Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Drug Allergy in Children: Adverse Reactions after Skin Testing.

INTRODUCTION: Skin tests are one of the most widely used diagnostic tools for suspected drug allergies in children. Studies on systemic reactions occurring during skin testing with allergens have mostly been conducted in pediatric and adult patient groups together. However, data on adverse reactions including allergic reactions after drug skin tests in children are scarce. It is aimed to determine the adverse reactions after skin test in children with suspected drug allergy. METHODS: Patients who underwent a drug skin test due to the suspicion of drug allergy between May 2017 and June 2020 were evaluated, retrospectively. Data about adverse reactions seen after skin testing at the testing area in the clinic were analyzed. RESULTS: The study included 1,073 children (585 [54.5%] boys and 488 [45.5%] girls) with a median age of 7.5 years. A total of 12 (1.1%) reactions were detected after skin testing, and 4 (0.4%) of them were allergic reactions. Of the allergic reactions, three were anaphylaxis and one was urticaria. Two of the reactions (1 anaphylaxis and 1 urticaria) were detected after the skin prick test and the remaining 2 were detected after intradermal test. Three of the nonallergic reactions were considered as vasovagal reactions and seven were considered as nonspecific and anxiety-related reactions. CONCLUSION: Although drug skin tests were generally well-tolerated and adverse reactions were rare, severe allergic reactions including anaphylaxis may ensue. Skin tests should be necessarily performed in clinical settings in experienced centers.

Evaluation of the triggers and the treatment models of anaphylaxis in pediatric patients.

OBJECTIVE: Anaphylaxis is an acute, life-threatening systemic hypersensitivity reaction. We aimed to evaluate the demographic and clinical characteristics of patients presenting with anaphylaxis, as well as triggers and risk factors, and to determine the rate of adrenaline auto-injector (AAI) usage. METHODS: The study was planned in the pediatric allergy outpatient clinic over a 1-year period. The data of children diagnosed with anaphylaxis were evaluated retrospectively; demographic characteristics, causes of anaphylaxis, and treatment modalities were recorded in the created study form. RESULTS: Eighty children (29 females) with a median age of 6.5 years (range: 1 month-17 years) were evaluated. The most common triggers were foods under 2 years of age (73%), and drugs (70%) above 2 years of age. Nearly half of the anaphylaxis episodes (n=41, 51.3%) occurred at home. Cutaneous and respiratory symptoms were the most commonly reported complaints (98.8%). The median age of the patients at the first attack with severe anaphylaxis (n=29, 36.3%) was significantly higher than the rest (p:0.007). The age at onset of the reaction (p:0.006) and occurrence of the reaction in hospital conditions (p<0.001) were determined to be significant risk factors for severe anaphylaxis. Most of them received antihistamines (95.7%) and corticosteroids (91.3%), while 78.3% received adrenaline. Only 9.5% of patients with recurrent episodes of anaphylaxis used AAIs. CONCLUSION: Foods in infants and drugs in older children were the leading causative allergens of anaphylaxis. The most common clinical manifestations were respiratory and cutaneous symptoms. The older age at onset of the reaction and the occurrence of the reaction in hospital conditions were determined to be significant risk factors for severe anaphylaxis. It was determined that the frequency of AAI use was low among patients and their families.

Risk Factors of Challenge-Proven Beta-Lactam Allergy in Children with Immediate and Non-Immediate Mild Cutaneous Reactions.

INTRODUCTION: Beta-lactam (BL) antibiotics are the most often involved drugs in allergic reactions. Mild cutaneous reactions such as maculopapular exanthema or urticaria are the most common presenting complaints of BL allergy in the pediatric population. However, it can be challenging to distinguish BL-induced allergy from reactions due to infections or other reasons. In this study, we aimed to determine the clinical characteristics and potential risk factors of true BL allergy in children with suspected mild cutaneous reactions to BLs. METHODS: We evaluated children who were admitted to our pediatric allergy clinic with suspected BL allergy in between January 2015 and March 2020. Patients with a history suggestive of immediate and non-immediate mild cutaneous reactions were included in the study. The oral challenge test (OCT) with the culprit drug was performed on all patients to confirm the diagnosis. RESULTS: Two hundred fourteen (119 male and 95 female) patients with a median age of 4.9 years were evaluated. BL allergy was confirmed in 10.7% (23) of the patients, according to the OCT results. Most of the proven allergic reactions were of the immediate type (73.9%), and urticaria was the most common presenting complaint (60.8%) in proven BL-allergic patients. The negative predictive value of penicillin-G skin testing was 89.7% for immediate-type penicillin allergy and 93.4% for non-immediate reactions. Also, positive predictive value of penicillin-G skin testing was 50% for immediate and 25% for non-immediate reactions. In the multivariate logistic regression analysis, a history of proven drug allergy (Exp (B): 7.76, 95% CI: 1.88-31.97, p = 0.005) was found to be the risk for BL allergy. CONCLUSION: This study highlighted that OCTs should be performed to confirm the diagnosis in patients suspected of immediate and non-immediate mild cutaneous reactions to BLs and remove the overestimated "BL allergy" label. In these patients, a history of proven drug allergy might be a risk factor for true BL allergy.

