Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunodeficiency, partial albinism, recurrent infections, and progressive neurologic dysfunction. Unless patients undergo successful hematopoietic cell transplantation (HCT), a majority of them die during childhood because of an accelerated phase of immune dysfunction and hemophagocytic lymphohistiocytosis (HLH). Herein, we aim to describe the laboratory diagnosis, clinical manifestations, and genetic findings in three patients with CHS. Three patients with partial albinism associated with CHS were included in this study. Immunological screening tests were done. Leukocyte granules in peripheral blood smear (PBS) and hair shafts were examined. Subsequently, genetic analyses were performed by Whole Exome Sequencing (WES) followed by Sanger sequencing for all patients and their parents. Initial immunology screening tests were within normal limits. Light microscopy studies of patients' PBS showed giant granules in the leukocyte cytoplasm. Furthermore, there were evenly distributed melanin granules in the patients' hair shafts. Variant analysis of the LYST gene identified three splicing site defects: one known variant, c.7060-1G>A in intron 24, and two novel variants, c.2363+2T>C in intron 5, and c.10702-3A>G in intron 47. Hair shaft assay and PBS are rapid and suitable tests in early diagnosis and differentiation in CHS patients. WES results revealed 2 novel splice site variants that might contribute to earlier and more accurate diagnosis. This facilitates early enrolment of CHS patients in the HCT protocol-the optimal treatment path-and enables prenatal diagnosis for affected families.

BackgroundPrimary immunodeficiency diseases (inborn errors of immunity) with partial albinism are a group of autosomal recessive syndromes including Chediak Higashi Syndrome (CHS), Griscelli Syndrome type 2 (GS2), Hermansky-Pudlak Syndromes type 2 and 10 (HPS2, HPS10), Vici syndrome and P14/LAMTOR2 deficiency.MethodsTwenty-five patients including 10 CHS, 10 GS2, and 5 HPS2 were evaluated in this study within the last 10 years. Five cases with oculocutaneous albinism (OCA) and 5 healthy subjects without albinism were used as two control groups. Genetic analyses were performed by whole exome or panel sequencing or targeted Sanger sequencing. Subsequently, leukocyte granules in peripheral blood smear and hair shaft were examined as screening tests.ResultsGiant granules were only presented in the leukocytes cytoplasm of 10/10 CHS patients. The uneven cluster of pigments and giant melanin granules in hair samples were observed in 10/10 GS2 and 10/10 CHS patients, respectively. In both 5/5 OCA and 5/5 HPS2 patients, there were regular pigments in the middle of hair shafts. Genetic analyses were performed for all patients, revealing 7 novel variants in LYST gene for CHS patients and 4 novel variants in AP3B1 for HPS2 patients.ConclusionReceiving hematopoietic stem cell transplantation (HSCT) in a timely manner is crucial in CHS and GS2 patients; therefore, screening tests may provide a vital clue for early diagnosis in these patients. However, the final confirmation of CHS, GS2, and HPS2 disorders is done by genetic assay.

BackgroundAccording to the WHO’s recommendation for developing countries, Bacillus Calmette-Guerin (BCG) vaccination has been implemented in some countries as part of national vaccination programs at birth. Although it is generally considered safe, some complications may occur; including BCGitis (local) or BCGosis (systemic), ranging from mild like local abscesses to fatal impediments like osteomyelitis and disseminated BCG infection. This study aimed to determine the spectrum of inborn errors of immunity (IEI) in BCG-vaccinated neonates experiencing local or systemic complications.MethodsIn this cross-sectional study, we investigated Iranian children referred to the Immunology, Asthma, and Allergy Research Institute (IAARI) between 2007-2023 for suspected immunodeficiency. Medical history was recorded, and primary screening tests for immunodeficiency were conducted for all cases. For suspected cases, more advanced immunologic investigations were performed to reach a definitive diagnosis. Furthermore, the study incorporated the documented genetic findings of the patients under investigation. All patients with inborn error of immunity who had a history of BCG vaccine complications within the first year of vaccination were enrolled in the study.ResultsWe investigated 3,275 cases suspected of IEI, identifying197 patients with both IEI and BCG vaccine complications. Among these, 127 (64.5%) were male. Symptoms began at or before 3 months of age in 64.8% of the cases, and parental consanguinity was reported in 79.2%. Genetic diagnoses were confirmed in 108 patients. Of the 197 patients, 108 (54.8%) had BCGitis, while 89 (45.2%) experienced systemic complications (BCGosis). A family history of IEI, BCG-related complications, and unexplained deaths were observed in 20.3%, 12.2%, and 29.9% of cases, respectively. Furthermore, 46.2% had at least one of these three risk factors in their history.ConclusionsEarly BCG vaccine complications may indicate an underlying immunodeficiency, particularly when there is a positive family history of BCG complications, immunodeficiency, or unexplained deaths. Nation-wide vaccination protocols should address this issue by delaying inoculation to allow for immunological screening of suspected immunodeficient patients, thereby preventing BCG vaccine-related morbidity and mortality.

