Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

A practical method of drug provocation testing to prove tolerance to alternative drugs in drug hypersensitivity

Background/aim: Drug provocation tests (DPTs) are the gold standard method performed at the end of a stepwise approach in a drug allergy workup. Drug provocation tests are administered as a single drug on a test day. Testing more than one drug in a day is a feasible option and could be a safe and time- and manpower-saving procedure in well-selected patients. The aim of the present study was to investigate the efficacy and safety of performing a DPT with two or three alternative drugs in one test day (Hacettepe method). Materials and methods: Adult patients who were admitted with drug hypersensitivity between August 2010 and December 2016 and underwent DPTs with the described method were included. The method was based on performing DPTs with two or three different, alternative drugs on the same test day. Data was obtained from standard drug provocation test forms and from patient files. Results: A total of 1448 DPTs were performed by the Hacettepe method in 1131 patients. The reaction rate was 5.45% (n = 79), and none of the reactions were severe. The Hacettepe method saved 19.95 DPTs per month which was a considerable time savings. Conclusion: In cases of proven drug hypersensitivity reactions, performing a drug provocation test with a combination of two or three different, alternative drugs instead of one saved time and manpower and was a safe procedure. We recommend implementing this method in drug allergy workups.

The Effect of Asthma Severity on Perinatal Outcomes: A Tertiary Hospital Experience.

OBJECTIVE: To evaluate the effect of asthma severity and disease exacerbation on pregnancy outcomes. MATERIALS AND METHODS: Pregnancies were classified into 3 groups as mild (n=195), moderate (n=63), and severe (n=26) according to preconceptional asthma severity. Demographic features, clinical characteristics, and perinatal outcomes were compared between the groups. Delivery characteristics and pregnancy outcomes were also compared between the pregnancies with or without asthma exacerbation (43 and 241 pregnancies, respectively). RESULTS: Worsening of symptoms during pregnancy was higher in moderate and severe asthma groups (p<0.001). Rates of spontaneous abortion, fetal structural anomaly, preterm delivery, preeclampsia, fetal growth restriction (FGR), oligohydramnios, gestational diabetes, and intrauterine fetal demise were higher in moderate and severe asthma groups (p-values were < 0.001, 0.01, 0.008, 0.02, 0.01, < 0.001, < 0.001, and 0.007, respectively). Admissions to neonatal intensive care units and neonatal complication rates were higher among moderate and severe asthma groups (p=0.035 and < 0.001). Spontaneous abortion, preterm delivery, preeclampsia, FGR, oligohydramnios, and neonatal complication rates were higher (p<0.001) in the group with exacerbated symptoms. CONCLUSION: Moderate to severe asthma before pregnancy and the exacerbation of asthma symptoms during pregnancy may lead to increased rates of perinatal complications.

IgE-mediated food allergy throughout life

Food allergy (FA) has become an increasing problem throughout the world. Over the last 2 decades, the frequency of FA has increased in both children and adults. The prevalence differs according to the research methodology, age, and geographic regions, ranging between 2.0% and 10.0%. The most common form of FA is immunoglobulin E (IgE)-mediated FA. In this form, patients may present with life-threatening conditions, such as anaphylaxis, or milder conditions, such as urticaria, angioedema, sneezing, and nausea alone. The gold standard in the diagnosis of FA is oral provocation tests. Epidermal skin prick tests and specific IgE measurements, as well as component-resolved diagnostic techniques are helpful in the diagnosis and follow-up of patients. In this review, the epidemiology, diagnosis, follow-up, and prognosis of IgE-mediated FA in children and adults were discussed and some specific forms of FA, such as pollen FA syndrome, alpha-gal allergy, and food-dependent exercise-induced anaphylaxis were explained.

Factors associated with severe lung disease in an adult population with cystic fibrosis: a single-center experience

Background/Aim: The patients with cystic fibrosis (CF) are living longer compared to the past, but respiratory failure is still the most common cause of mortality. The aim of this study is to investigate factors associated with severe lung disease in a cohort of adult patients with CF. Materials and methods: Demographic data, clinical and laboratory findings of the patients aged 18 years and more were collected and the patients were grouped according to forced expiratory volume in 1 s (FEV1) as severe group: <40% and nonsevere ≥40%. Associations were investigated between groups and clinical outcomes. Results: A total of 76 patients were enrolled in the study. The mean age was 24.5 ± 5.25 years and 36 (47.4%) patients were female. In the severe group; the mean age was higher (27.1 ± 6.0 vs 23.6 ± 4.7, P = 0.013), the median Chrispin-Norman score of severe lung disease group was higher (14 (6­22) vs 5.5 (0­20), P < 0.001), hospitalization at least once in a year for intravenous antibiotic was more common (12/18 (66%) vs 19/58 (32%), P = 0.014). There was a positive correlation between body mass index (BMI) and lung function, indicating that lower nutritional status was related to lower FEV1, r2 = 0.21, P < 0.001. The median FEV1% was lower in patients with CF-related diabetes (38 (14­95) vs 66 (13­121), P = 0.042). Dornase alpha use and physiotherapy rate were higher in severe lung disease group (P = 0.008 and P < 0.001, respectively). Conclusion: Lower BMI, older age, presence of CF-related diabetes, higher radiologic scores, use of dornase alpha and physiotherapy and higher hospitalization rate for intravenous antibiotic therapy are significantly associated with severe lung disease.

