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Published By S. Karger Ag

1423-0097, 1018-2438

Author(s):  
Kensuke Fukumitsu ◽  
Hirono Nishiyama ◽  
Yoshihiro Kanemitsu ◽  
Norihisa Takeda ◽  
Ryota Kurokawa ◽  
...  

<b><i>Introduction:</i></b> Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV<sub>1</sub>) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. <b><i>Methods:</i></b> We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β<sub>2</sub>-agonists (ICS/LABA) was initiated. FEV<sub>1</sub> and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV<sub>1</sub> (ΔFEV<sub>1</sub>) were analyzed. Patients with a ΔFEV<sub>1</sub> &#x3c;–20 mL were defined as “poor-responders.” <b><i>Results:</i></b> FEV<sub>1</sub>, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV<sub>1</sub> was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV<sub>1</sub> on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (<i>p</i> = 0.009). <b><i>Conclusion:</i></b> Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV<sub>1</sub>.


Author(s):  
Ariadna Soto ◽  
Matías Perrone Sibilia ◽  
Vanesa Roxana Sánchez ◽  
Nadia Arcón ◽  
Valentina Martin ◽  
...  

<b><i>Background:</i></b> We have previously showed rTgPI-1 tolerogenic adjuvant properties in asthma treatment, turning it a promising candidate for allergen-specific immunotherapy. This therapy is an alternative treatment to control asthma that still presents several concerns related to its formulation. rTgPI-1 contains independent inhibitory domains able to inhibit trypsin and neutrophil elastase, both involved in asthma pathology. <b><i>Objectives:</i></b> In view of the need to design rational therapies, herein we investigated the contribution of the different inhibitory domains in rTgPI-1 therapeutic effectiveness. <b><i>Methods:</i></b> BALB/c mice were rendered allergic by intraperitoneal OVA-alum sensitization and airway challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with OVA combined with the full-length recombinant protein rTgPI-1 or its truncated versions, Nt (containing trypsin-inhibitory domains) or Ct (containing neutrophil elastase-inhibitory domains). Afterward, mice were aerosol re-challenged. <b><i>Results:</i></b> Asthmatic mice treated with the neutrophil elastase- or the trypsin-inhibitory domains separately failed to improve allergic lung inflammation. Only when all inhibitory domains were simultaneously administered, an improvement was achieved. Still, a better outcome was obtained when mice were treated with the full-length rTgPI-1. <b><i>Conclusions:</i></b> Adjuvant ability depends on the presence of all its inhibitory domains in a single entity, so it should be included in potential asthma treatment formulations as a full-length protein.


Author(s):  
Jana Sakakini ◽  
Carla Irani ◽  
Rana Bikai ◽  
Gretta Sahyoun ◽  
Souheil Hallit ◽  
...  

<b><i>Introduction:</i></b> Food allergy (FA) is a global health problem with an ongoing rise in prevalence, especially in developed countries. It has been reported to be most prevalent in children, although cases in adults have been increasing as well. FA may lead to life-threatening clinical manifestations. Data in Lebanon and the Middle East are limited. To our knowledge, few studies tackled its prevalence in children in this region. <b><i>Aim:</i></b> This study aims at determining self-reported prevalence of FA in schoolchildren (ages 3–17 years) in Lebanon and describes its characteristics. <b><i>Method:</i></b> Throughout this cross-sectional study, 5 schools from 3 different governorates in Lebanon (Beirut, Mt. Lebanon, and Beqaa) were contacted to participate and 5,312 questionnaires were sent out to be completed by the parents and sent back to the school during May 2019. <b><i>Results:</i></b> 2,610 questionnaires were collected (49.13%). A hundred and forty-eight (6%) children reported to have FA, 58% were males. 80% of them were breastfed, 51% were diagnosed between the ages of 2 and 14 years. Common allergens included cow’s milk and milk products (22.46%), fruits and vegetables (16.58%), eggs (8.02%), and nuts (5.88%). Allergic symptoms included skin reactions (45.08%), gastrointestinal (GI) symptoms (29.53%), respiratory symptoms (14.51%), and systemic symptoms (10.88%). 82% of the population with FA has sought professional advice, out of which 54% were confirmed by a physician. Common methods of diagnosis were IgE test (35.71%), food elimination (27.92%), and skin prick test (18.83%). χ<sup>2</sup> analysis has shown that a higher percentage of children with FA had skin reactions (58.8%, <i>p</i> = 0.033) and GI symptoms (30.41%, <i>p</i> = 0.047). A higher percentage of children with allergies were breastfed. No relation between the presence of FA and delivery mode was observed. <b><i>Conclusion:</i></b> This study has shown that the self-reported prevalence of FA among Lebanese schoolchildren is 6%, and it was correlated with skin and GI symptoms. The most common allergen was cow’s milk. A higher proportion of children with FA were breastfed. No association between the mode of delivery and FA was found. Larger studies are needed to confirm the above findings.


