M. Conway

Nasal polyps : effects of seasonal allergen exposure

Nasal polyps are characterized by chronic eosinophilic inflammation and often coexist with rhinitis and asthma. Many patients with polyps have no detectable allergy, and it is considered that allergy, at least in many cases, is not relevant to polyp to pathogenesis. To explore the association of nasal polyps with allergy, 16 patients with polyps and ragweed allergy (PRW +) and 16 patients with polyps who were not allergic to ragweed (PRW-) were compared with patients without polyps, 16 who were allergic to ragweed (NPRW +) and 16 who were not allergic to ragweed (NPRW-), before and during the ragweed season. The level of ragweed allergy was comparable in the PRW+ and NPRW+ populations as determined by ragweed skin test wheal diameter, ragweed IgE RAST percent binding, and total serum IgE. Symptom scores before the ragweed season recorded on visual analog scales for the symptoms of blockage, sneezing, decreased smell, itch, postnatal drip, and runny nose were high in patients in the PRW+ and PRW- groups and did not change during ragweed season. Mean symptom scores were low in the NPRW+ group before ragweed season and increased during the season to levels similar to those of patients in the PRW+ and PRW- groups. Preseason nasal lavage albumin concentration was higher in subjects with polyps than those without polyps (58.5, 98) versus (13.6, 15 micrograms/ml) (p = 0.02) and did not change significantly in any group with seasonal exposure. Data are presented as mean, 1 SD; comparisons are made with unpaired t tests.(ABSTRACT TRUNCATED AT 250 WORDS)

TNF-α Dysregulation in Asthma: Relationship to Ongoing Corticosteroid Therapy

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy.

Immunoreactivity profile of peripheral blood mononuclear cells from patients with ragweed-induced allergic rhinitis

Background Seasonal rhinitis is manifested by a series of nasal symptoms in response to exposure to seasonal allergens including ragweed pollen. Understanding its immunological mechanisms may help to better manage the disease.

Review of the effect of internet therapeutic intervention in patients with type 1 and type 2 diabetes.

The use of the Internet has changed the way health care professionals manage diabetes, with platforms now available allowing patients to upload self-monitoring of blood glucose data and share with their health care provider (1). Previous studies have established the efficacy of Internet blood glucose monitoring systems (1–3). It is now our standard of care to offer an Internet blood glucose monitoring system to patients. We currently have 1,100 patients enrolled and have outcome data on the first 409 patients. Of the 409 patients, 388 had HbA1c at baseline and at least one subsequent HbA1c determination within 9 months. HbA1c values from 3–9 months were averaged to generate follow-up data. The relationship of reporting frequency and HbA1c change was determined by dividing patients into frequent reporters, who reported more than once per month, and infrequent reporters. Patients were instructed to upload self-monitoring …

Clinical and nasal irrigation fluid findings in perennial allergic rhinitis.

Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen. Patients with PAR were then treated for 2 weeks with the topical nasal steroid. The only marker that discriminated patients with perennial allergic rhinitis and healthy subjects was eosinophil count (EO%): correspondingly 14.01 ± 5.8 and 0.18 ± 0.09, (M ± SD). Difference between the studied groups did not depend on the time of irrigation, baseline or 1-hour. EO% was also the only marker of a clinically successful treatment with the nasal steroid, 14.01 ± 5.8 and 0.87 ± 0.4, before and after treatment respectively. We conclude that EO% is the most sensitive inflammatory marker of perennial allergic rhinitis, and that baseline nasal irrigation can be used to study nasal mucosal inflammation.

IL-10 inhibits allergen-specific TH2 cytokine production by human peripheral blood mononuclear cells from patients with ragweed allergies

~ A IL-10 Inhibits Allergen-Specific TH2 Cytokine Production by 1 ~jl-lr Human Peripheral Blood Mononuclear Cells From Patients With Ragweed Allergies J Sun, Susanna Goncharova, M Conway, A Dalrymple, Elizabeth C Cates, Martin R Stampfli, B Wong, Susan Waserman, Manel Jordana McMaster University, Hamilton, ON, Canada Type 2 polarized T cells and their effector cytokines play a central role in allergic diseases. The objective of this study was to investigate whether ILl0, a cytokine with powerful immuno-suppressive activities, inhibits Th2 cytokine production by peripheral blood mononuclear cells (PBMC) from patients with ragweed allergies. The patients were assessed by skin prick test and clinical history, and PBMC were isolated from these ragweed allergic individuals and non-atopic controls prior to pollen season. PBMC were stimulated with a ragweed pollen extract and cytokine synthesis was measured in culture supematants. Spontaneous production of IL-5 and IL-13 varied with each individual and was not significantly different between the atopic and non-atopic group. In ragweed allergic patients, addition of ragweed extract to the cell culture markedly enhanced levels of IL-5 and IL-13. In contrast, PBMC from non-atopic controls did not respond to ragweed stimulation. Both spontaneous and allergen-induced IL-5 and IL13 production were significantly inhibited by recombinant human IL10. IL10 also suppressed Th2 cytokine production induced by PMA, a T cell polyclonal stimulator. Interestingly, IL-4 synthesis could not be detected in any of the samples tested. We are currently assessing the impact of IL-10 on chemokine production. We also extracted RNA from cultured cells at 3h, 6h, 12h, 24 h, 72h, and 5 days and are assessing the expression of chemokine receptors and co-stimulatory molecules using real time quantitative PCR. Our findings in samples collected prior to pollen season will be compared to samples being generated during pollen season. In summary, PBMC from ragweed allergic individuals produce significant levels of IL-5 and IL-13 in response to ragweed stimulation. This response is inhibited by exogenous IL-10. Thus, our results further the notion that IL10 has therapeutic potential in allergic diseases.