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: 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.