Hypersensitivity to Ibuprofen: Real-Life Experience in Children with History of Suspected Immediate Reactions.

INTRODUCTION: Ibuprofen is the most common culprit drug causing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children. We aimed to evaluate the frequency, clinical characteristics, and risk factors of confirmed ibuprofen allergy in children presenting with a history of suspected immediate type ibuprofen-induced hypersensitivity reactions. METHODS: We evaluated 50 (35 M, 15 F) children with a median age of 7 years, who were referred to our clinic with suspected immediate ibuprofen hypersensitivity. Patients were subjected to a diagnostic work up including drug provocation tests (DPTs) with the culprit drug. Reactions were classified according to the European Academy of Allergy and Clinical Immunology Task Force recommendations for pediatric patients. Proven ibuprofen allergic patients underwent DPT to find a safe alternative drug. RESULTS: Ibuprofen allergy was confirmed in 34% (n: 17) of children; 9 patients were diagnosed by DPTs and 8 patients diagnosed based on their histories. Angioedema was the most common clinical manifestation (n: 30, 60%). Among patients with proven ibuprofen allergy, 7 of them were classified as cross-intolerant. Cross-intolerance reactions were further classified as NSAID-exacerbated cutaneous disease (n = 1) and NSAID-induced urticaria/angioedema/anaphylaxis (n = 6). As an alternative drug, paracetamol was safely tolerated, whereas 1 patient developed angioedema and urticaria with nimesulide. Older age and male gender were identified as independent risk factors for immediate-type ibuprofen allergy. CONCLUSION: DPTs should be performed to confirm or exclude ibuprofen allergy in children and to find safe alternative drugs. Male gender and older age are risk factors for ibuprofen allergy. NSAID-induced hypersensitivity reactions in the pediatric population cannot be well defined using the adult classification system.

Antibiotic allergy in children with cystic fibrosis: A retrospective case-control study.

Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF). AIM: To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF. METHODS: In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression. RESULTS: ß-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-ß-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed ß-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity. CONCLUSION: Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.

Risk Factors for Immediate-Type Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: A Retrospective Case-Control Study.

Background: Local anesthetics (LA) are relatively safe and rarely cause immediate hypersensitivity reactions. The data on immediate LA hypersensitivity and its risk factors in children are limited. Aim: To evaluate risk factors of immediate LA hypersensitivity. Methods: The retrospective case-controlled study included 17 patients with confirmed immediate LA hypersensitivity. For each patient, three age- and gender-matched control subjects were included in the study. LA hypersensitivity was excluded by skin tests and subcutaneous drug provocation tests in all control subjects. Results: The most common allergic assessment in the patient/control group was for lidocaine (n=5; 29.4%, vs n=23; 45.1%). Suspected LA hypersensitivity reactions were found to be associated with cutaneous manifestations in 14 (82.4%) patients and in 7 (13.7%) of the controls. A history of exposure to local anesthetics twice or more was present in 11 (64.7%) patients vs 6 (11.8%) controls. In conditional regression analysis, repeated LA exposure (≥2) and cutaneous findings were determined as significant risk factors (Odds Ratio [OR]:5.7; 95% Confidence Interval [CI]:1.2-27.1; P=0.029 and (OR:17.3; 95% CI:3.6-82.5; P<0.001, respectively). Conclusion: Cutaneous manifestations and a history of LA exposure twice or more were predictive factors for LA allergy confirmed by skin test in children.

Evaluation of Suspected Macrolide Allergies in Children.

