Effects of omalizumab in patients with food allergy.

Omalizumab is a novel therapy approved for treating patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. We examined the efficacy of omalizumab as a treatment for IgE-mediated food allergy. An Institutional Review Board-approved prospective pilot study was performed to assess the efficacy of omalizumab in 22 patients with persistent asthma and concomitant IgE-mediated food allergy. All patients showed skin test positivity to foods and experienced allergic food reactions based on history. Patients were interviewed on unintentional and/or unauthorized exposures to sensitized foods. Thirteen female and nine male patients (range, 4-66 years old; mean, 38 years) were evaluated in a private practice setting. Mean IgE level was 1120.74 IU/mL. Sensitized allergens included fish, shellfish, peanuts, tree nuts, egg, soybean, and wheat. All 22 (100%) patients maintained significant improvement as shown by a decrease/lack of clinical symptoms on reexposure to sensitized foods. Clinical improvement by the sixth dosage of omalizumab (150-300 mg q. 2-4 weeks) was noted by history and physical examination. Eight patients noted a decrease in their food-induced atopic dermatitis, 13 patients noted a decrease in their food-induced asthma symptoms, 3 patients noted a decrease in their food-induced urticaria, 6 patients noted a decrease in their food-induced rhinosinusitis symptoms, and 9 patients showed efficacy for angioedema and/or anaphylaxis. While treating asthma patients with omalizumab, patients subjectively observed a reduction in their concomitant IgE-mediated food allergy symptoms.

Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study.

Omalizumab is a unique biologic therapeutic drug approved for treating atopic patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. This study was performed to examine the efficacy of omalizumab for the treatment of atopic dermatitis (AD), a disease with significant morbidity. A prospective analysis was performed to assess the efficacy of omalizumab in 21 patients with moderate to severe persistent allergic asthma and AD. Patients were stratified into the following groups: very high IgE (>700 IU/mL), high IgE (186-700 IU/mL), and normal IgE (0-185 IU/mL). AD severity was assessed at 0, 1, 3, 6, and 9 months via an Investigator Global Assessment index. Twenty-one patients (14-64 years old) were evaluated. Pretreatment IgE levels ranged from 18.2 to 8396 IU/mL, (mean IgE level was 1521 IU/mL). All 21 patients showed clinical and statistically significant improvement of their atopic dermatitis (p<0.00052). In conclusion, this study indicates that omalizumab is effective in treating AD in patients with moderate to severe persistent allergic asthma.

Comorbidity is a better predictor of impaired immunity than chronological age in older adults.

OBJECTIVES: To determine whether high level of comorbidity, measured using a standardized instrument, can predict impaired immunity in older adults. SETTING: Geriatric outpatient Clinic and Nursing Home Care Unit of Veterans Affairs Greater Los Angeles Healthcare System. PARTICIPANTS: Fifteen men aged 51 to 95 with varying levels of chronic illness. MEASUREMENTS: Disease burden was measured using the Cumulative Illness Rating Scale (CIRS) and immunity using proliferation of T cells induced by phytohemagglutinin (PHA) and production of interleukin (IL)-12, a proinflammatory cytokine that promotes T helper cell-dependent immune response, and IL-10, a cytokine that inhibits T helper cell-dependent immune response, in response to mitogenic stimulation of peripheral blood mononuclear cells. RESULTS: With increasing comorbidity (increase in CIRS score) in older adults, there is a proportional decrease in immune response (decrease in T cell proliferation and IL-12 production and increase in IL-10 production in response to PHA stimulation). Neither immune response nor CIRS score was significantly correlated with chronological age in this sample of older adults with varying degrees of chronic illness. CONCLUSION: This study demonstrates that the level of comorbidity correlates with the magnitude of immune response in older adults and suggests that the CIRS could be used to determine the magnitude of impaired immunity in older adults with different specific illnesses and different levels of severity.

Declining cell-mediated immunity and increased chronic disease burden.

BACKGROUND: The effects of chronic disease have been proposed as an explanation for conflicting results in studies of age effects on cell-mediated immunity. OBJECTIVE: To examine the hypothesis that declining cell-mediated immunity is more closely linked to chronic disease burden than to chronological age. METHODS: Fifty-eight elderly individuals were tested for delayed-type hypersensitivity (DTH) responses to Candida and tetanus antigens. Disease burden was quantified using the Cumulative Illness Rating Scale (CIRS). Higher CIRS scores reflect greater disease burden. Mean DTH response by age group (<71, 71-78, and >78 years) was compared with mean DTH response by CIRS score (<11, 11-15, >15). Total serum IgE levels were measured and similarly stratified by age and CIRS score. RESULTS: Mean Candida DTH responsiveness declined progressively with increasing disease burden (increasing CIRS score). Mean DTH responses were 7.78, 3.05, and 0.0 mm for CIRS scores less than 11, 11 to 15, and greater than 15, respectively. Candida DTH responses showed no progressive decline with advancing age. Mean DTH responses were 4.7, 3.5, and 5.0 mm in participants younger than 71, 71 to 78, and older than 78 years, respectively. Total serum IgE levels increased with advancing age. Mean total IgE levels were 182, 249, and 342 IU/mL in participants younger than 71, 71 to 78, and older than 78 years, respectively. No correlation was observed between mean total IgE levels and CIRS scores. CONCLUSIONS: An inverse relationship between Candida DTH response and CIRS score suggests that increased chronic disease burden is associated with diminished cell-mediated immune response. Advancing age did not predict a diminished DTH response in our patients. No relationship was observed between chronic disease burden and total serum IgE level.

Immune dysfunction in the elderly and its reversal by antihistamines.

The decline in immunity seen in the elderly is a significant contributor to disease burden. This decline has largely been attributed to alterations in T cell immunity and contributes to an overall increased risk and severity of infection in the elderly. A key component of T cell immunity involves antigen presentation, an event where an antigen is processed and presented to specific immune cells for destruction. This event has been found to be crucial to immune function. Recent research has focused on a key antigen presenting cell (APC), the dendritic cell (DC), and changes within its function associated with aging. DCs are considered to be the most professional APCs, and are responsible for the initiation and outcome of effector T cells and their resultant immune response. DCs capture antigens and undergo a maturation process and polarize into either type 1 dendritic cells (DC1) or type 2 dendritic cells (DC2), based upon their ability to favor a T helper1 (Th1) or T helper 2 (Th2) T cell response, respectively. Evidence suggests that in normal healthy adults, a Th1 type response predominates, and in frail elders, a Th2 response predominates. It has been proposed that this change from a predominately Th1 type to a predominate Th2 type response is a possible mechanism for age-associated immune dysfunction. In addition, recent research has focused on how histamine, an inflammatory mediator, promotes a Th2 response. Histamine has also been shown to polarize human DCs into Th2 cell-promoting effector DCs or DC2s. This has been shown to occur via interaction with the H2 receptor. Therefore, we theorize that use of an H2 selective antihistamine will reverse this polarization back to a Th1 type response and therefore improve immune function of the frail elderly.