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

BACKGROUND: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs. METHODS: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy. RESULTS: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups). CONCLUSIONS: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.

Growing-rod Graduates With Idiopathic Early-onset Scoliosis Have Comparable Exercise Tolerance to Patients With Surgically Treated Adolescent Idiopathic Scoliosis.

BACKGROUND: Growing-rod (GR) treatment is the current standard for progressive idiopathic early-onset scoliosis (I-EOS) in young children. Despite good radiographic outcomes, the impact of scoliosis treatment on pulmonary functions is not well-defined in this patient population. The aim of this study was to evaluate pulmonary functions and exercise tolerance in I-EOS patients graduated from GR treatment and to compare them with age-matched, surgically treated adolescent idiopathic scoliosis (AIS) patients and healthy controls. METHODS: Eight GR graduates with I-EOS with pulmonary function tests and complete radiographic results were compared with a group of 9 thoracic AIS patients at least 2 years out from posterior fusion. Both groups were also compared with a set of 10 healthy individuals. All subjects underwent cardiopulmonary exercise testing and spirometry to evaluate pulmonary function. RESULTS: Age, sex, height, arm span, weight, residual deformity, and level of instrumentation in GR and AIS patients were similar. In the GR group, forced vital capacity % and forced expiratory volume in 1 second % values were reduced compared with the healthy controls and AIS group (P<0.001, <0.001 and 0.036, 0.046, respectively). Breathing reserve index at lactate threshold (BRILT) was higher in GR and AIS patients (P=0.001 and 0.002, respectively), and was similar between GR and AIS patients (P=0.916). Heart rate at lactate threshold was higher in GR and AIS groups compared with controls (P<0.001 and 0.001, respectively). CONCLUSIONS: AIS and GR patients demonstrated reduced pulmonary reserve and exercise tolerance compared with their peers with no spinal deformity. However, exercise tolerance of I-EOS patients treated with the GR method was similar to that of operated AIS patients. These results suggest a positive impact of GR treatment in children with I-EOS. LEVEL OF EVIDENCE: Level III-cross-sectional comparative study.

Screening instrument to identify skin prick test-negative patients with asthma and/or rhinitis.

INTRODUCTION: To the best of our knowledge, there is no prediction tool for determining respiratory allergy in patients with asthma and/or rhinitis. OBJECTIVES: As such, this study aimed to develop an instrument for identifying skin prick test (SPT)-negative patients with asthma and/or rhinitis. METHODS: This cross-sectional study screened 510 consecutive patients diagnosed with asthma and/or rhinitis between November 2009 and May 2011 in Ankara, Turkey. A structured questionnaire was the screening tool that was administered during the initial visit by the treating specialist and compared with a SPT result. All 15 variables were analysed using the logistic regression model to obtain ß values (a score) for each variable. Each variable had a score, and scores were summed up to obtain final score for each patient. RESULTS: The study included 363 patients, of which 165 (45.5%) were SPT positive. The final model included 13 variables. The lowest and highest scores were -21 and 26. A total score of 5.5 had sensitivity of 63% and specificity of 80%. The area under the receiver operating characteristic curve was 0.78. The histogram of the total scores for the study population was bimodal. CONCLUSIONS: We designed a highly specific 13-item instrument for identifying SPT-negative patients. It may be used in middle income countries where allergy testing is expensive, not reimbursed or few allergy clinics are available. We think that our idea is interesting, that needs further research.

Paper #3: Can TGR change the natural history of pulmonary functions in EOS? Is Radiological Straightness Correlated with Normal Lung Development?

Even though traditional growing rod (TGR) patients score lower in exercise tolerance and spirometry compared to age-matched controls, their pulmonary functions are similar to those of instrumented adolescent idiopathic scoliosis (AIS) patients.

Protective efficacy of sunglasses on the conjunctival symptoms of seasonal rhinitis.