The purpose of this study is to investigate the effect of air pollutants and noise on the prevalence of childhood asthma in Tehran, Iran. The standardized questionnaire was completed by one of the parents of children aged 6-7 years or by adolescents aged 13-14 years. The asthma prevalence in ages 6-7 and 13-14 was found to be 8.8% and 17.44%, respectively. A significant positive association was observed between "ever wheezing" and monoxide carbon (CO) concentration (OR=1.84, 1.05-3.25 in 13-14 years), the occurrence of 4 to 12 wheezing attacks and sulfur dioxide (SO2) concentration (Odds Ratio [OR]=1.39,1.04-1.91) and particulate matter less than 2.5 micron (PM2.5) concentration (OR=1.38, 1.05-1.98 and OR=1.13, 0.98-1.39 in 6-7 and 13-14 years, respectively), as well as one night per week of sleep disturbances and nitrogen dioxide (NO2) concentration (OR=1.09, 1.03-1.16 in 6-7 years, respectively). It was also found that there was a significant interaction between the noise level and particulate matter less than 10 microns (PM10) level. Based on the findings, exposure to certain outdoor air pollutants and noise can affect the prevalence of asthma symptoms in residents of Tehran. The simultaneous presence of air pollutants and noise has an aggravating effect on the prevalence of asthma symptoms. Therefore, controlling sources of pollutants for reducing asthma symptoms is suggested.

The Article Abstract is not available.

BackgroundIn order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. MethodsSixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. ResultsThe diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. ConclusionPhysicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon-intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis.

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis. Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).

BACKGROUND:An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244.METHODS:Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens.RESULTS:Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization.CONCLUSIONS:The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test.

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.

Noise has been reported as one of the most important risk factors for asthma, but there are some disagreements. This study aimed to investigate the effect of road noise on asthma prevalence in adults. In the current study, 3172 adults were interviewed through the ECRHS standardized questionnaire in Tehran, the capital of Iran. Exposure to road noise was assessed considering distance of individual participants from the noise monitoring stations via the spatial analysis in GIS software. Logistic regression was used to assess the effect of noise on the symptoms of asthma. Findings showed a significant positive association between wheezing with dyspnea as the best marker for asthma and noise levels at daytime (OR 1.03; 0.98–1.05) and nighttime (OR 1.05; 0.84–1.09). Also, a significant positive association was obtained between daytime and nighttime noise levels and other asthma symptoms including wheezing, nocturnal chest tightness, nocturnal dyspnea, wheezing without cold, nocturnal cough, and asthma medication. Association between current asthma and noise level was not significant. There was a significant association between population age and current asthma prevalence (P = 0.001). Therefore, chronic exposure to road noise especially in the nighttime could increase asthma prevalence. So, control of noise sources can be suggested to diminish asthma in adults.

