Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis

Background The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. Method The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013–2018) and the result of molecular diagnosis in patients enrolled for targeted and nextgeneration sequencing. Results Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. m

Global systematic review of primary immunodeficiency registries

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.Peer reviewe

Prevalence and Risk Factors of Allergic Rhinitis in Primary School Students of Isfahan, Iran

Background: Allergic rhinitis (AR) is one of the most common chronic diseases of childhood. Different studies have indicated an increasing prevalence of AR worldwide. The most common complaints of the patients are itching, tearing eyes, and rhinorrhea. The present study aims to assess the prevalence and risk factors of AR among 6–7-year-old children of Isfahan Province, Iran. Materials and Methods: This cross-sectional study conducted on 973 67-year-old primary school students of Isfahan Province in 2016. The study was conducted based on the International Study of Asthma and Allergies in Childhood questionnaire. Results: This study was conducted on 322 (33.1%) 6-year-old and 651 (66.9%) 7-year-old students. A total of 563 (57.9%) and 410 (42.1%) students were male and female, respectively. AR was diagnosed in 397 (40.8%) cases that 190 (47.8%) and 130 (32.7%) showed seasonal and permanent AR, respectively. A percentage of 44.7% of 6-year-old and 38.9% of 7-year-old (P = 0.04) students, 42.1% of males and 39% of females (P = 0.336), had AR; however, the percentages were not significant (P = 0.005). Exposure to smoking, plants, and domestic association with AR was not significant (P = 0.317, P = 0.863, and P = 0.253, respectively), but infancy breastfeeding association was significant (P = 0.015). Residence in the second area of Isfahan city was accompanied by higher prevalence of AR (P = 0.006). Conclusion: The prevalence of AR was considerably higher in Isfahan as one of the largest cities of Iran. It was significantly associated with age, infancy milk feeding, and area of residence but not with sex, smoking, plant, and domestic exposure

Effect of Fish Oil on the Level of Interferon Gamma on the Breast Milk of Atopic Mothers: A Randomized Clinical Trial

Background: The prevalence of allergic diseases is increasing worldwide. The effective role of omega-3 fatty acids in the maturation of immune system and protection against atopic diseases has been well discussed. However, previous studies revealed conflicting results. This study was conducted to investigate the effect of fish oil consumption by nursing atopic mothers on the level of interferon gamma (IFN-γ) in their breast milk and incidence of allergic disease in their infants. Methods: This randomized clinical trial was conducted on 94 atopic mothers, who were assigned to two equal groups receiving either 1000 mg fish oil capsules or placebo for 60 days after delivery. The breast milk was collected 120 days after delivery, and IFN-γ level was measured. The history of the symptoms of atopic disease in infants was collected from their mothers through ISAAC questionnaire; in addition, the infants’ growth was evaluated. Results: Sixty mother-infant pairs completed the trial. The mean values of IFN-γ in breast milk was higher in the fish oil group (1.11±1.15 Pg/ml) than in the placebo group (0.81±0.86 Pg/ml), but the difference was not significant (P=0.288). In addition, the incidence of allergic symptoms of infants was not significantly different between the two groups (P=0.84). Conclusion: In this trial, the consumption of fish oil by lactating mothers did not have a significant effect on IFN-γ level in their breast milk and the incidence of allergic symptoms in their infants. Future studies with longer follow-ups are necessary in this regard

Evaluation of Right Ventricular Function by Tissue Doppler Echocardiography in Asthmatic Children

BackgroundAsthma is the most chronic inflammatory disorder of the airways in children and asthmatic patients can experience cardiac dysfunction, pulmonary hypertension and finally cor pulmonale later in life. We aimed to investigate Right Ventricular (RV) functions in asthmatic children by conventional and tissue Doppler echocardiography (TDE).Materials and Methods Pulmonary function tests, conventional and TDE examinations were performed on 42 asthmatic and 42 age- and gender matched healthy controls subjects (n=42).Results Compared with healthy children the RV wall was statistically thicker among asthmatic patients (P= 0.01). Conventional echocardiography had not significant difference between cases and controls, but TDE had significant difference between these two groups. Peak E’ velocity, A’ velocity, E’/A’ ratio and S’ in lateral and medial sites of tricuspid annulus valve, were significantly differ from control group in our patients (

Comparison of Interleukin-33 serum levels in asthmatic patients with a control group and relation with the severity of the disease

