Allergen exposure can confound the management of asthma. To understand the potential mechanisms by which allergens increase the steroid requirements in atopic asthmatics, we examined the effects of allergens on glucocorticoid receptor (GCR) binding affinity and glucocorticoid (GC) responsiveness of peripheral blood mononuclear cells (PBMC) from atopic asthmatics. A significant reduction (p < 0.001) in the GCR binding affinity (Kd) was observed in ragweed-allergic asthmatics during ragweed pollen season compared with PBMC obtained before and after ragweed season. In vitro effects of allergen on PBMC GCR Kd were also examined by incubating PBMC from atopic asthmatics with allergen (ragweed and cat) versus Candida albicans. GCR binding affinity was significantly reduced after incubation with ragweed (p < 0.001) or cat allergen (p < 0.001) compared with baseline or C. albicans stimulation. This effect was limited to atopic asthmatics in that in vitro cat allergen incubation for 48 h failed to significantly alter GCR binding affinity in nonasthmatic, atopic individuals. These allergen-induced reductions in GCR binding affinity also rendered the PBMC less sensitive to the inhibitory effects of hydrocortisone and dexamethasone on allergen-induced proliferation (p < 0.01). To test the hypothesis that allergen-induced alterations in GCR binding affinity were cytokine-induced, we examined the effects of interleukin-2 (IL-2)and IL-4 neutralization using anticytokine antibodies. Addition of both anti-lL-2 and anti-lL-4 antibodies resulted in a significant (p < 0.001) inhibition of allergen-induced alterations in GCR binding affinity. Furthermore incubation with cat allergen induced significantly higher concentrations of IL-2 (p = 0.03) and IL-4 (p = 0.02) by PBMC from atopic as compared with nonatopic subjects. Our current observations suggest that allergen exposure may contribute to poor asthma control by reducing GCR binding affinity in mononuclear cells. This appears to be mediated through IL-2 and IL-4. These findings may have important implications for novel approaches to the treatment of poorly controlled asthma.

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Recent studies indicate that chronic asthma is associated with a spectrum of glucocorticoid receptor (GCR) binding abnormalities that are cytokine-inducible. These GCR abnormalities may contribute to poor asthma control and failure to respond to glucocorticoid (GC) therapy. The purpose of this study was to determine whether GCR defects are associated with poorly controlled asthma, and whether diminished GCR binding is reversible following a course of GC therapy. We enrolled 12 patients with poorly controlled asthma characterized by nocturnal awakening with cough or wheezing, AM FEV1 < 70%, or FEV1 variability of > 25% requiring a short course of high dose GC therapy. GCR binding affinity was measured in peripheral blood mononuclear cells using a radioligand binding assay before and after the GC course. Spirometry, serum cortisol, eosinophil cationic protein (ECP), and soluble IL-2 receptor (sIL-2R) levels were also performed before and after the GC course. At baseline, all subjects had airflow obstruction that significantly improved (median FEV1 increased from 65.0% to 89.5% of predicted, median FEV1/FVC ratio increased from 0.60 to 0.72) with therapy. A diminished GCR binding affinity at baseline was noted with an elevated median dissociation constant (Kd) of 29.0 nM (interquartile range at the 25th and 75th percentile [IQ] of 22.3 and 44.5 nM) compared with normal controls (Kd 8.0 nM [IQ 7.0, 9.2]). Following the GC course, a significant decrease in the Kd was seen. Serum ECP and sIL-2R levels at baseline were elevated, with serum ECP demonstrating a significant reduction following the GC course.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Few studies have examined how developing obesity in early adulthood affects the course of asthma. Objective We analyzed lung function and asthma impairment and risk among non-obese children with asthma, comparing those who were obese in young adulthood to those who remained non-obese. Methods Post-hoc analysis of 771 subjects with mild-moderate asthma who were not obese (pediatric definition, body mass index (BMI) <95th percentile) when enrolled in the Childhood Asthma Management Program at ages 5–12 years. Subjects were then followed to age ≥ 20 years. For visits at ages ≥ 20 years, spirometry values as percent predicted and recent asthma symptom scores and prednisone exposure were compared between 579 subjects who were non-obese at all visits and 151 who obese (adult definition of BMI ≥ 30 kg/m2) on at least one visit (median number of visits when obese = 4, IQR 2–7). Results Compared to participants who were non-obese (BMI 23.4 ± 2.6 kg/m2), those who became obese (BMI 31.5 ± 3.8 kg/m2) had significant decreases in FEV1/FVC (p<0.0003) and FEV1 (p = 0.001), without differences in FVC (p=0.15) during visits at ages ≥ 20 years. For each unit increase of BMI, FEV1 percent predicted decreased by 0.29 (p=0.0009). The relationship between BMI and lung function was not confounded by sex or BMI at baseline. Asthma impairment (symptom scores) and risk (prednisone use) did not differ between the two groups. Conclusion Becoming obese in early adulthood was associated with increased airway obstruction, without impact on asthma impairment or risk.

Background: Past studies have evaluated the association of various comorbidities with bipolar disorder. This study analyzes differences in the prevalence and association of medical and psychiatric comorbidities in bipolar patients by gender. Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). Using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study population to comprise those with a primary diagnosis of bipolar disorder and then obtained information about comorbidities. The differences in comorbidities by gender were quantified using chi-square tests and the logistic regression model (odds ratio (OR)). Results: Hypertension (20.5%), asthma (12.5%) and hypothyroidism (8.1%) were the top medical comorbidities found in bipolar patients. Migraine and hypothyroidism were seen three times higher in females (OR = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn’s disease (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR = 1.663) compared to males. Conclusion: Women with bipolar disorder have a much higher medical comorbidity burden than men and may highly benefit from an integrated team of physicians to manage their condition and improve their health-related quality of life.

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The occurrence of atopic disease throughout the world is subject to many variables. Differences in methodology and diagnostic criteria for measuring the incidence could account for some disparities, but they cannot explain all of them. Despite our increasing knowledge of the atopic diseases, improved treatments, and early diagnosis, the incidence and prevalence of asthma, allergic rhinitis, and atopic dermatitis continue to rise. Ongoing research into the etiology and potential risk factors for atopic diseases could lead to the early diagnosis, effective treatment, and prevention.

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