This Pocket Guide was developed by an ARIA and EAACI joint study group from a background paper of the ARIA-MASK study group and from the EAACI guidelines on allergen immunotherapy. Bousquet J, Pfaar O, Togias A, et al. (2019). ARIA Care pathways for allergen immunotherapy. Allergy 2019; 74: 2087–2102. Agache, Lau S, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: house dust mite-driven allergic asthma. Allergy, 2019;74:855-73. AIT is a proven therapeutic option for the treatment of allergic rhinitis, conjunctivitis, and/or asthma using sublingual (SLIT) or subcutaneous (SCIT) routes. However, AIT is more expensive than symptomatic treatments for allergic diseases (excluding biologicals). It is justified (i) in patients with rhinitis otherwise uncontrolled by symptomatic treatment or (ii) as an add-on to regular asthma treatment in controlled or partially-controlled asthmatic patients sensitised to house dust mites aiming to decrease asthma exacerbations, rescue and controller medication, and to improve quality of life. Care pathways are structured multi-disciplinary care plans detailing the key steps of patient care. They promote the translation of guideline recommendations to their application in clinical practice. Although many international and national AIT guidelines have been produced, this is the first care pathway for AIT. This pocket guide applies to sublingual (SLIT) and sub-cutaneous (SCIT) immunotherapy for allergic rhinitis. It has been revised by members from 65 countries (Figure 1). The decision to prescribe AIT should be based on relevant symptoms during allergen exposure, demonstration of sensitisation to the relevant allergens, and availability of good-quality extracts with proven efficacy and safety. Some allergen extracts are approved for marketing in the EU (list in annex) with some others also approved by national health agencies. For certain products, efficacy and safety have been demonstrated in appropriate clinical studies on adults and children. The extrapolation to untested products, allergens or a different population from the one evaluated in the trial is not appropriate and not in line with current guidelines as there is no class-effect in AIT. Both monosensitised and polysensitised patients can be treated. However, in the latter case, the most clinically relevant allergen(s) should be used when symptoms are clearly present with allergen source exposure and when allergy tests confirm clinical findings. Precision medicine aims at the customisation of healthcare, tailored to the characteristics of each individual patient. The stratification of patients into subpopulations is the basis of clinical decision making (Figure 2). In allergic diseases, patient stratification is required to: Propose the appropriate pharmacotherapy. Identify the most suitable candidates for AIT. Reduce the amount of time and resources needed to match the right patient to an optimal care management programme. Optimise costs as expensive therapeutic interventions are not necessary or suitable for all patients. Patient stratification may also help to improve the patient's engagement. Precise diagnosis with history, skin prick tests and/or specific IgE and, if applicable, component-resolved in vitro testing. In some cases, where the above-mentioned diagnostic tools do not allow for precise diagnosis, allergen provocation testing (nasal, ocular and, in some cases, bronchial) may be needed. Proven indications: Allergic rhinitis, conjunctivitis and/or asthma. Symptoms predominantly induced by the relevant allergen exposure. Patient stratification: Poor control of nasal or ocular symptoms despite optimal medications according to guidelines with documented adherence to treatment. Exceptions to requiring optimum symptomatic treatment prior to considering AIT include unacceptable side effects of the medications. Allergic asthma fully controlled under background asthma medication (see EAACI HDM-AIT GL) However, for partially controlled asthma, HDM-AIT may facilitate achieving asthma control (see EAACI HDM-AIT GL) Good clinical documentation of efficacy and safety for the AIT product with relevant trials. The patient's (and caregiver's) views represent an essential component. There are currently no in vivo or in vitro biomarkers validated for monitoring the efficacy of AIT although several potential candidates are currently being investigated. Apps can be used: To acquire real-world evidence to confirm the efficacy of AIT in situations where randomised controlled trials are difficult to perform. To assess air quality index including pollen exposure and air pollution. By physicians and patients for stratification of patients and follow-up. The selection of pharmacotherapy and AIT for patients with AR and/or allergic conjunctivitis may be better supported by evidence algorithms to aid patients and healthcare professionals jointly determine the treatment and its step-up or step-down strategy depending on rhinitis control (shared decision-making). A simple algorithm is proposed as an aid for physicians to determine the treatment of their patients (Figure 3). In the case of remaining ocular symptoms, add intra-ocular treatment. AIT is effective, has long-term beneficial effects after cessation, and may delay or prevent the onset of asthma. AIT can be initiated in children with moderate/severe rhinitis that is not controlled by appropriate medications according to guidelines. An algorithm for HDM-driven allergic asthma diagnosis and management is proposed by the EAACI guidelines. For patients with concomitant allergic rhinitis and sensitised to house dust mite—with persisting asthma symptoms despite low-moderate dose of inhaled corticosteroids—SLIT can be considered, provided FEV1 is >70% predicted. House dust mite SLIT should initially be considered as an add-on therapy to controller treatment, and reduction in asthma controllers should be performed gradually under the supervision of a physician. Immunotherapy is not indicated for the treatment of acute exacerbations, and patients must be informed of the need to seek medical attention immediately if their asthma deteriorates suddenly (Figure 4). One strength of AIT is that it has the potential to control all allergic diseases related to a specific allergen, including rhinitis, conjunctivitis and asthma. Local reactions: A typical reaction is redness and swelling at the injection site immediately or several hours after the injection. Sometimes, sneezing, nasal congestion or hives can occur. Systemic reactions: Serious reactions to injections are very rare and require immediate medical attention. Symptoms of an anaphylactic reaction can include swelling in the throat, wheezing or tightness in the chest, nausea and dizziness. The most serious reactions develop within 30 min after the injection, and patients are advised to wait in their doctor's surgery for at least 30 min after an injection. Severe bronchospasm can also occur, especially in patients where asthma is not controlled. Allergen drops or tablets have a more favourable safety profile than injections. The initial dose should be performed in the doctor's surgery, and patients are advised to remain in the surgery for at least 30 min after administration. Thereafter, SLIT can be administered at home once the first dose has been given under the supervision of a physician. Allergic reactions: The majority of patients will experience mild local reactions of the oropharyngeal passage. This is usually controlled by predosing with an antihistamine 30 min before the administration of SLIT. Sometimes, sneezing, nasal congestion or hives can occur. Anaphylaxis is rarely described. In some countries, SLIT tablets include a warning about possible severe allergic reactions, and adrenaline auto-injectors are routinely recommended. This is not the case in Europe. IAgache is an Associate Editor Allergy and CTA. CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne-Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith-Kline, advisory role in scibase. IA reports personal fees from Hikma, Roxall, Astra Zeneca, Menarini, UCB, Faes Farma, Sanofi, Mundipharma, Bial, Amgen, Stallergenes. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. VC reports personal fees from ALK, Allergy Therapeutics, LETI, Thermofisher, Merck, Astrazeneca, GSK. TC reports grants and personal fees from Stallergenes. PD reports personal fees from ALK-Abello, Stallergenes-Greer, Astra Zeneca, GlaxoSmithKline, Mylan, Sanofi. SD reports personal fees and non-financial support from ALK Abello, personal fees from Adiga, Biomay, Allergopharma, Anergis, Allergy Therapeutics. TH reports personal fees from GSK, Mundipharma, Orion Pharma. SH reports other from ALK-Abelló, other from ALK-Abelló. EH reports personal fees from Sanofi, Novartis, GSK, AstraZeneca, Circassia, Nestlè Purina. JCI reports personal fees from Faes Farma, Laboratorios Casasco Argentina, Abbott de Ecuador, EuroFarma Argentina. MJ reports personal fees from ALK-Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, HAL, during the conduct of the study; personal fees from Astra-Zeneka, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Janssen, Medimmune, Chiesi,. LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO-BV, GPA, EAACI. PK reports personal fees from Adamed, Berlin Chemie Menarini, Boehringer Ingelheim, AstraZeneca, Lekam, Novartis, Polpharma, GSK, Polpharma, Sanofi, teva. VK reports other from GSK, non-financial support from Mylan, AstraZeneca, Dimuna, Norameda. SL reports personal fees from DBV, Sanofi Aventis, Allergopharma, ALK, Nutricia, Bencard. EM reports personal fees from Sanofi, Novartis, AstraZeneca and Chiesi. JM reports personal fees and other from SANOFI-GENZYME & REGENERON, NOVARTIS, ALLAKOS, MITSUBISHI-TANABE, MENARINI, UCB, ASTRAZENECA, GSK, MSD, grants and personal fees from MYLAN-MEDA Pharma, URIACH Group. MO reports personal fees from Hycor Diagnostics, Thermo Fisher Phadia. YO reports personal fees from Torii Pharmaceutical Co., Ltd., Shionogi Pharmaceutical Co.,Ltd. OP received research grants from Inmunotek S.L., Novartis and MINECO and has received fees for giving scientific lectures or participation in Advisory Boards from: Allergy Therapeutics, Amgen, AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Sanofi-Genzyme and Stallergenes. NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. OP reports grants and personal fees from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl-Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non-financial support from Boehringer Ingelheim, non-financial support from Philips. MR is on the Advisory board- A. Menarini - Speaker - Astra Zeneca, Novartis, Sanofi, Mylan. FSRreports speaker and advisory fees from AstraZeneca, Novartis, Sanofi, GSK, Teva and Lusomedicamenta. GR reports payment to his Institution from Allergo Pharma. BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. JS reports grants and personal fees from Sanofi, personal fees from GSK, Novartis, Astra Zeneca, Mundipharma, Faes Farma. GS reports personal fees from ALK, and leds on the BSACI Rhinitis Guidelines and lead for EUFOREA on Allergic Rhinitis. PSG reports personal fees from Allergopharma, ALK, grants from Bencard, grants and personal fees from Stallergenes. JS reports personal fees from Mylan, F2F events. ATB reports grants and personal fees from Teva, AstraZeneca, GSK Sanofi, Mundipharma, personal fees from Bial, Novartis. MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. MW reports personal fees from ALK-Abello, Allergopharma, AstraZeneca, Bencard, Genzyme, GlaxoSmithKline, HAL Allergy, LETI, Meda Pharma, Novartis, Sanofi, Stallergenes, Teva. DW reports other from Optinose, ALK, Sanofi; past Co-Chair of the Joint Task Force on Practice Parameters of the AAAAI and ACAAI. Second author of a recently published practice parameter on Rhinitis. MW reports other from Aralez (Medexus), Pediapharm, Pfizer, Astra Zeneca, GSK, Alk. MZ reports personal fees from Takeda. TZ reports and Organizational affiliations: Commitee member: WHO-Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA). Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI). Head: European Centre for Allergy Research Foundation (ECARF). Secretary General: Global Allergy and Asthma European Network (GA2LEN). Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). Countries with Pocket Guide members Proposed Flow of Precision Medicine approach in allergic diseases. *examples of exceptions: Thunderstorm-induced asthma, patient with moderate rhinitis and severe asthma during pollen season Treatment algorithm using visual analogue scale (VAS) for adolescents and adults AIT, allergen immunotherapy; VAS, visual analogue scale. Algorithm for AIT in asthma

