Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

Cypress Pollinosis: from Tree to Clinic.

Cypress (Cupressus sp.pl) is a genus within the Cupressaceae family. This family covers all of the Earth's continents except for Antarctica, and it includes about 160 species. The most important taxa for allergic diseases belong to five different genera: Cupressus, Hesperocyparis, Juniperus, Cryptomeria, and Chamaecyparis. Cupressaceae species share a common pollen type that can even include the genus Taxus (Taxaceae) when this plant is also present. As Juniperus oxycedrus pollinates in October, Cupressus sempervirens in January and February, Hesperocyparis arizonica (prev. Cupressus arizonica) in February and March, and Juniperus communis in April, the symptomatic period is long-lasting. Due to global warming, the pollination period tends to last longer, and there is a trend for Cupressaceae bioclimate niches to migrate north. In Mediterranean areas, C. sempervirens (Italian cypress or Mediterranean cypress) is by far the most common pollinating species. It accounts for half of the total pollination level. The group 1 major allergens belong to the pectate-lyase family, and members share 70 to 97% sequence homology within the different Cupressaceae. Group 2 allergens correspond to the polygalacturonase protein family, while group 3, a minor allergen, belongs to the family of "thaumatin-like proteins," a pathogenesis-related protein 5. Group 4 allergens are Ca++-binding protein (4 EF-hands). Aside from these four groups, about 15 other allergens have been reported. Prominent among these is a basic low-molecular mass cross-reactive allergen that was identified recently, and which is suspected to be involved in pollen food syndromes which are common with peach and citrus. The prevalence of cypress allergy in the general population ranges from 0.6 to 3%, depending on the degree of exposure to the pollen. Depending on the geographic area and the studied population, 9 to 65% of outpatients consulting an allergist may have sensitization to cypress pollen. Repeated cross-sectional studies performed at different time intervals have demonstrated a threefold increase in the percentage of cypress allergy around the Mediterranean area. Risk factors include a genetic predisposition and/or a strong exposure to pollen, and the natural history of cypress allergy allows identification of a subgroup of patients as allergic rather than atopic. Concerning the clinical expression, rhinitis is the most prevalent symptom, while conjunctivitis is the most disabling. Pharmacological treatment of cypress allergies is not different from that of other seasonal allergies. Immunotherapy has been used, initially by subcutaneous injections, but currently mostly through the sublingual route. Although clinical trials have included only a limited number of patients, it has proven effective and safe. Avoidance can be implemented at the individual level, as well as at the community level, through the use of alternative plants, low-pollinating cypresses, or by trimming hedges before pollination.

Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations.

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. OBJECTIVE: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. METHODS: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. RESULTS: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 µm [25th-75th IQR, 4.0-4.7 µm] and 3.9 µm [25th-75th IQR, 3.7-4.6 µm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. CONCLUSION: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.

Bronchial thermoplasty: a new therapeutic option for the treatment of severe, uncontrolled asthma in adults.

Bronchial thermoplasty is a young yet promising treatment for severe asthma whose benefit for long-term asthma control outweighs the short-term risk of deterioration and hospitalisation in the days following the treatment. It is an innovative treatment whose clinical efficacy and safety are beginning to be better understood. Since this is a device-based therapy, the overall evaluation of risk-benefit is unlike that of pharmaceutical products; safety aspects, regulatory requirements, study design and effect size assessment may be unfamiliar. The mechanisms of action and optimal patient selection need to be addressed in further rigorous clinical and scientific studies. Bronchial thermoplasty fits in perfectly with the movement to expand personalised medicine in the field of chronic airway disorders. This is a device-based complimentary asthma treatment that must be supported and developed in order to meet the unmet needs of modern severe asthma management. The mechanisms of action and the type of patients that benefit from bronchial thermoplasty are the most important challenges for bronchial thermoplasty in the future.