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.

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.

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.

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.

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.