Background: In this study, we aimed to evaluate the losses in the gains of children who had to discontinue their modulator therapies due to drug delivery procedures. Methods: Demographic, clinical, microbiologic, radiologic, and pulmonary function test parameters of twelve CF children, were evaluated. Parameters were divided into three groups as ‘before treatment’ (BT), ‘during treatment’ (DT) and ‘after interruption of treatment’ (AT) to show differences between. Results: There was a significant increase in forced expiratory volume in 1 s (FEV1) z-score, body mass index (BMI) z-score and Cystic Fibrosis Questionnaire-Revised respiratory domain score (CFQR-RS) of DT compared with the values BT (p=0.001, p=0.012, p<0.001; respectively). It was found that FEV1 z-score, BMI z-score and CFQR-RS of DT decreased significantly compared with the values AT (p=0.003, p=0.01, and p<0.001, respectively). When post and pre-treatment levels were compared, there was no significant difference between FEV1 z-score (p=0.07), BMI z-score (p=0.56), CFQR-RS (p=0.7). Half of patients had percent-predicted forced expiratory volume levels with a drop of more than 20%. It was also detected that Pseudomonas aeruginosa colonization was a significant factor in degradation of FEV1 z score to the lower pre-treatment levels. Conclusion: This is the first retrospective detailed study about discontinuation of modulatory therapies in children. Our study shows the importance of treatment continuation as well as the patients access to these drugs. We hope that this study will raise awareness about the regular long-term use of modulator therapies. To make these therapies available worldwide, immediate action is required.

Background: Primary ciliary dyskinesia (PCD) is a genetic disease characterized by recurrent respiratory tract infections. Although the pulmonary manifestations of the disease are well defined, data on otorhinolaryngological complications are insufficient. This study aimed to reveal the prevalence, clinical course and related factors of ear-nose-throat (ENT) manifestations in PCD patients. Methods: PCD patients followed in the ENT department of our center for the last 21 years were included in this retrospective observational study. The frequency of sinonasal and otological diseases, the relationships between clinical and demographic data, and possible risk factors for otorhinolaryngological findings were investigated. Results: Of the 121 patients recruited, 53% were male and the median age at diagnosis was 7 (1 month - 20 years) years. The most common ENT manifestation was otitis media with effusion (OME) (66.1%), followed by acute otitis media (43.8%), acute rhinosinusitis (ARS) (28.9%), chronic rhinosinusitis (CRS) (27.3%), and chronic otitis media (10.7%). The mean age of patients with ARS (18 vs. 16 years, p=0.045) and CRS (19 vs. 16 years, p=0.028) was higher than those without. The annual number of ARS was positively correlated with age (r= 0.170, p=0.06). A total of 45 patients had audiograms and the most common finding was conductive hearing loss (53.3%). OME significantly increased this risk of tympanic membrane injury (OR: 8.6, 95% CI: 3.6-20.3, p<0.001). Although not statistically significant, hearing loss was more common in patients who had OME compared to those who did not (76.5% vs. 45.5%, OR: 3.9, 95% CI: 0.94-16.2, p=0.062). Conclusions: Otorhinolaryngologic diseases are common in PCD patients and the awareness of ENT physicians should be expanded. Our study showed that with increasing age, patients may present with ARS and CRS more. Presence of OME is the most important risk factor for tympanic membrane damage and the most common type of hearing loss is conductive failure.

Background: Cystic fibrosis (CF) is reported to be a risk factor for drug hypersensitivity. However, there is conflicting data about true prevalence of drug allergy in children with CF. Methods: The suspicious drug hypersensitivity reactions (DHR) of children with CF were enquired by European Network for Drug Allergy (ENDA) questionnaire and skin tests and/or drug provocation tests were performed according to established guidelines. Results: Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study, from whom 22 patients with 24 suspected DHRs were evaluated. Most of the suspected DHRs were non-immediate (n=16, 66.6%) type and the offending drugs were amoxicillin clavulanic acid (n=7), macrolides (n=4), trimethoprim sulfamethoxazole (TMP/SMX) (n=2), piperacillin tazobactam (n=1), pancrelipase (n=1) and ursodeoxycholic acid (n=1). Eight (33.3%) of the DHRs were classified as immediate [ceftriaxone (n=2), ceftazidim (n=2), meropenem (n=1), ambisome (n=2), vancomycin (n=1)]. The main presenting clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%) and vomiting (8.3%). Nine skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs were performed and none of the skin tests revealed a positive result, however 2 DPTs with TMP/SMX were positive. Conclusion: Actual drug allergy was demonstrated in 2 of 219 patients (0.9%) with nonbeta-lactam antibiotics. These results conflict with previous researches that showed higher drug allergy rates but were consistent with some recent studies. Numerous and long-term use of multiple drugs during management of cystic fibrosis may contribute to tolerance development.