Exosomes are extracellular vesicles that are involved in intracellular communication and different biological processes. Recently, the importance of microRNAs (miRNAs) in exosomes has been considered as biomarkers in asthma diagnosis. This study aimed to determine the expression of selective miRNAs from plasma-derived exosomes in moderate and severe asthmatic patients compared with healthy controls. Forty-six subjects including 22 patients with severe and mild to moderate allergic asthma and 24 healthy controls have entered this study. MiRNAs were extracted from the plasma exosomes and selective miRNAs (miR-21, miR-16, miR-Let7, miR-148a, miR-155, miR-125, miR-150, miR146a, miR-223, miR-126) expressions levels were determined; using quantitative polymerase chain reaction (qPCR). In this study, we found a significant up-regulation of miR-223 and miR-21 in moderate asthmatic patients compared to the healthy controls (p=0.002, p=0.006). MiR-223 and miR-21 had the probability of 83% and 76% diagnosis estimation in moderate asthmatic patients respectively. Therefore, they could be used as biomarkers in these patients. No expression of miR-125, miR-126, and miR-155 was found in plasma exosomes by qPCR in this study. The other miRNAs had no significant expression between different groups. Based on our findings, miR-223 and miR- 21 may be considered biomarkers or used for targeted immunotherapies in asthma.

