The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma.

BACKGROUND: Vitamin D is hypothesized to have some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid (ICS). OBJECTIVE: To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers (ICS or ICS plus long-acting ß-agonist) on airway functions. METHODS: A randomized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period. Data on age, sex, body mass index, stage of asthma, serum total IgE, history of allergic rhinitis, atopic dermatitis, food allergy, and urticaria were collected. Spirometric parameters (forced expiratory volume in 1 second [FEV1] and ratio of FEV1 to forced vital capacity) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention. Patients were divided in 2 groups randomly. Both groups received asthma controllers (budesonide or budesonide plus formoterol) according to their stage, but the intervention group received vitamin D supplementation (100,000-U bolus intramuscularly plus 50,000 U orally weekly) in addition to asthma controllers. RESULTS: FEV1 improved significantly in both groups after 8 weeks, but no significant difference was found between the 2 groups at baseline (P = .20) or after 8 weeks (P = .99); however, a significant improvement was seen in the intervention group in the last 16 weeks, and FEV1 was significantly better in the intervention group than the other group after 24 weeks (P < .001). CONCLUSION: Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks. TRIAL REGISTRATION: irct.ir Identifier: IRCT201302079608N1.

Immunogenic Potential of the Mediterranean Fever Gene in Patients with Coronavirus Disease: A Cross-Sectional Study.

Background: In December 2019, an outbreak of pneumonia caused by the novel coronavirus disease 2019 (COVID-19) became a pandemic and caused a global health crisis. This study evaluates the immunogenic potential of the Mediterranean fever (MEFV) gene in patients with COVID-19. Methods: A cross-sectional study was conducted from March to April 2020 in various COVID-19 referral centers in Ardabil, Iran. Blood samples of 50 hospitalized patients with confirmed COVID-19 were evaluated for MEFV gene mutation using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and Sanger sequencing. Statistical analysis was performed using SPSS software, version 22.0. Results: Mutations of the MEFV gene were found in 6 (12%) of the patients. All mutations were heterozygous, and no homozygous or compound heterozygous forms were detected. The total mutant allele frequency was 6% and the carrier rate was 12%. The most common allele of the MEFV variant was E148Q, detected in 3 (6%) patients. No mutant variant of the MEFV gene was detected in deceased patients. None of the mutation carriers had familial Mediterranean fever (FMF) symptoms or a family history of FMF. Conclusion: MEFV gene mutations may have immunogenic potential in patients with COVID-19. A preprint version of this article has already been published at https://www.researchsquare.com/article/rs-69373/latest.pdf.

The Effect of Aspirin on Moderate to Severe Asthmatic Patients with Aspirin Hypersensitivity, Chronic Rhinosinusitis, and Nasal Polyposis.

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

Aspirin Sensitivity in Patients with Moderate to Severe Asthma.

Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38% for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9% of the patients with moderate asthma and 39.1% of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5% of cases, history of previous hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean pre-bronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma.

Characteristics, Etiology and Treatment of Pediatric and Adult Anaphylaxis in Iran.

Despite the increasing prevalence of anaphylaxis, there is little information about the characteristics and practice of healthcare providers in treating anaphylaxis, so this study was conducted to record the characteristics and therapeutic approaches of anaphylaxis from May 2012 until April 2015, the data of all patients diagnosed with anaphylaxis in the Allergy department of three referral university hospitals in Tehran, Iran were recorded. Thereafter, the demographics, clinical features, triggers and therapeutic approach were evaluated. This study investigated 136 individuals, 64 males (47%) between 6 months and 68 years old, as well as 72 others (52.94%) under 18 years of age (pediatric). The following were the most common organs involved: Skin 86.02% (pediatric 91.66% vs adult 79.68%), respiratory tract 51.47% (pediatric 43.05% vs adult 60.93%), cardiovascular 50.73% (pediatric 54.16% vs adult 46.87%), gastrointestinal 20.58% (pediatric 27.7% vs adult 12.5% ) and neurologic system 5.88% (only in adults). The following were the most identified causing foods 69 (50.37%)[42 pediatric (children) and 27 adults], drugs 34( 25%)[14 pediatric and 20 adults], idiopathic 16( 11.77%)[3 pediatric and 13 adults], insect sting 7( 5.15%)[3 pediatric and 4 adults] , exercise 6( 4.42%) [1 pediatric and 5 adults]. Milk, egg and wheat were the most common causative foods in pediatric cases but sesame, as well as egg and milk were the most common causes in adults. Epinephrine injection, auto injector epinephrine prescription as a discharging plan and referral to an allergist were: 10.78, 1.96 and 7.8 %, respectively. In this case series we found that, cutaneous, respiratory, cardiovascular and gastrointestinal complains were the most common manifestations and food, drug and idiopathic were the most common causes.In this study, the diagnosis of anaphylaxis, epinephrine subscription and referral to an allergist were significantly lower in comparison to other studies.

Evaluation of a new protocol for wheat desensitization in patients with wheat-induced anaphylaxis.

AIM: New approaches such as oral immunotherapy (OIT) may be useful in IgE-mediated anaphylaxis to wheat. PATIENTS & METHODS: 12 patients underwent OIT protocol that comprised of two phases: the first with semolina flour and the second with spaghetti. Total and specific wheat IgE were assayed by ELISA before and after OIT and 18 months later. Skin prick tests were also performed. RESULTS: Patients successfully tolerated 50 g of wheat. The median baseline total IgE was decreased after up-dosing phase and decreased after follow-up (p < 0.01). The median baseline wheat-specific IgE was increased after up-dosing and decreased after follow-up (p < 0.001). CONCLUSION: The efficiency and safety of our OIT protocol were shown on wheat allergic patients but further investigation is needed.

A gain-of-function mutation of STAT1: A novel genetic factor contributing to chronic mucocutaneous candidiasis.

Heterozygous gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) have increasingly been identified as a genetic cause of autosomal-dominant (AD) chronic mucocutaneous candidiasis (CMC). In this article, we describe a 33-year-old man who experienced chronic refractory candidiasis, recurrent otitis media, and pneumonia resulting in bronchiectasis, severe oral and esophageal candidiases with strictures associated with hypothyroidism and immune hemolytic anemia. His son also suffered from persistent candidiasis, chronic diarrhea, poor weight gain, and pneumonia that resulted in his demise because of sepsis. The immunological workup showed that an inverse CD4/CD8 ratio and serum immunoglobulins were all within normal ranges. The laboratory data revealed failure in response to Candida lymphocyte transformation test. In addition, by Sanger sequencing method, we found a heterozygous mutation, Thr385Met (T385M), located in the DNA-binding domain of STAT1, which was previously shown to be GOF. These findings illustrate the broad and variable clinical phenotype of heterozygous STAT1 GOF mutations. However, more clinical information and phenotype-genotype studies are required to define the clinical phenotype caused by AD STAT1 GOF.

LPS-Responsive Beige-Like Anchor Gene Mutation Associated With Possible Bronchiolitis Obliterans Organizing Pneumonia Associated With Hypogammaglobulinemia and Normal IgM Phenotype and Low Number of B Cells.

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs*2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency.