Global warming and implications for epithelial barrier disruption and respiratory and dermatologic allergic diseases.

Global warming has direct and indirect effects, as well as short- and long-term impacts on the respiratory and skin barriers. Extreme temperature directly affects the airway epithelial barrier by disrupting the structural proteins and by triggering airway inflammation and hyperreactivity. It enhances tidal volume and respiratory rate by affecting the thermoregulatory system, causing specific airway resistance and reflex bronchoconstriction via activation of bronchopulmonary vagal C fibers and upregulation of transient receptor potential vanilloid (TRPV) 1 and TRPV4. Heat shock proteins are activated under heat stress and contribute to both epithelial barrier dysfunction and airway inflammation. Accordingly, the frequency and severity of allergic rhinitis and asthma have been increasing. Heat activates TRPV3 in keratinocytes, causing the secretion of inflammatory mediators and eventually pruritus. Exposure to air pollutants alters the expression of genes that control skin barrier integrity and triggers an immune response, increasing the incidence and prevalence of atopic dermatitis. There is evidence that extreme temperature, heavy rains and floods, air pollution, and wildfires increase atopic dermatitis flares. In this narrative review, focused on the last 3 years of literature, we explore the effects of global warming on respiratory and skin barrier and their clinical consequences.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease.

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Characteristics of the patients with asthmarhinitis multimorbidity.

Introduction: Asthma and allergic rhinitis frequently coexist and have been regarded as a single airway disease. Clinical features of patients with asthmarhinitis multimorbidity may change depending on the allergic sensitization pattern. The aim of our study is to determine the frequency, type, and characteristics of the patients with asthma-rhinitis multimorbidity. Materials and Methods: Patients who were followed up with a diagnosis of asthma between 2015 and 2020 in our clinic were included in our crosssectional study. Sociodemographic and clinical characteristics of the patients, rhinitis symptoms, and atopy status according to the results of the skin prick test, and sp IgE were recorded from the patient files. Result: Asthma-rhinitis multimorbidity was seen in 138 (113 F/25 M) out of 405 asthmatics and the mean age was 45.51 ± 13.56 years. They were younger and the age of onset of asthma was earlier than asthma patients without rhinitis. The rate of concomitant allergic rhinitis (AR) was 25.9%, and the rate of non-allergic rhinitis (NAR) was 8.1% in the entire group. There was no difference between patients with AR and NAR in terms of comorbidities such as NSAID sensitivity, nasal polyps, chronic rhinosinusitis, and bronchiectasis but, gastroesophageal reflux disease was more common in those with NAR than in those with AR (39.4%, 18.1%, respectively, p= 0.01). Of 105 asthmatic patients accompanied by allergic rhinitis, 41 (39.09%) were monosensitized, and 64 (60.95%) were polysensitized. House dust mites were found to be the most common responsible allergen in monosensitized patients. Sensitization to two allergens was the most common pattern among polysensitized patients, and mites and mold association was the most frequent. Patients with monosensitized allergic rhinitis had more severe asthma and a higher rate of NSAID sensitivity than polysensitized patients (p= 0.03, p= 0.04, respectively). There was no difference in the control level, frequency of eosinophilia, and other comorbidities. Conclusions: Our patients with asthma-rhinitis multimorbidity were mostly polysensitized. The most responsible allergen for the sensitization was house dust mites, regardless of whether the patient was monosensitized or polysensitized.

Environmental factors in epithelial barrier dysfunction.

The main interfaces controlling and attempting to homeostatically balance communications between the host and the environment are the epithelial barriers of the skin, gastrointestinal system, and airways. The epithelial barrier constitutes the first line of physical, chemical, and immunologic defenses and provides a protective wall against environmental factors. Following the industrial revolution in the 19th century, urbanization and socioeconomic development have led to an increase in energy consumption, and waste discharge, leading to increased exposure to air pollution and chemical hazards. Particularly after the 1960s, biological and chemical insults from the surrounding environment-the exposome-have been disrupting the physical integrity of the barrier by degrading the intercellular barrier proteins at tight and adherens junctions, triggering epithelial alarmin cytokine responses such as IL-25, IL-33, and thymic stromal lymphopoietin, and increasing the epithelial barrier permeability. A typical type 2 immune response develops in affected organs in asthma, rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, food allergy, and atopic dermatitis. The aim of this article was to discuss the effects of environmental factors such as protease enzymes of allergens, detergents, tobacco, ozone, particulate matter, diesel exhaust, nanoparticles, and microplastic on the integrity of the epithelial barriers in the context of epithelial barrier hypothesis.

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). PURPOSE: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. RESULTS: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. CONCLUSION: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

Omalizumab in non-allergic Asthma: A report of 13 cases.

BACKGROUND: There are limited data regarding the effectiveness of omalizumab in patients with non-allergic asthma. OBJECTIVE: To evaluate the clinical and functional effectiveness of omalizumab in patients with non-allergic asthma. METHODS: The study was a single-center, retrospective chart review of patients with non-allergic asthma who were treated with add-on omalizumab between February 2014 and March 2016. After omalizumab was started, data of the asthma control test (ACT), pulmonary function test, and daily oral corticosteroid (OCS) dosage were collected at baseline, 16 weeks, 1 year, 2 and 3 years (if available). The number of exacerbations/hospitalizations were collected 1 year prior to and 6 months/1 year after omalizumab. To calculate the total daily dosage of OCS in milligrams, data for 6 months/1 year prior and after omalizumab treatment were recorded. RESULTS: Thirteen patients were included. After omalizumab, the mean ACT was significantly increased at 16 weeks (n = 13, p = 0.002), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.006). The mean daily OCS dose was significantly decreased at 16 weeks (n = 13, p = 0.001), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.04). The mean number of exacerbations and hospitalizations were decreased at the 6th month (n = 13; p = 0.001, p = 0.005) and 1st year (n = 7; p = 0.01, p = 0.02). The mean total quantity of OCS decreased 42% from 1.4 to 0.8 g in the six-month period prior to and post-omalizumab treatment (n = 6, p = 0.02) and decreased 76% from 3.8 to 0.9 g at 1 year in the pre vs. post-omalizumab treatment comparison (n = 7, p = 0.01). Six (46.2%) patients responded perfectly and seven (53.8%) partially responded to treatment. CONCLUSION: Omalizumab can be effective in non-atopic severe asthma.

[Relation of systemic comorbidities in asthma with disease: control, severity and phenotype]. / Astimda sistemik komorbiditeler: Kontrol, agirlik ve fenotip ile iliskisi.

INTRODUCTION: Asthma is a heterogeneous and chronic inflamatory disease that can accompany many comorbidities during the course. It is thought that different comorbidities are seen in different phenotypes of asthma. Our aim is to establish the relationship between systemic comorbidities seen in asthmatic patients and asthma control, severity and phenotypes. MATERIALS AND METHODS: Patients who were followed up with asthma diagnosis in Polyclinics of Ankara University Faculty of Medicine Department of Immunology and Allergy Diseases were questioned about demographic characteristics. Their control status and disease severity were determined. They were classified whether r atopic, eosinophilic or obese. Systemic comorbidities were questioned and Charlson comorbidity indices (CCI) were calculated. The difference between the groups in the terms of CCI was evaluated. RESULT: Two hundred and twenty-nine patients (29E/200K, 12.7%/87.3%) with a mean age of 51.25 ± 12.02 were included in the study. CCI was significantly higher in patients without asthma control than in those with partial control and well control (CCI: 2.22, 1.69, 1.50, respectively) (p= 0.03). There was also a linear correlation between asthma severity and CCI (CC: 0.22, p= 0.001). Allergic comorbidities were more frequent in the eosinophilic phenotype (p= 0.01) (OR: 2.20, 95% CI: 1.2-3.8) but did not increase the likelihood of accompanying systemic comorbidity (OR: 1.05, 95% CI: 0.8-1.2) (p> 0.05). The likelihood of systemic comorbidity, especially HT, coroner artery diseases, depression, was higher in nonatopics than in atopic patients (OR: 2.039 95% CI: 1.04.11) (p= 0.03). Obesity was found to be a risk factor for systemic comorbidities (OR: 1.36 %95 C1: 1.09-1.84) (p= 0.04). CONCLUSIONS: Severe, uncontrolled, obese or nonatopic asthma patients should be examined for systemic comorbidities. There is a need for further study to assess the relationship between treatment of established comorbidities and asthma course.

Smoking attitudes of the patients with allergic rhinitis: a comparison with asthma and chronic obstructive pulmonary disease. Are there differences when only upper airways are involved?

INTRODUCTION: Despite the well documented relationship between lower airway diseases and smoking, there are limited data about smoking and allergic rhinitis (AR). In this study, we aimed to document the smoking behaviour and environmental tobacco smoke (ETS) exposure of the patients with AR in comparison with patients with asthma, chronic obstructive pulmonary diseases (COPD) and healthy controls (HC). MATERIALS AND METHODS: Demographics and disease characteristics were recorded from case files whereas smoking history, childhood and current exposures to ETS, as well as the smoking behaviors were investigated by a self reported questionnaire. RESULT: A total of 937 subjects comprising patients with AR (n= 252), asthma (n= 249), COPD (n= 188) and HCs (n= 248) were enrolled in the study. The rates of active smokers were 35% (HCs), 26% (COPD), 21% (AR), and 11% (asthma). Exposure to ETS while with friends was significantly higher among HCs and AR groups (p< 0.0001). The rate of willingness to quit smoking is high in AR patients (73%) but they did not determined about date of quiting. CONCLUSIONS: Our results showed that a significant number of patients with AR actively smoke and neither the patients with AR nor the people in their surroundings were sufficiently aware of the health hazards of smoking with AR. It seems necessary to inform patients with about the health effects of smoking on all respiratory tract diseases.

Does the medical diagnosis of occupational asthma coincide with the legal diagnosis?

OBJECTIVE: The incidence of occupational asthma (OA) is increasing worldwide. In this study, we first aimed to document the rate of diagnosis of OA among patients who were referred to our clinic from the Social Security Institution and the factors that affected diagnosis; secondly, we aimed to assess the consistency of the medical and legal diagnoses. METHODS: The study involved 132 consecutive patients who were referred to our clinic for the evaluation of OA between 2010 and 2015. Detailed workplace history, the tools used in the diagnosis such as peak expiratory flow (PEF) monitoring and bronchial provocation tests, and the final medical diagnosis were recorded from case files. RESULTS: Asthma was diagnosed in 75% (n = 99) of the patients. Among them, 22.2% were diagnosed as having OA. The diagnosis was confirmed by serial PEF measurements, non-specific bronchial hyperreactivity assessment or both of the tests both at work and off-work periods. OA diagnosis was mostly established in active workers (72.7%). The legal diagnosis period was completed in 54.5% of these 22 patients, and 50% (n = 11) were officially diagnosed as having OA with a 91.6% concordance with medical diagnosis. CONCLUSION: This study verifies the importance of diagnosing asthma correctly as a first step in the evaluation of OA. Diagnostic tests other than specific provocation tests could be preferential in patients who still work in the same field. We believe that cooperation with the patient's occupational physician and adequate recognition of the work environment will improve the consistency of legal and medical diagnoses.

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. RESULTS: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. CONCLUSION: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.

Obesity-asthma phenotype: Effect of weight gain on asthma control in adults.

INTRODUCTION: The obesity-asthma phenotype has become an increasingly common situation in our clinical practice. The mechanisms behind poor asthma control in subjects who are obese remain unclear. We aimed to determine the effect of obesity on asthma control in a group of adult patients Method: Subjects who had been diagnosed as having asthma and who were admitted to our clinic were included to this study. Body mass index (BMI) and asthma control status of the patients were evaluated. BMI values at the time of diagnosis were also collected from the patient files, and the difference between basal and current BMI values were calculated. The effect of obesity and weight gain on asthma control was investigated. RESULTS: The study population was composed of 218 patients (29 men, 189 women), with a mean (standard deviation) age of 52.01 ± 11.6 years. Fifty-four percent of the patients were obese, 27.5% were overweight, and 18.3% were of normal weight. The baseline and current BMI values were higher in women than in the men. BMI increased with the increase in age or disease duration. Asthma control was poor in the patients who were obese and overweight despite optimal treatment. Moreover, asthma control was worse in patients who gained weight during the follow-up period. CONCLUSION: In our study, we found a significant relationship between obesity and asthma control. In addition, weight gain and being nonatopic also was found to worsen asthma control. In light of our finding that weight gain led to a decrease in asthma control, we suggest that weight loss may improve the course of asthma.

[Attitudes of adult asthma patients towards influenza vaccination]. / Eriskin astimli hastanin influenza asisina yaklasimi farkli mi?