Purpose This study aimed to determine the impact of MI on self-efficacy, beliefs about medicines and medication adherence among adolescents with asthma. Method This randomized controlled trial conducted on 52 adolescents with asthma referring to the Pediatric Medical Center in Tehran, Iran. They were randomly assigned to the control and intervention groups. The educational intervention consisted of 3 one-hour sessions per week, which was held individually in the areas of medication adherence, beliefs about medicines and self-efficacy. Four validated questionnaires including demographic characteristics, medication adherence, self-efficacy and beliefs about medicines were completed by self-report both before the MI and 40 days after the end of the intervention. Results In the baseline, the two groups were homogeneous in terms of demographic characteristics and outcome measures. At the post-test, the mean scores of the three outcome measures in the intervention group were reported higher compared to the scores in the control group (p < 0.05). The difference between the mean scores in medication adherence, beliefs about medicines and self-efficacy in the post-test between the two groups, even with the elimination of the effect pre-test scores, were significant (p < 0.05). Conclusions The results of this study showed that MI can be effective in improving medication adherence, beliefs about medicines, and self-efficacy. Practice implications The primary goal in the treatment of patients with asthma is asthma control by using corticosteroids. MI is one of the interventions that can simultaneously provide motivation, readiness, beliefs about medicine and self-efficacy for behavioral changes (medication adherence) in patients with asthma.