Author(s):  
Pinar Gokmirza Ozdemir ◽  
Velat Celik

<b><i>Introduction:</i></b> Several statements and position papers on the management of childhood asthma and allergies during the COVID-19 pandemic have been published of late. The aim of this study was to evaluate the knowledge and awareness of pediatricians and family physicians regarding the management of asthma and allergic rhinitis during the pandemic according to recently published updated guidelines. <b><i>Method:</i></b> We conducted an online survey among pediatricians and family physicians in Turkey, using a questionnaire designed to evaluate 4 items: (1) the relationship between COVID-19 infection risk and pediatric asthma/allergic rhinitis and medications used in treatment; (2) the follow-up and management of asthma/allergic rhinitis according to published updated recommendations; (3) pediatricians’ and family physicians’ observations and perceptions of treatment compliance and the attitudes of their pediatric asthma patients; and (4) pediatricians and family physicians’ attitudes to using telehealth in the follow-up and management of pediatric asthma patients during the pandemic. <b><i>Results:</i></b> A total of 346 participants responded to the survey. The relationship between the risk of COVID-19 and asthma was known by less than 25% of the participants. More than 33% of family physicians and 20% of pediatricians were unaware that asthma medication does not lead to a susceptibility to COVID-19 infection; 55% of family physicians and 48% of pediatricians thought that patients showed better compliance with asthma controller medication; over 33% of pediatricians and approximately 50% of family physicians stated that they could not distinguish between an asthma attack and lung involvement in COVID-19 infection; of the respondents, over 75% stated that they prefer face-to-face visits with patients, even in situations that do not require a physical examination. <b><i>Conclusion:</i></b> The overall knowledge and awareness of pediatricians and, especially, family physicians regarding the management of pediatric asthma/allergic rhinitis during the pandemic is not at a satisfactory level. There is an urgent need to inform them about updated recommendations appearing in recent guidelines published by allergy organizations.


Author(s):  
Taissa M. Kasahara ◽  
Sudhir Gupta

<b><i>Background:</i></b> The regulatory CD8<sup>+</sup> T (CD8<sup>+</sup> Treg) cells play an important role in immune tolerance and have been implicated in several human autoimmune diseases. In this context, follicular helper T (T<sub>FH</sub>) cells contribute by controlling the antibody production. In mice, CD8<sup>+</sup> Treg cells control the number and function of T<sub>FH</sub> cells however the role of human CD8<sup>+</sup> Treg cells on the differentiation of naive CD4<sup>+</sup> T cells into T<sub>FH</sub> cells has not been studied. <b><i>Objectives:</i></b> Here, we evaluated the ability of human CD183<sup>+</sup> CD8<sup>+</sup> Treg cells to suppress T<sub>FH</sub> cell differentiation in vitro. <b><i>Methods:</i></b> Activated CD183<sup>+</sup>CCR7<sup>+</sup>CD45RA<sup>−</sup>CD8<sup>+</sup> Treg and CD183<sup>+</sup>CD25<sup>high</sup>ICOS<sup>+</sup>CD8<sup>+</sup> Treg cells were sorted and cocultured with naïve CD4<sup>+</sup> T cells under T<sub>FH</sub> differentiation condition. The differentiation of T<sub>FH</sub> cells was evaluated by flow cytometry. <b><i>Results:</i></b> Our results showed that activated CD183<sup>+</sup>CD8<sup>+</sup> Treg cells upregulated the expression of Forkhead box P3 transcription factor, inducible T-cell co-stimulator (ICOS), and CD25 compared to CD183<sup>−</sup>CD8<sup>+</sup> T cells. The CD183<sup>+</sup>CD25<sup>high</sup>ICOS<sup>+</sup>CD8<sup>+</sup> Treg cells suppressed T<sub>FH</sub> cell differentiation and CD4<sup>+</sup> T cell proliferation in vitro which was not observed when CD183<sup>+</sup>CCR7<sup>+</sup>CD45RA<sup>−</sup>CD8<sup>+</sup> Treg were cocultured with naïve CD4<sup>+</sup> T cells under T<sub>FH</sub> cell differentiation condition. <b><i>Conclusion:</i></b> These results suggest that CD25<sup>high</sup>ICOS<sup>+</sup>CD183<sup>+</sup>CD8<sup>+</sup> Treg cells may regulate autoimmune and inflammatory responses mediated by T<sub>FH</sub> cells.