Background: The relation between interleukin-33 (IL-33) and asthma is not precisely known yet. The present study set to compare the serum level of IL-33 in patients with asthma and controls and study the relation with the severity of disease. Methods: The serum level of IL-33 and total IgE in 89 asthmatic patients and 57 controls were analyzed. The association of levels of IL-33 with the severity of disease, levels of total IgE, measures of spirometry (forced expiratory volume in 1 s [FEV1]), age, sex, presence or absence of other allergic diseases, and the disease duration was evaluated. Results: Higher levels of IL-33 and total IgE were detected in asthmatic patients compared with controls (P = 0.0001 and P = 0.008, respectively). In the asthmatic group, a significant direct association of IL-33 with age (P = 0.02, R = 0.23) and with total IgE level (P = 0.003, R = 0.31) were observed, but there was no relationship between other variables. Comparison of mean level of IL-33 in different asthma groups concerning the disease severity showed the statistically significant difference between them and a significant increased serum level of total IgE was observed in more severe disease. The results showed a significant negative correlation between FEV1 and total IgE (P = 0.028, R = −0.23) and IL-33 level (P = 0.0001, R = −0.83). Conclusions: IL-33 is suggested as a new inflammatory marker of severe and refractory asthma. Therefore, it may be a unique therapeutic target in these patients

The Prevalence of Asthma in Children with Type 1 Diabetes Mellitus and Relationship between Control of Diabetes and Severity of Asthma

Background: Type 1 diabetes mellitus (T1DM) is by far the most common metabolic disease in children. Asthma is the most common chronic disease in pediatric population, and its prevalence has increased in the last decades. In this study, the prevalence of asthma among these children with T1DM has been described and its association with the demographic and clinical characteristics of Iranian children has been evaluated. Materials and Methods: A cross sectional study was carried out on children with T1DM who referred to pediatric endocrinology clinics of Isfahan University of Medical Sciences. The participants were classified as a group with asthma and the second group as diabetic children without asthma. After selection and evaluation of the diabetic patients with asthma, their glycemic status was evaluated three times in the past year. All data were analyzed using the SPSS version 23.0 statistical software package. Results: A total of 419 patients (49.4% male and 50.6% female) diagnosed with T1DM were included in the study. The mean age of patients at the time of recruitment was 12.65 ± 3.9 years with a range from 3.8 to 18 years. The mean of disease duration was 5.3 ± 2.7 years. Among all participants, asthma was detected in 24 children with T1DM (5.7%). Glycemic control was significantly poorer among asthmatic patients with diabetes compared with diabetic patients without asthma. Conclusion: The study demonstrated a lower prevalence of asthma among T1DM children rather healthy ones. Hence, diabetic child patients with asthma experience poorer glycemic control in comparison with T1DM patients without asthma

A multi-strain Synbiotic may reduce viral respiratory infections in asthmatic children: a randomized controlled trial

Background and objective: Asthma is a growing problem worldwide. Acute exacerbations impose considerable morbidity, mortality, and increased cost. Viral respiratory infections are the most common cause (80-85%) of pediatric asthma exacerbations and admissions to the hospital. The aim of this study was to determine the effect of a new synbiotic Lactocare® on viral respiratory infections and asthma exacerbations in asthmatic children. Methods: In this double blind, placebo-controlled, randomized clinical trial, 72 children with mild persistent asthma, aged between 6 and 12 years, were randomized to receive either Lactocare®, a Synbiotic containing 1 billion CFU/Capsule of Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, Lactobacillus acidophilus, Bifidobacterium infantis, Lactobacillus bulgaricus, and Fructooligosacharide (Zist Takhmir, Tehran, Iran) or placebo daily for 60 days. The primary outcome was the number of viral respiratory infections, and secondary outcomes were school absence, salbutamol and prednisolone usage, outpatient visits, and hospital admission for asthma. The outcomes were compared among study groups using the SPSS 11.5 program and the Mann Whitney and Fisher exact tests. Results: Of the 72 children who were enrolled with mild persistent asthma, 36 were assigned randomly to be treated with synbiotic and 36 with placebo. The number of viral respiratory infections was significantly higher in placebo group than the synbiotic group during the first month of intervention (0.74 ± 0.12 vs. 0.44 ± 0.1, p < 0.007) but not during the second month (0.5 ± 0.8 vs. 0.5 ± 0.8, p < 0.641). Considering the total duration of the study (two months), infection episodes also were significantly lower in the synbiotic group (0.92 ± 0.15 vs. 0.69 ± 0.11, p < 0.046). Salbutamol consumption was significantly lower in the synbiotic group, but there were no significant differences in school absenteeism, oral prednisolone use, outpatient visits, or hospital admissions. Conclusion: This new synbiotic (a mixture of seven probiotic strains plus fructooligosacharide may reduce episodes of viral infection in asthmatic children. Trial registration: This study is registered in Iranian Registry of Clinical Trials with registration number of IRCT201509234976N3. Funding: This research was supported financially by the Research Council of Mashhad University of Medical Sciences (Grant Number: 911048)