IL-5 Exposure in utero Increases Lung Nerve Density and Causes Airway Reactivity in Adult Offspring.
Am J Respir Cell Mol Biol. 2019 Dec 10;:
Authors: Lebold KM, Drake MG, Hales-Beck LB, Fryer AD, Jacoby DB
Asthma is characterized by airway hyperreactivity and inflammation. In the lungs, parasympathetic and sensory nerves control airway tone and induce bronchoconstriction. Dysregulation of these nerves results in airway hyperreactivity. Humans with eosinophilic asthma have significantly increased sensory nerve density in airway epithelium, suggesting type-2 cytokines and inflammatory cells promote nerve growth. Similarly, mice with congenital airway eosinophilia also have airway hyperreactivity and increased airway sensory nerve density. Here, we tested whether this occurs during development. We show that transgenic mice that overexpress interleukin-5 (IL-5), a cytokine required for eosinophil hematopoiesis, give birth to WT offspring that have significantly increased airway epithelial nerve density and airway hyperreactivity that persists into adulthood. These effects are caused by in utero exposure to maternal IL-5 and resulting fetal eosinophilia. Allergen exposure of these adult WT offspring results in severe airway hyperreactivity, leading to fatal reflex bronchoconstriction. Our results demonstrate that fetal exposure to IL-5 is a developmental origin of airway hyperreactivity, mediated by hyperinnervation of airway epithelium.
PMID: 31821769 [PubMed - as supplied by publisher]
The Impact of Interleukin (IL)-33 Gene Polymorphisms and Environmental Factors on Risk of Asthma in the Iranian Population.
Lung. 2019 Dec 09;:
Authors: Matloubi M, Ranjbar M, Assarehzadegan MA, Fallahpour M, Sadeghi F, Soleyman-Jahi S, Janani L
BACKGROUND: Airway epithelial cells secrete Interleukin-33 in response to the different allergens. Several single nucleotide polymorphisms (SNP) of this cytokine have been reported to be involved in the development of asthma. We conducted this study to evaluate the impact of the two most common SNPs of the IL-33 gene (rs1342326 and rs3939286) and environmental factors on the susceptibility to asthma in the Iranian population.
SUBJECTS AND METHODS: In this study, we enrolled 126 asthmatics patients and 300 age, sex-matched controls. Genotyping was performed by real-time PCR using the TaqMan SNP genotyping assay. Moreover, total serum IgE level, eosinophil count, and skin prick test were accomplished and complete history was taken from all the participants.
RESULTS: The frequencies of mutant genotypes in both SNPs were significantly higher in asthmatics than controls. C/C genotype of rs1342326 [OR (95% CI) 2.50 (1.33-4.69)] and A/A genotype of rs3939286 [OR (95% CI) 2.18 (1.05-4.52)] were associated with higher risk of asthma development. While A/C+C/C genotype of rs1342326 was more prevalent in mild asthma [OR (95% CI) 2.36 (1.14-4.89)], G/A+A/A genotype of rs3939286 was associated with increased risk of moderate and severe asthma [OR (95% CI) 2.53 (1.30-4.94)].
CONCLUSION: This study revealed that both IL-33 SNPs were associated with an increased risk of asthma. The rs1342326 was associated with atopic, mild and adult-onset asthma and a higher level of eosinophils in peripheral blood. However, rs3939286 was more frequent in moderate and severe asthma. Moreover, rs3939286 was associated with non-atopic and childhood-onset asthma.
PMID: 31820077 [PubMed - as supplied by publisher]
A Case of Serum Sickness-Like Reaction in an Adult Treated with Omalizumab.
Mil Med. 2019 Dec 09;:
Authors: Weiss SL, Smith DM
Omalizumab has been safely used to treat asthma and urticaria. We report a case of serum sickness-like reaction in a patient treated with omalizumab for chronic idiopathic urticaria/angioedema. An adult female experienced episodic urticaria/angioedema without repeatable trigger, ultimately receiving diagnosis of chronic idiopathic urticaria/angioedema. After initial treatment, attempts with escalating cetirizine and montelukast doses were unsuccessful due to sedation; she began treatment with subcutaneous omalizumab 150 mg monthly. Urticaria frequency partially improved after two injections; therefore, the dose was increased to 300 mg after four treatments. Several days after first 300 mg dose, she reported abdominal cramping, fatigue, fever, lymphadenopathy, and arthralgia. Aside from mild thrombocytosis, inflammatory markers were unremarkable, as were evaluations for infection, autoimmunity, and malignancy. Omalizumab was held with eventual improvement in symptoms, which did not return after discontinuation. Omalizumab is a helpful medication in treating atopic conditions, with at least theoretical risk of immune complex formation and tissue deposition causing serum sickness-like reaction. Although early publications showed very low adverse event rates, there have now been reports of serum sickness-like reactions in children and adults treated for asthma and urticaria. Determining true incidence is difficult, given rarity and non-specific nature. Previous reports described symptoms with initiation of medication, reproducible after reintroduction. While it remains to be determined which factors increase risk for serum sickness-like reaction to omalizumab, our report of an urticaria patient who exhibited symptoms with increasing dose contributes insight into the discussion regarding this adverse effect of an otherwise well-tolerated and important medication.
PMID: 31819972 [PubMed - as supplied by publisher]
Familial Success in Allergen Desensitization.
Allergy Rhinol (Providence). 2019 Jan-Dec;10:2152656719890315
Authors: Rowane M, Shilian R, Jhaveri DK, Tcheurekdjian HH, Sher TH, Hostoffer R
Introduction: Allergic rhinitis (AR) is a widely prevalent immunoglobulin E-mediated inflammatory nasal condition resulting from reexposure to an allergen in a sensitized individual. The genetic associations behind AR and other allergic conditions have been studied. However, familial success with AR therapies, specifically allergen desensitization through subcutaneous immunotherapy (SCIT), has never been reported in the literature. Pharmocogenetics has been gradually applied to link heritable genetic variants with drug responses, such as intergenic region variants APOBEC3B and APOBEC3C and β2-adrenergic receptor and glycoprotein ADAM33 polymorphisms as predictive biomarkers for biologic treatment response in asthma. We provide the first reported survey of familial success with SCIT.
Methods: We administered a month-long, institutional review board-approved (20190493) questionnaire to 200 adult patients receiving SCIT in a suburban allergy/immunology practice. The anonymous survey inquired about demographics, target allergens for their SCIT, current symptom improvement on SCIT, and family history of allergies and SCIT management.
Results: Twenty-six percent (52 of 200, 26%) SCIT patients reported familial success with the same allergy treatment modality. AR diagnosis and symptom improvement from SCIT was similar among previous/same (18 of 52, 38%; 26 of 52, 54%) and subsequent (10 of 52, 21%; 19 of 52, 40%) generations of family members. A combination of seasonal and perennial allergies was most prevalent (81%) among this population.
Conclusion: In a subpopulation of SCIT patients, there appears to be a familial success rate with this allergen desensitization treatment. This is the first reported pharmocogenetic evidence of assessing hereditary influence on effective AR therapy. Understanding pharmacogenetic associations involved with SCIT may improve allergists' recommendations for this treatment option.
PMID: 31819808 [PubMed]
Severe Atopic Dermatitis In Spain: A Real-Life Observational Study.
Ther Clin Risk Manag. 2019;15:1393-1401
Authors: Sicras-Mainar A, Navarro-Artieda R, Armario-Hita JC
Objective: To determine the epidemiology and characterize the treatment prescribed for severe atopic dermatitis (AD) in children/adults in usual clinical practice.
Methods: Observational, retrospective study made through review of medical records of Spanish patients aged ≥6 years. Patients diagnosed with severe AD who required care between 2013 and 2017 were included. The study groups were: 6-12 years; 13-18 years; and > 18 years. Patients were followed for 5 years. The main measurements were the prevalence of AD, comorbidity and treatment duration. Statistical significance was established as p <0.05.
Results: We included 2323 patients with severe AD. The overall prevalence was 0.10% (95% CI: 0.09-0.11%) and was 0.39%, 0.23% and 0.07% in the 6-12 years, 13-18 years and >18 years age groups, respectively (p <0.001), the percentage of males was 58%, 48.6% and 39%, respectively, and general comorbidity was 0.1, 0.2 and 0.9 points, respectively (p <0.001).The most frequent comorbidities were asthma in 49.0%, 44.9% and 20.8%, respectively (p <0.001), and anxiety in 79.7%, 65.8% and 67.3%, respectively (p <0.001). Oral corticosteroids were administered in 97.3%, 90.9% and 81.7%, respectively (concomitant-medication). Cyclosporine (45.3%), azathioprine (15.9%) and methotrexate (9.0%) were the most frequently prescribed drugs; biologic agents were administered in 5.8% of patients (for AD).
Conclusion: In AD the presence of comorbidities was significant, especially in the psychological, immunoallergic and cardiovascular areas. Cyclosporine was the most widely used immunosuppressant. There was a degree of variability in the use and duration of the treatments prescribed.
PMID: 31819466 [PubMed]