INTRODUCTION: It is known that viral infections trigger exacerbations in asthma patients.There are conflicting reports on whether influenza vaccine is preventive or not. In this study, we aimed to evaluate asthmatic patient's attitude towards influenza vaccine and to determine which factors affect this attitude. MATERIALS AND METHODS: A questionnaire involving data about demographic information, co-morbidities, frequency of viral upper respiratory tract infections, subject's influenza vaccination status and attitude towards vaccination had been filled for our outpatient clinic asthma patients and also for healthy controls. Results were evaluated separately for the two groups and then compared to each other. RESULT: For the study; 108 asthma patients (91 female, 17 male) and 110 non-asthmatic controls (64 female, 46 male) were enrolled. In asthma group, vaccination rates were significantly higher in the previous year (40.7%) and nearly half of them stated that they do regularly have influenza shots every year. Contrast to this find; half of the patients in the control group stated that they do not need to vaccinate themselves and 26.2% said that they don't believe influenza vaccine has any preventive effect. Also in the asthma group, this ratio was similar to the control group (20.3%). In asthma group, 66.7% of the patients who had side effects at their previous shots did not want to vaccinate themselves this year (p= 0.02). More than a half of the patients (53.1%) whom did not have shots had an episode of viral upper respiratory tract infection this year and this rate was significantly lower in the vaccinated group (p= 0.00). This result highlights the preventive effect of vaccination. CONCLUSIONS: We found that asthma patients' knowledge on influenza infection and vaccine were insufficient and also their belief towards the preventive features of the vaccination was low. Informing and encouraging patients about preventive medicine through various activities and meetings would be crucial.

[The profile of severe asthmatics: Results from a specialized asthma clinic]. / Özellesmis bir astim polikliniginin agir astim verileri.

Introduction: In patients with severe asthma, individualized treatment, and appropriate phenotyping are required to achieve control. In our study, our aim was to examine the characteristics of a specific patient group in a specialized tertiary asthma outpatient clinic, which is the primary setting for evaluating severe asthma patients, with the intention of obtaining national data. Materials and Methods: In this cross-sectional observational study, sociodemographic, clinical presentations, laboratory results, and spirometry measurements of patients with severe asthma who were followed up in our specialized asthma outpatient clinic for at least one year were recorded. Patients were defined as eosinophilic if they had a blood eosinophil count of 300/µL or higher at least twice during the oral corticosteroid free-period or 150/µL or higher under oral corticosteroids as allergic if they had sensitization to at least one inhalant allergen consistent with their history. Result: Overall, 201 severe asthma patients (74.1% female) with a median disease duration of 15 (min-max= 1-49) years and a median follow-up duration of 7 (min-max= 1-40) years were analyzed. Most of the patients (56.7%) had adult-onset asthma [median age of onset was 32 (min-max= 10-62) years]. Overweight and obese patients were in the majority (31.8%, and 41.8%, respectively) and the median body mass index was 29 (min-max= 17.5-49.5). More than half of the patients (55.2%) had controlled asthma and the median Asthma Control Test score at the last visit was 23. Biologic therapies were applied to 73.1% (n= 147) of the patients [60.5% (n= 89) omalizumab, 39.5% (n= 58) mepolizumab]. Half of the group was allergic (49.3%) and three-quarters of them were eosinophilic (72.1%). Allergic patients had earlier asthma onset and had more controlled disease than nonallergic ones. Eosinophilic patients were younger and less obese than noneosinophilic patients. Obese and late-onset asthmatics had more uncontrolled disease than normal weight subjects and early onset patients. Conclusions: The high rate of disease control in the patients with severe asthma in the current study demonstrated the importance of targeted individualized therapy with accurate phenotyping in specialized asthma outpatient clinics.

[Biologics for the treatment of severe asthma: Current status report 2023]. / Agir astim tedavisinde biyolojikler: Güncel durum raporu 2023.

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis.

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem. Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis. Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results. Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues. Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Evaluation of the functional parameters in scleroderma cases with pulmonary involvement.

To evaluate the relationship between functional changes in the scleroderma patients with pulmonary involvement and the diagnostic tests and to identify the tests that may be helpful in early diagnosis. In this prospective study, 33 scleroderma patients with pulmonary involvement were included. Pulmonary function tests, echocardiography, arterial blood gases, six minute walk tests, thorax high resolution computed tomography were performed and all patients were classified according to MRC dyspnea scores and NYHA(WHO) functional classification. Patients were also asked to conclude Saints Georges Respiratory Questionnaire (SGRQ). DLCO% found to be the earliest deteriorated parameter in our patients. Sensitivity of FVC%/DLCO% ratio, for detecting pulmonary arterial hypertension as a noninvasive method, was found low. SGRQ was found to be correlated with all functional parameters used in scleroderma follow up. Patients with scleroderma should be evaluated for pulmonary involvement and must be followed up ever if they were asymptomatic. Pulmonary function tests, echocardiography, thorax high resolution computed tomography, six minute walk tests are valuable tools that should be used in diagnosis and follow up. NYHA (WHO) functional classification, MRC and Borg dyspnea scores are also helpful for early diagnosis. SGRQ can also be helpful to evaluate the patients functional capacity in diagnosis and follow up as a non invasive parameter.