Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma.

Allergic asthma is a chronic respiratory disease that results from an exaggerated inflammatory response in the airways. Environment stimuli, such as pollen and HDM, cause activation and migration of inflammatory WBCs into the respiratory tract, where they cause lung damage. Migration of these WBCs is dependent on the active configuration of the ß2 integrin LFA-1. The experimental therapeutic agent LtxA specifically targets active LFA-1 and causes cell death. We investigated the association between LFA-1 and allergic asthma and hypothesized that targeting LFA-1 with LtxA could be an attractive strategy for treatment of the condition. We examined LFA-1 (CD11a) levels on PBMCs from patients with allergic asthma compared with healthy controls. Patients exhibited a significantly higher percentage of PBMCs expressing LFA-1 than healthy controls. Furthermore, the level of LFA-1 expression on patient PBMCs was greater than on healthy PBMCs. We identified a unique cellular population in patients that consisted of CD4(-) CD11a(hi) cells. We also evaluated LtxA in a HDM extract-induced mouse model for allergic asthma. LtxA caused resolution of disease in mice, as demonstrated by a decrease in BALF WBCs, a reduction in pulmonary inflammation and tissue remodeling, and a decrease in proinflammatory cytokines IL-4, IL-5, IL-9, IL-17F, and IL-23α in lung tissue. LFA-1 may serve as an important marker in allergic asthma, and the elimination of activated WBCs by use of LtxA could be a viable therapeutic strategy for treating patients with this condition.

The impact of adenotonsillectomy on asthma in children.

OBJECTIVE: To investigate the impact of adenotonsillectomy on asthma in the pediatric population. STUDY DESIGN: Retrospective chart review. METHODS: All children who underwent adenotonsillectomy at our institution from 2002-2007 were identified from a medical records database. Of the 560 charts reviewed, 93 of the patients had the diagnosis of asthma from a pediatric pulmonologist. Outcome measures of asthma control were analyzed one year preoperatively and one year postoperatively and included: hospital visits, systemic steroid use, asthma medication use, and asthma control test scores. RESULTS: There was a statistically significant improvement in postoperative asthma severity in all measures including mean hospital visits, systemic steroid administration, asthma medication use, and childhood asthma control test scores (p<0.01). CONCLUSION: This study suggests that adenotonsillectomy, which provides improvement in the upper airway of children, may in turn lead to improvement of the lower airways of children, especially those with bronchial asthma.