Air pollution is defined as the risk factors for asthma. This study aimed to investigate the effect of exposure to ambient air pollution and prevalence of asthma in adults. This cross-sectional study was done between November 2015 and February 2016. The asthma prevalence was surveyed in 3172 adults between 20 and 44 years old in Tehran, Iran. Face to face interview and standardized questionnaire (European Community Respiratory Health Survey (ECRHS)) were used for data gathering. Concentrations of air pollutants in the whole city of Tehran were obtained from Tehran Air Quality Control Company (AQCC). Air pollution exposure assessed by the spatial analysis based on GIS method. The effect of ambient air pollution on the asthma symptoms was assessed with the crude and adjusted logistic regression. Results were reported as odds ratios (OR) with 95% confidence interval (CI). Results showed that the asthma prevalence in adults in Tehran was 11.73%, higher than the average prevalence of asthma in the whole country equal to the 8.9%. The prevalence of asthma in males (6.43%, n=204) was significantly higher than females (5.26%, n=167), but this difference was not significant (P = 0.29). A significant positive association was observed between the asthma prevalence and the concentration of CO (OR 1.64; 1.26 to 1.85) and PM10 (1.04; 1.01 to 1.08) (P <0.05). Finally, we concluded that exposure to some air pollutants can affect the asthma prevalence in adults. Therefore, control of air pollution is recommended to reduce the asthma in Tehran metropolis.

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Background Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients. Methods Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations inSERPING1were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger. Results Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T>C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA. Conclusion Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4.

Asthma is a complex disease with diverse clinical manifestations ranging from mild to severe. Despite existing guidelines for asthma recognition and treatment, still a proportion of patients stay uncontrolled. Combinational therapy which comprises inhaled corticosteroids (ICS) and a long acting B2 adrenreceptor agonist (LABA) has been suggested to control asthma. In this study T-bet expression was attested in CD4 T cells treated with Fluticasone Furoate (FF), Vilanterol (V) and FF/V combination in severe asthmatic patients compared to patients with moderate asthma and healthy controls using Immunocytochemistry (ICC). First, CD4 T cells were isolated from PBMCs of 12 patients and controls using CD4 T cell isolation kit. Subsequently, isolated CD4 T cells were cultured with FF, V and FF/V for 1 h. To accomplish ICC, cells were incubated with anti-T-bet antibody, and then stained with HRP-bound secondary antibody. T-bet expression was evaluated using light microscopy. Statistical analyses were performed using R 3.5.2 software and visualized by ggplot2 3.1.0 package. Significant increasing in T-bet expression was seen in CD4 T cells from patients with moderate asthma treated with FF and FF/V. Suggesting conclusion would be distinct mechanisms responsible for severe asthma and moderate asthma in the patients and the needs for novel therapies. Further molecular studies in different asthma phenotypes would be instructive for asthma treatment.

In light of various supports of prodigious figures in the field of immunology and allergy, the subject area has been faced a great leap during the last century. The current state of the discipline owes an abundant appreciation for the scholars motivated in escalating the true nature of the science, who left no stone unturned in improving the general common sense and understanding of the human knowledge in general, and immunology and allergy in particular. Professor Reza Farid Hosseini is among the dignitaries who invested his life and energy on weaving the tapestry of the immunology and allergy. He delivered a great deal of influence on the field by his ethical devotion to science and was a significant contributor in the realms of the human immune system. His presence drastically rehabilitated the place of the Immunology in Iran, and the current paper seeks to review the personal and academic life of Professor Reza Farid Hosseini in honor and appreciation for his in-depth involvement in the field. The paper summarizes Professor Farid’s childhood, school, and higher education, compilations, and translation of books, his contribution to the research both inside and outside of Iran, and scientific activities of Dr. Farid Hosseini.