Author(s):  
Ruoyun He ◽  
Yujuan Chen ◽  
Xiaoer Chen ◽  
Binfan Yuan

<b><i>Introduction:</i></b> Allergic rhinitis (AR) is an immune disorder and also a risk factor of asthma. microRNAs (miRNAs) are implicated in autoimmune diseases, including RA. This study investigated effect of miR-181a-5p on regulatory T (Treg)/ T-helper (Th) 17 immune imbalance in AR. <b><i>Methods:</i></b> A murine model of AR was established and treated with lentivirus modified miR-181a-5p. The allergic symptoms of mice were examined. The contents of Th17-related cytokines (interferon [IFN]-γ and interleukin [IL]-6), Treg-related cytokine (IL-10), and Treg-specific nuclear transcription factor (Foxp3) in nasal mucosa and lung tissues were determined. The proportion of Treg and Th17 cells was analyzed by flow cytometry. The level of ovalbumin-specific immunoglobulin E in the serum, and the contents of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and IFN-γ, IL-6, and IL-10 in nasal lavage fluid were measured. The targeting relationship between miR-181a-5p and high mobility group box chromosomal protein 1 (HMGB1) was verified. HMGB1 and receptor for advanced glycation end products (RAGE) expression in RA were determined, and the interaction between HMGB1 and RAGE was detected. <b><i>Results:</i></b> miR-181a-5p expression was reduced in AR mice. miR-181a-5p overexpression attenuated allergic behaviors, alleviated Treg/Th17 imbalance, and delayed asthma development. HMGB1 and RAGE were elevated in AR mice. miR-181a-5p targeted HMGB1, and HMGB1 bound to RAGE, while miR-181a-5p overexpression reduced the binding between them. Activating HMGB1/RAGE reversed the protective effect of miR-181a-5p overexpression on AR and induced the development of asthma. <b><i>Conclusion:</i></b> miR-181a-5p overexpression reduced the binding of HMGB1 and RAGE by inhibiting HMGB1, thus alleviating Treg/Th17 immune imbalance and blocking AR from developing into asthma.


Author(s):  
Xian-hui Zhang ◽  
Ying-an Zhang ◽  
Xin Chen ◽  
Peng-yan Qiao ◽  
Li-yun Zhang

<b><i>Background:</i></b> The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. <b><i>Methods:</i></b> PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by <i>I</i><sup><i>2</i></sup> statistic and <i>p</i> value from the Cochrane Q test. <b><i>Results:</i></b> Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of −0.40 (95% CI: −0.66 to −0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of −0.1 (95% CI: −0.39 to 0.19). <b><i>Conclusion:</i></b> The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.


Author(s):  
Elide Anna Pastorello ◽  
Alessandro Toscano ◽  
Giuseppe Scibilia ◽  
Chrysi Stafylaraki ◽  
Carlo Maria Rossi ◽  
...  

<b><i>Introduction:</i></b> Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. <b><i>Methods:</i></b> With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. <b><i>Results:</i></b> Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (<i>p</i> &#x3c; 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (<i>p</i> = 0.0017), a higher risk to be wheat allergic (<i>p</i> &#x3c; 0.0001), a higher severity of the reactions (<i>p</i> &#x3c; 0.00001) and a higher association with some cofactors, namely alcohol (<i>p</i> &#x3c; 0.0005) and physical exercise (<i>p</i> = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (<i>p</i> &#x3c; 0.0001), with a higher probability of patients being asymptomatic (<i>p</i> &#x3c; 0.0001) and being sensitized to other foods, in particular to nuts and cereals (<i>p</i> &#x3c; 0.00001). <b><i>Conclusions:</i></b> Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it’s more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance.


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