OBJECTIVE: Macrolides are often accepted as safe antibiotics due to their low allergenicity. However, studies on macrolides, particularly studies evaluating cross-reactivity in macrolides, are highly rare in children. This study aimed to evaluate the clinical manifestations, confirmation rate, and frequency of cross-reactivity in children admitted with suspicious clarithromycin or azithromycin allergy. MATERIALS AND METHODS: A total of 61 children suspected of macrolide antibiotic allergy (clarithromycin, n = 39 and azithromycin, n = 22) were evaluated. Allergy work-up including drug provocation tests were performed in all patients to confirm drug allergy. RESULTS: Macrolide allergy was confirmed in 9.8% (n = 6) of patients (azithromycin, 18.2% [n = 4] and clarithromycin, 5.1% [n = 2]). There was no significant difference between the confirmation rate of clarithromycin and azithromycin (P = .117). Cross-reaction with clarithromycin was confirmed in 2 (33.3%) patients with azithromycin allergy. CONCLUSION: Drug skin tests are not capable of confirming or ruling out macrolide allergy, and oral provocation tests are essential for a definitive diagnosis. Cross-reactivity, albeit rare, can occur between clarithromycin and azithromycin, which are the most frequently used macrolides in children.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Risk Factors for the Development of IgE-Mediated Food Allergy in Preschool Children with Asthma.

BACKGROUND: Food allergy is a component of the atopic march and may have effects on asthma. This study aimed to evaluate the risk factors for confirmed immunoglobulin E-mediated food allergies and their impact on the clinical picture in preschool children with asthma. METHODS: Clinical history and allergic assessment results were obtained from medical records and analyzed retrospectively. Preschool children with asthma were included in the study and the characteristics of food allergy and asthma were evaluated. The patients were grouped as those with food allergy (Group I, n = 60) and those without (Group II, n = 98). RESULTS: In patients with food allergy and asthma, the number of episodes requiring systemic steroids in the last year (p = 0.002), atopic dermatitis (p = 0.001), parental atopic disease (p = 0.009) and aeroallergen sensitivity rates (p < 0.001) was higher than patients without food allergies. The use of medium or high doses of inhaled steroids to achieve asthma control was more frequent in patients with food allergies (p = 0.014). Parental history of atopic disease [p = 0.007, odds ratio (OR): 3.27, 95% confidence interval (CI) 1.37-7.77)], atopic dermatitis (p = 0.017, OR: 2.80, 95% CI: 1.19-6.57), starting complementary food after 6 months (p = 0.004, OR: 3.9, 95% CI: 1.5-10.0) and having aeroallergen sensitivity (p < 0.001, OR: 6.01, 95% CI: 2.21-16.29) were identified as significant risk factors for food allergy. CONCLUSION: Asthmatic preschool children with food allergies are more likely to have a parental atopic disease, atopic dermatitis, aeroallergen sensitivity and starting complementary food after 6 months. These patients experience more asthma attacks and need higher doses of steroids.

Food allergy and asthma in preschool children affect each other mutually. Food allergy is a component of the atopic march, a risk factor for the development of asthma, and is also included in the modified asthma predictive index in children with wheezing. Therefore, the manifestation of asthma-related symptoms such as cough and wheezing along with food allergy in this age group may facilitate the decision to start asthma control therapy. On the other hand, having asthma is a risk factor for food-related reactions to be more serious. In the current study, we compared patients with and without food allergies. We determined that other atopic diseases (allergic rhinitis and atopic dermatitis) are more common in children with food allergies, and asthma control can be achieved with higher inhaler steroid doses.

Risk Stratification as a Predictive Factor for Cephalosporin Allergy: A Case-Controlled Study.