BACKGROUND: Although allergen avoidance can lead to significant improvements in symptoms of allergic rhinitis, there are very few studies in this area. Sunglasses could be effective for protection of eyes from pollen as a cheap, comfortable, and simple avoidance option for allergens. The aim of this study is to determine if wearing sunglasses can decrease ocular symptoms. METHODS: Ocular symptomatic patients (39 total) who had a confirmed history of seasonal rhinitis by skin prick tests and negative skin prick tests for perennial allergens were included in the study. The duration of the study was 4 weeks with 3 required visits. At the onset of the 1-week run-in period, patients were randomized and divided into 2 groups. Group I (n = 18) received topical aqueous nasal budesonide regularly and loratadine once daily as a rescue medication. Group II (n = 21) wore sunglasses during daytime as an addition to this medication. Subjective data included a daily diary recording nasal and ocular symptom scores and antihistamine need during the study period. RESULTS: Sunglasses significantly reduced ocular symptoms (p = 0.002) and use of antihistamines (p = 0.009). CONCLUSION: Sunglasses are an inexpensive and simple treatment for patients with allergic conjunctivitis.

Non-steroidal anti-inflammatory drug hypersensitivity in adults and the factors associated with asthma.

BACKGROUND: Characteristics of non-steroidal anti-inflammatory drug (NSAID)-hypersensitivity (NH) associated with underlying/accompanying diseases has not been studied in Turkey. In addition, the factors associated with asthma in NH patients are not well known. The present study aimed to investigate the relationship between NH and chronic urticaria, rhinitis/rhinosinusitis, and asthma in an effort to identify NH phenotypes. The study's secondary aim was to identify the factors associated with asthma in NH patients and the NSAID reaction pattern in asthmatics. METHODS: Data for 1137 NH patients in our hospital's allergy clinic database were retrospectively analyzed. Patients were divided into 5 groups based on their accompanying diseases (chronic urticaria, asthma, rhinitis/rhinosinusitis). Asthmatic patients were compared to non-asthmatic patients to identify the factors associated with asthma. RESULTS: Reaction patterns and patient characteristics in each group differed from those in the reference group (NH only group). Asthma in patients with NH was associated with female gender, sinonasal polyposis/polyp surgery, rhinitis/rhinosinusitis, NSAID-induced rhinitis/asthma or a blended reaction pattern, immediate reaction following NSAID intake, self-reported history of food allergy, and family history of asthma; the odds ratios and 95% CIs were 1.35 (1.02-1.78), 13.52 (8.74-20.9)/10.94 (6.73-17.77), 12.06 (9-16.17), 15.28 (10.45-22.36)/2.43 (1.70-3.45), 1.76 (1.31-2.35), 1.49 (1.04-2.14), and 3.1 (2.35-4.08), respectively. The characteristics of the asthmatic patients that had urticaria/angioedema-type reactions to NSAID intake (pseudo Samter's syndrome) differed from those in the asthmatics with rhinitis/asthma-type reactions. CONCLUSIONS: Chronic urticaria, rhinitis, and asthma commonly accompany NH. NSAID response patterns in NH patients may help differentiate groups of patients. The present study identified factors associated with asthma in NH patients and observed that there seems to be different phenotypes of Samter's syndrome, for which a new classification scheme was proposed.

The analysis of Hymenoptera hypersensitive patients in Ankara, Turkey.

BACKGROUND: Although there are some published data about the prevalence of honeybee and vespid venom allergy from Turkey, there has been no report about Hymenoptera venom immunotherapy practice. Our aim was to determine the characteristics of Hymenoptera venom hypersensitivity and venom immunotherapy practice in Ankara, Turkey. METHODS: Demographic and clinical data, intradermal test, and serum specific IgE results of 65 Hymenoptera venom allergic patients who were followed up in our department from February 2005 to August 2009 were analysed. RESULTS: Serum Vespula specific IgE class (p:0.02) and Apis specific IgE class were high (p<0.0001) and Apis intradermal test results were positive (p<0.001) in accordance with the patients' history. However, intradermal test results with Vespula were not consistent with self-reported Hymenoptera type (p:0.15). While Apis specific IgE and intradermal test results were correlated with each other (rho: 0.59, p<0.0001), Vespula specific IgE and intradermal test results were not (rho: 0.2, p:0.17). Intradermal test against Vespula did not discriminate between Apis and Vespula hypersensitive patients. There were no significant differences when the grade of reaction and specific IgE and intradermal test results were compared between Apis and Vespula. CONCLUSIONS: Vespula venom hypersensitivity was more common among our patients. However, intradermal tests with Vespula had limited diagnostic sensitivity and were not correlated with serum specific IgE. Based on our results and previous reports, we recommend that negative skin test responses, especially with Vespula, need further investigation.