Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. METHODS: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. RESULTS: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. CONCLUSION: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Primary immunodeficiency disorders in Iran: update and new insights from the third report of the national registry.

BACKGROUND: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. METHODS: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. RESULTS: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). CONCLUSIONS: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

The effect of calcium and phosphorus supplementation on metabolic bone disorders in premature infants.

OBJECTIVE: To determine the impact of calcium and phosphorus on radiological and biochemical characteristics of osteopenia in premature infants. METHODS: The randomised clinical trial study was conducted at Valie-e-Asr Hospital of Zanjan city, Iran, from December 2010 to June 2011. It involved monitoring 40 premature neonates over a period of six months. The babies, who were fed with breast milk and 400 units of vitamin D daily, were randomly divided into two equal groups. One group received supplement of calcium and phosphorus. Serum calcium, phosphorus and alkaline phosphatase levels as well as growth parameters (including weight, height, and head circumference) were measured every two weeks. At the end of the study, wrist X-ray was done for evaluation of osteopenia. Data was analysed using SPSS 16. RESULTS: Radiological changes, characteristic of osteopenia, were found in 8 (40%) cases and 13 (65%) controls (p < 0.113). The mean of weight, length and head circumference increased significantly from second to sixth week during follow-up (p < 0.0001). Phosphorus and alkaline phosphatase activity decreased significantly from second to sixth week of follow-up (p < 0.02, p < 0.01 respectively). However, repeated measurement analyses did not show significant effect of intervention in biochemical and growth parameters in the trial group. CONCLUSION: The study didn't show significant effect of calcium and phosphorus on prevention of osteopenia and improvement of growth. Further studies of longer duration and with different doses of supplement are recommended.

Comparing Budesonide and Fluticasone Propionate in Children with Moderate to Severe Asthma: A Pilot Randomized Controlled Trial.

The aim of asthma treatment is to reduce airway inflammation by avoiding environmental triggers and using daily anti-inflammatory medications. This study aimed to compare the effects of fluticasone propionate (FP) and budesonide (Bud) on the clinical symptoms and control of asthma in children with moderate to severe asthma. In this open-label study, children with moderate to severe asthma were randomly selected to receive either FP 250 mcg or Bud 400 mcg for 3 months. Asthma control test scores were measured in both groups monthly. The clinical symptoms, drug adherence, and rescue medication were also evaluated. A total of 50 patients with ages between 4 and 7 years old were included in the study (25 cases received Bud and 25 cases received FP). Asthma control test scores, daily and nocturnal symptoms, and cough rates were significantly improved in both groups. The average asthma control scores for the fluticasone group were 21.68±3.32 in the second month and 24.84±2.67 in the third month, whereas the budesonide group had scores of 18.52±3.32 and 22.48±4.12 during the same periods. These variances were statistically significant. Additionally, the requirement for salbutamol use was notably reduced in the fluticasone group compared to the budesonide group throughout all three months. The efficacy of fluticasone propionate in decreasing the need for rescue medication and enhancing asthma control test scores was markedly superior to that of budesonide.

The Effect of Salt Space on Clinical Findings and Peak Expiratory Flow in Children with Mild to Moderate Asthma: A Randomized Crossover Trial.

The asthma treatment and control might be associated with significant burden on family and community' thus exploring other therapeutic plans could be desirable. The aim of this study was to investigate the effect of salt space on clinical findings and peak expiratory flow rate among children with asthma. In this randomized crossover trial, 34 patients aged 6-14 years old with mild to moderate asthma were selected and randomly divided into two groups. The first group went through a period of salt therapy by staying in the salt room for one hour, three times a week for 3 consecutive weeks and then was under observation for three weeks. This process was reversed for the second group (three weeks under observation followed by salt therapy). The wash-out period was one week. During the study, the morning and evening peak expiratory flow (PEF), the frequency of coughing, wheezing, dyspnea and use of rescue medications were measured. Salt therapy had a significant effect on raising the morning and evening PEF in the second week in both groups (p=0.028 and p=0.032, respectively). However, there was no significant effect on PEF variabilities' cough' wheezing, dyspnea, and the frequency of rescue medication (p>0.05). No side effect was observed during salt therapy. This study showed the significant effect of salt therapy on PEF rate of the patients in the second week. However, further studies with different frequency and time of salt therapy on respiratory disorders are recommended.

Evaluation of serum & salivary IgA in patients with type 1 diabetes.

BACKGROUND: Diabetes mellitus is a common immune mediated disorder. The aim of the present study is to evaluate the level of serum and salivary IgA levels in patients with Type 1 diabetes. MATERIAL AND METHOD: In this case control study, serum and salivary IgA levels of patients with diabetes type 1 and similar non diabetes subjects were measured. Age, gender, duration of diabetes and the last HbA1c level of diabetic patients were also studied. Data was analyzed by SPSS software. RESULTS: Two hundred and fifty subjects (126 diabetics and 124 non diabetics) were enrolled in the study. The mean value of serum IgA in patients with Type 1 Diabetes and controls was 1.77± 1.55 g/lit and 2.39± 1.52 g/lit, respectively. The mean salivary IgA level in diabetics and controls was 276 ± 162.5 40 µg/ml and 129 ± 112.2 40 µg/ml, respectively. Selective IgA deficiency was detected in two (1.6%) and three(2.4%)cases of diabetic and control group; respectively (p=0.68). We found low salivary IgA level in 44.4% diabetic and 33.9% control (p=0.08). There was no significant correlation between serum and salivary IgA level. There was also significant association between serum IgA levels with age. Salivary IgA was significantly correlated with HbA1c level. But considering gender, duration of diabetes we didn't find any association. CONCLUSION: We didn't find any significant difference in serum and salivary IgA level among diabetic and non diabetics and also, no association between serum and salivary IgA levels.

Efficacy and safety of inhaled and intranasal corticosteroids.

Inflammation is an important phenomenon in allergic disorders and corticosteroid drugs since their anti inflammatory properties have a pivotal role in improvement, control and relieving the symptoms and signs of asthma, allergic rhinitis, atopic dermatitis and many other inflammatory disorders. Nevertheless, the prescription of these drugs might be associated with some unwanted reactions such as hyperglycemia, hypertension, Cushing's syndrome, adrenal insufficiency and growth failure. In recent decades administration of intranasal and inhaled corticosteroids instead of systemic parenteral or oral drugs reduced some of these concerns during treatment of patients and enable them to receive the effective and safer kind of therapy in acute or chronic inflammatory disorders of nose and airways. In this article the properties of inhaler (ICS) and intranasal corticosteroids (INCS) were reviewed.

Comparison of Problem-based Learning With Lecture-based Learning.

BACKGROUND: Problem-based learning (PBL) is one of the most commonly used educational methods in medical schools of different countries. By working through this method, students think critically, generate ideas, and acquire the knowledge and skills required to become a doctor. OBJECTIVES: This study aimed to compare problem-based learning with lecture-based learning in the education of medical students. MATERIALS AND METHODS: This crossover interventional study was conducted on 40 medical students in pediatric ward of Zanjan University of Medical Sciences. All of the students were enrolled in the study and divided into two groups by simple randomization. Then two topics in pediatric courses were chosen. One of the topics was presented as LBL for the first group and as PBL for the second group. The other topic was presented as PBL for the first group and as LBL for the second group. RESULTS: The median score of the exam was higher in the intervention group compare to the control group for both topics. However, the difference was not statistically significant. Students preferred problem-based learning over lecture-based learning because of motivation boost, a higher quality of education, knowledge retention, class attractiveness, and practical use. CONCLUSIONS: Students' knowledge was similar in both methods.

Relation between asthma and body mass index in 6-15 years old children.

Childhood asthma and obesity are significant public health problems. Most prospective studies suggest that obesity increases the risk of asthma. But, some authors did not found this association. In this study the association between asthma and body mass index (BMI) was investigated. This case-control study was conducted on 200 asthmatic children aged 6-15 years and 200 children without asthma. The criteria for asthma diagnosis and its classification were on the basis of National Asthma Education and Prevention Program (NAEPP). BMI of patients and controls were also measured and BMI grater than 85% and 95% were defined as overweight and obese respectively. The data was analyzed by SPSS software. The BMI among the asthmatic children (17.9 kg/m2) was higher than the BMI among the non-asthmatics (16.5 kg/m2), P=0.0001. This relationship was significant in both males and females. 18% of asthmatic children were classified as overweight and 13.5% of them were obese versus 7.5% and 6% respectively in non asthmatics (P=0.0001). However, there was no significant relationship between severity, duration of asthma, kind of medication and BMI in children with asthma (P>0.05). Result of this study showed that there is an association between asthma symptoms and obesity in children. Therefore, any attempts for weight control in asthmatic children might be beneficial.

Efficacy of sublingual swallow immunotherapy in children with rye grass pollen allergic rhinitis: a double-blind placebo-controlled study.

Specific local immunotherapy has been recently introduced as an alternative to classic subcutaneous immunotherapy in treatment of allergic rhinitis. In this study, the effects of sublingual immunotherapy (SLIT) on symptoms and medication score and skin prick test evaluation of patients with allergic rhinitis were investigated.In this placebo controlled trial, twenty four patients aged 5-18 years old with grass pollen induced rhinitis and sensitive to rye grass by positive skin prick test received randomly sublingual extract of rye grass or placebo for 6 months. Symptom and medication scores and adverse effects of SLIT were assessed during treatment. Skin prick test induced wheal at the beginning and the end of therapy were also measured. Data were analyzed with SPSS software.We found significant reduction of symptoms in intervention group from 21st week of immunotherapy (p<0.05). Medication scores were also reduced after 16th week (p<0.05), adverse effects were low and insignificant in both groups. Erythema induced diameter with skin prick test for grass and rye grass was significantly reduced in SLI group after immunotherapy.This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumes. We recommend this therapy as a safe therapy in patients with allergic rhinitis.

Nasal eosinophilia as a marker for allergic rhinitis: a controlled study of 50 patients.

Eosinophils are the principal effector cells involved in the pathogenesis of allergic inflammation. We conducted a study to investigate the validity of the nasal smear examination for detecting eosinophilia in patients with allergic rhinitis. Our study group was made up of 50 patients with allergic rhinitis and 50 age- and sex-matched controls without allergic rhinitis. Smears were obtained from nasal secretions in both groups and then fixed, stained, and studied under light microscopy. Statistical analysis revealed that the odds ratio for eosinophilia positivity in nasal smears in the rhinitis group was 25.61 with a 95% confidence interval of 8 to 78. The sensitivity, specificity, positive predictive value, and negative predictive value of this test were 74, 90, 88, and 77%, respectively. We conclude that the nasal eosinophilia test is highly specific and moderately sensitive in diagnosing allergic rhinitis, and that it therefore can be used as an easy, noninvasive, and inexpensive procedure for screening patients and for conducting epidemiologic studies of this disorder.

Comparison of Effectiveness between Beclomethasone Dipropionate and Fluticasone Propionate in Treatment of Children with Moderate Asthma.

Asthma is a common chronic disease. Beclomethasone dipropionate (BDP) and Fluticasone propionate (FP) are 2 inhaled corticosteroids that frequently be used in treatment of patients with asthma. In this study, the effectiveness of BDP and FP in management of asthmatic children was investigated. In this trial, 50 children with moderate persistent asthma were randomly selected to receive either BDP 600 µg or FP 500 µg for 3 months. Pulmonary function tests were measured in both groups at the beginning of study and monthly after treatment. Daily and night symptoms and consistency of drugs were also measured. There was significantly better FEV1 in patients receiving FP compared with the BDP group (P < 0.01). There was also statistically significant difference in patients receiving FP compared with BDP group in increment of FVC, FEV1/FVC, FEF25-75 (P < 0.005). Night symptoms were significantly improved in the FP group from the first month (P = 0.001), while improvement of daily symptoms in this group compared with the BDP group was found from the second month (P = 0.001). Although symptoms and pulmonary function tests results were improved in both groups receiving either FP or BDP, this study suggested that FP was more effective than BDP in controlling moderate asthma in children.

A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City.

The prevalence of atopic disease in recent decades has been dramatically increased. It has been suggested that BCG vaccination may protect against development of allergic diseases.The purpose of this study was to identifying relation between scar of BCG vaccine and atopy. This cross-sectional study was done in 1000 children, 10-15 years of age, in Zanjan city. One thousand children (501 girls and 499 boys) were recruited in this study, 137, 121 and 141 cases of asthma, atopic dermatitis and allergic rhinitis, respectively were detected.Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013), atopic dermatitis (P<0.01), and atopy (P<0.01). We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.