BACKGROUND: Compared to penicillin, cephalosporin allergies are less common in children, and their diagnostic approach is less standardized. A recent European Academy of Allergy and Clinical Immunology position paper provided a risk stratification system for patients with suspected ß-lactam hypersensitivity reactions. OBJECTIVE: This study aimed to evaluate risk stratification and predicting factors for confirmed cephalosporin hypersensitivity. METHODS: The case-controlled study included patients with confirmed cephalosporin hypersensitivity (skin tests, n = 53; drug provocation, n = 19). For each patient, 2 age- and gender-matched control subjects were included in the study. Data were retrieved from patients' records and analyzed retrospectively. Risk stratification was performed according to the severity of index reactions, which was initially divided as high and low risk and then further divided as immediate and nonimmediate. RESULTS: According to risk stratification, the patient and control groups were divided as follows: high-risk immediate (66.7% vs. 13%, respectively), high-risk delayed (1.4% vs. 8.3%, respectively), low-risk immediate (16.7% vs. 16%, respectively), and low-risk delayed (15.3% vs. 62.9%, respectively). Immediate reactions (odds ratio [OR]: 12.1, 95% confidence interval [CI]: 9-24.8, p < 0.001) and high-risk reactions (OR: 7.8, 95% CI: 4.1-14.6, p < 0.001) were associated with confirmed cephalosporin hypersensitivity in univariate analysis. Multivariate regression analysis indicated that immediate reactions (OR: 7.5, 95% CI: 3.3-16.8, p < 0.001) and high-risk reactions (OR: 5.2, 95% CI: 2.1-12.9, p < 0.001) were significant risk factors for the prediction of cephalosporin hypersensitivity. CONCLUSION: This model can be applied in children with suspected cephalosporin allergy. Skin testing provides diagnostic information in high-risk patients with immediate reactions and reduces the need for drug provocation testing in these patients. It is highly likely to confirm the diagnosis of low-risk patients directly with provocation tests without skin tests. High-risk and immediate reactions were found to be predictive factors for confirmed cephalosporin allergy.

ß-Lactam Allergy in Children.

OBJECTIVE: ß-lactam antibiotic allergy is the most common drug allergy in children. Most of the patients with suspected reactions to ß-lactam antibiotics can actually tolerate these drugs. The aim of this study is to evaluate clinical and laboratory characteristics of children with ß-lactam allergy and to determine cross-reactivity between penicillin and cephalosporins. METHODS: The diagnosis of ß-lactam allergy was made based on the results of skin tests and/or drug provocation tests (DPT). Penicillin allergy skin tests were performed with DAP penicillin® (Diater laboratories, Madrid, Spain), penicillin G, and ampicillin/amoxicillin preparations. Skin and provocation tests were performed with the culprit cephalosporin in addition to the penicillin skin and/or provocation tests to evaluate cephalosporin allergy. RESULTS: We found that 87.7% (71/81) of patients with ß-lactam allergy were able to tolerate the culprit drug. Among ten patients with confirmed diagnosis, two had cross-reactivity (penicillin and cephalosporin) and 8 had a various ß-lactam (aminopenicillin n=6, ceftriaxone n=2) allergies. We identified older age and early-type clinical reactions as risk factors for a confirmed ß-lactam allergy. CONCLUSION: Skin tests and DPT appear to be useful procedures in the diagnosis, and determination of an alternative safe antibiotic in patients with ß-lactam allergy. Most of the patients tolerated the drugs. A minority of the patients with confirmed allergy should avoid all ß-lactam antibiotics due to the probability of cross-reactivity.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Clarithromycin hypersensitivity in children: Is there a link with ß-lactam hypersensitivity?

BACKGROUND: Clarithromycin hypersensitivity is reported as the most common cause of non-ß-lactam antibiotic allergy in children. Clarithromycin is frequently prescribed in cases of suspected ß-lactam hypersensitivity. Oral provocation tests stand as the gold standard to confirm drug hypersensitivity as diagnostic value of skin tests is variable. We analyzed the frequency of true clarithromycin hypersensitivity ratio and its relationship with ß-lactam allergy among children with suspected clarithromycin hypersensitivity and evaluated the diagnostic value of skin tests. METHODS: The study included 160 children referred with suspected clarithromycin hypersensitivity. Clinical history and allergy workups including skin tests or/and oral provocation tests were retrieved from medical records. RESULTS: Oral provocation test confirmed clarithromycin hypersensitivity rate was 5.6% (n = 9/160). Skin tests with clarithromycin showed positivity in 32.6% (n = 29/89) of the tested patients. The sensitivity of clarithromycin skin tests was negligible, and specificity was 73.9% (95% confidence interval [CI], 64.7-81.8). Eighty-eight of the patients (55%) reported that they had previously tolerated a ß-lactam antibiotic. ß-lactam hypersensitivity was suspected in 40% (n = 64/160) of the patients (simultaneous [n = 10], sequential [n = 19], distant form [n = 35]) in relation with clarithromycin usage. ß-lactam hypersensitivity (95% CI, 2.1-70.6, p = .005) and sequential usage of clarithromycin after the development of a rash with amoxicillin-clavulanic acid (95% CI, 2.0-96.4, p = .007) were found as risk factors for confirmed clarithromycin hypersensitivity. CONCLUSION: The frequency of confirmed clarithromycin hypersensitivity was found low among suspected patients. Oral provocation test is crucial for definite diagnosis. Confirmed ß-lactam allergy may be attributed as a risk factor for clarithromycin hypersensitivity, particularly clarithromycin treatment after a developing rash with amoxicillin-clavulanic acid in sequential usage.

