.6 +/- 2.7% (GM-CSF) and 32.9 +/- 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Ralpha and a low level expression of IL-2Rgammac in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rgammac. CONCLUSION: CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC.