Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

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.

Clinical features and immunoglobulin replacement therapy outcomes of adults with common variable immunodeficiency: a single centre experience

Background/aim: Common variable immunodeficiency (CVID) characterized by defective immunoglobulin production is the most prevalent form of symptomatic primary immunodeficiency (PID) in adults. We aimed to reveal the clinical features of adults with CVID and to evaluate the effects of immunoglobulin replacement treatment (IRT) on hemato-immunological findings. Materials and methods: This study included 26 adult patients receiving IRT. Two measurements of complete blood counts and major immunoglobulin levels obtained at the beginning-end of follow up period were used for comparisons. Lymphocyte subsets and B-cell subgroups were measured only at the time of presentation. Results: The most common complications were related to respiratory and digestive systems and organomegaly. Chronic diarrhoea and low body weight were positively correlated with the percentage of CD8+ T cells (p = 0.019 and p = 0.003, respectively) but negatively correlated with the CD4/CD8 ratio and the percentage of CD19+ B cells (p = 0.019 and p = 0.005 for both parameters, respectively). At the end of period, the distribution of haematological parameters significantly improved, and immunoglobulin M (IgM) level increased to detectable levels (p = 0.035). Conclusions: There are apparent relationships among chronic diarrhoea and low body weight, and deterioration of T and B cell immunity in adults with CVID. IRT improves the whole blood parameters and stimulates immunoglobulin M (IgM) production. The later effect supports the immunomodulatory feature of this therapy.

Evaluation of anxiety levels and factors associated with positive test results in patients with drug hypersensitivity.

BACKGROUND: High anxiety has been reported in patients with drug hypersensitivity reaction (DHR); however, its relationship with the test results was not studied previously. OBJECTIVE: We aimed to investigate the association of patient anxiety with the results of drug tests together with the other contributing factors. METHODS: Sixty-seven patients were included in the study between November 2012 and April 2013, in whom drug tests were performed after clinical evaluation and application of the Penn State Worry Questionnaire (PSWQ). RESULTS: The mean ± standard deviation (SD) age was 43.5 ± 12.9 years, and 73.1% of the patients were females. The patient group had significantly higher mean ± SD PSWQ score than 35 control subjects without histories of DHRs and major psychiatric disorders (47.95 ± 14.64 versus 40.22 ± 11.86, p = 0.008). However, the mean ± SD. PSWQ score of the patients with positive drug test results was not significantly different from the patients with negative drug test results (46.06 ± 13.41 versus 50.47 ± 18.02, p = 0.32). Panic attack symptoms were more common in the reactions with positive test results than in the reactions with negative test results (74.0% versus 48.9%, p = 0.01). However, presence of panic attack symptoms [odds ratio (OR): 1.25, 95% confidence interval (CI): 0.44-3.54; p = 0.67] was not found independently associated with positive test results in the multiple logistic regression model. CONCLUSION: Patients with DHR have high levels of anxiety; however, this is not related to the results of drug tests. Because panic reaction symptoms may accompany the objective symptoms of DHR, a complete clinical work-up is required before deciding whether the reaction is related to panic or a "true DHR."

Relationship between asthma and IL-17 gene polymorphism in a Turkish population.

BACKGROUND: Asthma is a prevalent chronic obstructive disease of the airways. AIMS: The aim of our study was to investigate the relationship between asthma and IL-17F gene 74488 T > C, IL-17A gene -197G > A, and IL17A gene -737C > T polymorphisms in Turkish population. METHODS: In our study, peripheral blood samples collected from a total of 127 subjects, with 65 in the patient group and 62 in the control group, were analyzed for IL-17F gene 74488 T > C, IL-17A gene -197G > A, and IL17A gene -737C > T polymorphisms using next-generation sequencing. RESULTS: There was no statistically significant relationship between IL-17A gene -197G > A and IL-17A gene -737C > T polymorphisms and the risk of developing asthma. It was found that the risk of developing asthma was 2.9-fold higher in individuals with a C allele in the IL-17F gene 7488 T > C polymorphic site than the individuals with a T allele. It was shown that ATT and GCT haplotype carriers had a greater disease risk compared with the GTT haplotype carriers. CONCLUSIONS: In conclusion, IL-17F gene 7488 T > C polymorphism was found to be associated with asthma in the Turkish population. The IL-17 gene should be further investigated as a potential candidate gene in predicting asthma susceptibility and in the treatment of asthma.

Efficacy of abatacept treatment in a patient with enteropathy carrying a variant of unsignificance in CTLA4 gene: A case report.