Plasma D-dimer : a promising indicator of COVID-19 infection severity or only an acute phase reactant.

OBJECTIVE: Serum D-dimer levels, as well as other biomarkers related to coagulation, are significantly elevated during severe community acquired pneumonia. The aim of this study is to investigate the utility of plasma D-dimer levels determining the severity of inflammation and prognosis in pediatric patients with COVID-19 infection. METHODS: We retrospectively chart reviewed medical records of pediatric patients (< 18 years of age) admitted to Istanbul Fcaulty of Medicine, Department of Pediatrics Infectious Disease Service between March 11, and June 30, 2020. We collected demographic, clinical, biochemical and radiographic data. RESULTS: A hundred and seventy-one pediatric patients (1 - 216 months of age) admitted to pediatric infecitous disease service included in this study. Patients were classified into 4 categories; 1) COVID-19 infection confirmed by PCR, 2) Suspected COVID-19 infection due to close exposure history and radiographic findings, 3) Lower respiratory tract infection other than COVID-19 confirmed with multiplex respiratory viral panel, and 4) Systemic infections other than lower respiratory tract infection. Lymphopenia was observed significantly higher in patients with COVID-19 infection compared to patients with other respiratory viral infections (p=0.06). In patients with radiographic findings concerning for COVID-19 infection, elevated serum D-dimer levels were detected significantly higher than lymphopenia (p=0.07). CONCLUSIONS: Elevated serum D-dimer levels at baseline are associated with inflammation especially in patients with COVID-19 infection with radipgraphic findings. Monitoring serum D-dimer levels may be used for early identification of severe cases in children.

'Stay at home': Is it good or not for house dust mite sensitized children with respiratory allergies?

BACKGROUND: Lockdown was imposed for children for 75 days in Turkey to limit the spread of COVID-19. During this period, children have to stay indoors, which might probably increase their exposures to indoor allergens and pollutants. Besides, reduced exposures to respiratory tract infections and outdoor pollutants might be favorable outcomes of this lockdown period. We evaluated the effects of the lockdown on house dust mite (HDM)-sensitized children with respiratory allergies. METHODS: Three-month clinical and medication data of 165 mild-moderate asthmatic children with or without allergic rhinitis (AR), who were grouped according to their HDM sensitization status, were retrieved from patient records. Demographics, asthma control tests, nasal visual analog scores, and outdoor air quality monitoring data were used for assessments in comparisons with the same period in the previous year. RESULTS: Eighty-four patients had asthma, and 81 patients had asthma with AR. Sensitization to HDM was present in 61.8% of the children. Patients experienced reduced numbers of upper respiratory tract infections (P = .008) and reduced asthma exacerbations (P < .001) compared with the same period in the previous year. Asthma control tests were significantly improved (P < .001), and cumulative inhaled corticosteroid usages were significantly reduced (P < .001). Noteworthily, nasal symptoms were significantly worsened in HDM-sensitized asthmatics with AR (P < .001). CONCLUSIONS: This study highlighted that reduction in respiratory tract infections and outdoor pollution may play roles in asthma control and prevent exacerbations despite continuous indoor allergen exposure. Besides, worsening of nasal symptoms in HDM-sensitized asthmatics with AR implies the importance of indoor avoidance measures for AR control.

Behind the scene: Paracetamol hypersensitivity in children.

BACKGROUND: Paracetamol, a non-steroidal anti-inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity. METHODS: Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX-1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross-intolerance hypersensitivity. A subsequent OCT with a selective COX-2 inhibitor was performed in those cross-intolerant patients to find out a safe alternative drug. RESULTS: Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross-intolerant after OCT with a COX-1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross-intolerant patients, a safe alternative non-steroidal anti-inflammatory drug was identified after an OCT with a selective COX-2 inhibitor. CONCLUSION: OCT stands as the gold-standard procedure in verifying the diagnosis of patients with paracetamol-induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

BACKGROUND: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population. METHODS: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS. RESULTS: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV1 percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS. CONCLUSION: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.