INTRODUCTION: Recurrent pulmonary infections, wheezing and stridor due to swallowing dysfunction, esophageal dysmotility, gastroesophageal reflux, tracheomalacia and bronchomalacia are frequently seen complications after esophageal atresia and tracheo-oesophageal fistula (EA-TEF) surgeries. This study aimed to investigate the frequency and causes of respiratory problems and to evaluate the factors that affect respiratory morbidity in patients who had undergone EA-TEF repair in a tertiary referral center. METHODS: Preoperative and postoperative records of patients with EA, TEF+EA and isolated EA were examined retrospectively. Accompanied diseases and swallowing dysfunction symptoms were questioned. Bronchoalveolar lavage results were investigated if the patient had flexible bronchoscopy. RESULTS: A total of 71 children with EA were included in the study, and seven patients who did not have follow-up after surgery were excluded. 46 of the 64 patients continue regular follow-up visits in our department. Male sex, primary EA repair in another center, EA type C, accompanying genetic anomalies, severe tracheomalacia, late per oral feeding (1 year after surgery), and severe GER were found to cause significantly higher incidence of coughing, recurrent wheezing, recurrent pneumonia, and bronchiectasis despite surgical and medical treatments (p = 0.048, p = 0.045, p = 0.009, p = 0.029, p = 0.025) CONCLUSİON: Even if anatomical anomalies are corrected by surgery in patients who underwent EA repair, precautions can be taken for GERD, laryngotracheomalacia, and swallowing dysfunction, and effective pulmonary rehabilitation can be initiated with early multidisciplinary approach before the development of respiratory tract symptoms.

Cystic fibrosis is an autosomal recessive disease caused by CFTR gene mutations. Despite having the same mutation, CF patients may demonstrate clinical variability in severity and prognosis of the disease. In this study, we aimed to determine differentially expressed genes and associated molecular pathways between mild and severe siblings with same genotype. We performed targeted real-time PCR based transcriptomic analysis of nasal epithelial cells obtained from two families with two siblings with Class II mutations (F508del/F508del) and (F508del/G85E), one family with three siblings with Class IV mutation (I1234V/I1234V). In severe siblings with Class II mutations, TNFRSF11A, KCNE1, STX1A, SLC9A3R2 were found to be up regulated. CXCL1, CFTR, CXCL2 were found to be down regulated. Inflammation-immune response related signaling pathways such as IL-17, NF-kappa B, TNF, NOD-like receptor signaling were identified. In the severe sibling with Class IV mutation; inflammation and immune response-related pathways were discovered. Also, AGE-RAGE and TLR signaling were found to be specific to Class IV group. Comparison of CF patients to non-CF control; showed that ICAM1 was up regulated whereas EZR, TNFRSF1A, HSPA1A were down regulated in patients. In addition, a significant positive correlation was determined between differentially expressed genes in AGE-RAGE, cytokine-cytokine receptor interaction, insulin resistance and hepatic involvement in CF patients. As a result of this study, differentially expressed genes and associated pathways responsible for clinical severity among affected siblings carrying the same mutation were identified. The results will provide an opportunity for the development of novel target molecules for treatment of disease.

Objectives: To evaluate the risk factors of recurrent pulmonary exacerbation and poor prognosis in children with idiopathic pulmonary hemosiderosis (IPH).  Methods: In this multicenter study, 54 patinets with diagnosis of IPH included. Medical records were retrospectively reviewed from three tertiary care hospitals between 1979 and 2019. Also, current information and the long-term progress of patients was determined by contacting the families by telephone. Results: A total of 54 children were included. The median age of onset of symptoms was 4.5 ± 3.8 years. The median time from onset to diagnosis was 0.9 years ± 2.2. The mean number of recurrent episodes per child in the recurrence-positive group was 3.55 (1-15). Univariate analysis demonstrated that patients presenting with hypoxia or requiring transfusion at the time of presentation had significantly more recurrence episodes (P=0.002). Multivariate analysis showed that the presence of hypoxia at the time of initial presentation was a significant independent predictor of recurrent episodes (P=0.027). The median follow-up was 3.3 ± 4.8 years (0.75 months-27 years). There was a significant relationship between the presence of hypoxia, transfusion history, ANA positivity, and elevated transaminases at the time of initial evaluation and treatment response. Conclusions: The present study provides important information on the clinical course and outcome of pediatric IPH, and substantial information regarding factors that affect recurrent exacerbations and prognosis. Demonstrating of hypoxia as an independent risk factor in recurrence episodes could be guide physicians in the planning of treatment strategies.