BACKGROUND: Cytotoxic T Lymphocyte Antigen-4 (CTLA4) deficiency is a genetic defect that causes a common variable immunodeficiency (CVID) clinical phenotype. Several studies have reported an association between CTLA mutations or variants and various autoimmune diseases. Targeted therapy models, which have become increasingly popular in recent years, have been successful in treating CTLA4 deficiency. In this article, we discuss the clinical outcomes of abatacept treatment in a patient with CTLA4 and lipopolysaccharide-responsive beige-like anchor (LRBA) variants that was previously diagnosed with CVID. CASE SUMMARY: A 25-year-old female patient, who was visibly cachectic, visited our clinic over the course of five years, complaining of diarrhea. The patient was diagnosed with ulcerative colitis in the centers she had visited previously, and various treatments were administered; however, clinical improvement could not be achieved. Severe hypokalemia was detected during an examination. Her serum immunoglobulin levels, CD19+ B-cell percentage, and CD4/CD8 ratio were low. An endoscopic examination revealed erosive gastritis, nodular duodenitis, and pancolitis. Histopathological findings supported the presence of immune mediated enteropathy. When the patient was examined carefully, she was diagnosed with CVID, and intravenous immunoglobulin treatment was initiated. Peroral and rectal therapeutic drugs including steroid therapy episodes were administered to treat the immune mediated enteropathy. Strict follow-ups and treatment were performed due to the hypokalemia. After conducting genetic analyses, the CTLA4 and LRBA variants were identified and abatacept treatment was initiated. With targeted therapy, the patient's clinical and laboratory findings rapidly regressed, and there was an increase in weight. CONCLUSION: The heterozygous CTLA4 variant identified in the patient has been previously shown to be associated with various autoimmune diseases. The successful clinical outcome of abatacept treatment in this patient supports the idea that this variant plays a role in the immunopathogenesis of the disease. In the presence of severe disease, abatacept therapy should be considered until further testing can be conducted.

A Case of Common Variable Immunodeficiency with CREBP Gene Mutation without Rubinstein Taybi Syndrome Features.

Hypogammaglobulinemias, based on inborn errors of immunity, are primary immunodeficiencies (PIDs) that can also be diagnosed for the first time in adulthood. Common variable immunodeficiency (CVID) is a multifactorial disease often symptomatic due to antibody deficiency. In addition, some PIDs are classified into the category of immunodeficiencies with syndromic features due to their accompanying clinical findings unrelated to immunity. In this article, a patient with CVID who was diagnosed in adulthood and who was revealed to have a mutation specific to Rubinstein-Taybi syndrome and clinical features reminiscent of this syndrome only after molecular tests was presented.

Role of systemic immune-inflammation index in asthma and NSAID-exacerbated respiratory disease.

OBJECTIVE: Asthma is a heterogeneous disease characterized by chronic progressive airway inflammation. Although the disease has numerous phenotypes, there are no practical biomarkers for distinguishing the phenotypes from one another. To address this challenge, we aimed to reveal whether the systemic immune-inflammation index (SII), an important indicator of systemic inflammation and prognosis in various malignancies and vasculitis, can be used for distinguishing between asthma and NSAID-exacerbated respiratory disease (NERD). METHODS: The study enrolled 105 patients (asthma: n = 69; NERD: n = 36). SII was calculated using the formula of neutrophil X platelet/lymphocyte number. Major risk factors, namely ACT score, eosinophil level, total IgE level, N-L ratio (NLR), P-L ratio (PLR), and SII, were evaluated by logistic regression analysis. RESULTS: No significant differences were found between the clinical features of the two study groups. Patients with an SII value ≥895.6 had a probability of having NERD with a sensitivity of 30.56%, whereas those with a lower SII had a probability of having asthma with a sensitivity of 92.65%. In the logistic regression analysis, no risk factor was determined for identifying asthma or NERD. The N-L ratio was found to be the risk factor affecting categorized SII (OR = 264.2, 95% CI 9.9-7046.5, P = 0.001). CONCLUSION: This is the first study to evaluate SII as a tool for differentiating asthma phenotypes. The presence of SII below the cutoff value can help exclude the diagnosis of NERD. There is a need for large-scale prospective studies to compare different phenotypes and determine the optimal cutoff value.

Evaluating nonadherence to preventer inhaler therapy in severe asthmatic patients receiving omalizumab.

BACKGROUND: Asthma is one of the most common chronic diseases worldwide and can often be controlled by existing treatments, but in the 5%-10% of patients with severe asthma, control is frequently more challenging. The aim of this paper is to evaluate the adherence to preventer inhaler therapy in severe asthmatic patients receiving omalizumab, a recombinant humanized monoclonal anti-IgE antibody indicated for moderate-to-severe asthma. METHODS: This study included 29 patients who were receiving omalizumab treatment as maintenance therapy. All patients completed the six question Turkish Modified Morisky Scale. In addition, patients were classified by adherence to their prescribed preventer therapy, based on pharmaceutical and medical device institution records from the preceding one year. RESULTS: Of the 29 enrolled patients, 24.1% had NSAID-exacerbated respiratory disease; 75.9% were female and median age was 47.2 ± 12.99 years. Severe asthma patients demonstrated high levels of motivation (98.8%, n = 28) and knowledge (86.2%, n = 22) about asthma treatment. Nevertheless, the rate of nonadherence to preventer inhaler therapy was only 34.5% (n = 10). There were no significant differences among the characteristics of the patients that might affect the adherence to inhaler therapy. CONCLUSION: In patients with severe asthma, suboptimal adherence to preventer inhaler therapy is common before and after omalizumab treatment. Although patients have high levels of motivation and knowledge about asthma treatment, adherence to inhaler preventer therapy declined after omalizumab therapy. Given these findings, it is important to decide whether preventer inhaler therapy should be continued as monotherapy or be discontinued inpatients exhibiting impaired adherence to biological agents, such as omalizumab.

Is the Perioperative Period No Longer a Problem for Adult Asthmatics under Control?-OPERA Study.

OBJECTIVES: Asthma is a global problem and chronic condition that persists through patient's entire life, during which the possibility of a surgical procedure is common. An accurate clinical and functional evaluation of respiratory functions and asthma control is needed in patients undergoing surgical procedures and requiring general anesthesia. The aim of this study was to disclose any possible relation between postoperative complications and some pre- and postoperative factors. MATERIALS AND METHODS: In this prospective cross-sectional study, randomly selected 111 asthmatic patients who presented to 10 different tertiary centers were included. The patients were evaluated at three different periods; any day between 1-7 days before surgery, and postoperative third and seventh to tenth days. RESULTS: Among the patients included in the study, 86 (77.5%) were women and mean age was 52.2±13.8 years. General anesthesia was the most common anesthesia type (89.2%), and 33.3% of patients had had a thoracoabdominal surgery. There was a statistically significant difference between pre- and postoperative third-day values, including ACT scores (22.2±3.16 and 21.59±3.84, respectively; p<0.001); forced expiratory volume during the first second (84.92±19.12 and 78.26±18.47, respectively; p<0.001); peak flow rate (79.51±21.12 and 70.01±19.72, respectively; p<0.001); and SaO2 (96.95±1.82 and 95.8±3.32, respectively; p<0.001). Bronchospasm and pain were the most common complications during the postoperative period. CONCLUSION: Controlled asthma under treatment steps 1-2-3 does not cause any serious postoperative pulmonary complications (PPCs). Therefore, achieving an optimal control level of asthma during the preoperative period must be considered the "gold standard" to reduce the risk of PPCs in asthmatic patients.

The Frequency and Risk Factors for Oropharyngeal Candidiasis in Adult Asthma Patients Using Inhaled Corticosteroids.

OBJECTIVES: Worldwide, asthma is a major health problem and inhaled corticosteroids (ICS) are the mainstay of asthma treatment. High-dose and long-term use of ICS can result in some side effects. The present study aimed to determine the frequency of oral and systemic candidiasis infections in adult asthma patients using ICS, and to identify possible risk factors. MATERIAL AND METHODS: This study included 186 randomly selected adult asthma patients that presented to allergy clinic between May 2011 and September 2012. RESULTS: Among the patients, 147 (79%) were female. The lifelong incidence of oral candidiasis was 19.4% (n=36), whereas 5.38% (n=10) of the patients already had it by the time of the study. The lifelong incidence of any fungal infection was 59.7% (n=111). There weren't any significant differences in gender, age, age at onset of asthma, oral hygiene, atopy, or comorbid diseases between the oropharyngeal candidiasis (OPC)-positive and -negative groups. A history of persistent rhinitis, use of a leukotriene receptor antagonist together with ICS, and use of ciclesonide as an ICS were associated with a higher incidence of OPC. CONCLUSION: In the present study the incidence of OPC in adult asthma patients was quite high, but no definitive risk factors were identified. Further studies are needed to distinguish these individual differences.