Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations.

BACKGROUND: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. CONCLUSION: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

Quality of life in children with non-cystic-fibrosis bronchiectasis.

BACKGROUND: Non-cystic-fibrosis bronchiectasis (non-CF BE) continues to be a problem in developing countries and it is therefore important to examine and assess this disease. OBJECTIVES: The aims of this prospective study were to evaluate the health-related quality of life (HRQOL) in non-CF BE children and also to assess the risk factors associated with HRQOL. METHODS: Forty-two non-CF BE patients between the ages of 9 and 18 years were enrolled in the study. All recruited patients completed the generic Short-Form-36 (SF-36), the St. George's Respiratory Questionnaire (SGRQ) for disease-specific QOL scale and forms on socioeconomic status (SES). The extent and severity of CT abnormalities were evaluated by using the modified Bhalla scoring system. Association between HRQOL questionnaires and demographic variables, pulmonary function test, high-resolution CT scores and SES were evaluated. RESULTS: SF-36 and SGRQ subscales all correlated inversely with each other (SF-36 physical component summary with SGRQ symptoms score: r = -0.466, p = 0.001, activity score: r = -0.666, p = 0.000 and impact score: r = -0.667, p = 0.000. SF-36 mental component summary with SGRQ symptoms score: r = -0.396, p = 0.005, activity score: r = -0.533, p = 0.000 and impact score: r = -0.512, p = 0.000). There was an inverse correlation between SGRQ symptoms scores and the duration of regular follow-up (r = -0.3, p = 0.04). The symptoms subscale of SGRQ correlated positively with low values for pulmonary function testing (r = -0.417, p = 0.003) and frequent antibiotic requirements (r = 0.303, p = 0.035). CONCLUSIONS: Early diagnosis and regular follow-up of children with non-CF BE is important for improving their QOL. As expected, the severity and frequency of symptoms are inversely related to the pulmonary function and the QOL scores. A disease-specific questionnaire should be developed to monitor QOL in children with non-CF BE.

Intrinsic endobronchial obstructions in children from Turkey: evaluation of 2,555 flexible bronchoscopic procedures.

BACKGROUND: Endobronchial obstructions are rarely seen in children and are often misdiagnosed resulting in delay of definitive treatment. A variety of diseases can cause endobronchial obstructions in childhood, but data is limited as to the frequency, distribution and clinical characteristics of endobronchial obstructions diagnosed with flexible bronchoscopy (FB). OBJECTIVE: To document endobronchial obstructions detected by FB. METHODS: FB results from three pediatric pulmonology centers in Istanbul were evaluated. RESULTS: A total of 2,555 children underwent an FB procedure during the study period. Endobronchial obstructions were detected in 10% (n = 256) of the patients. Among FB in patients who had endobronchial obstructions, the four most common indications for bronchoscopy were persistent infiltrations (30%, n = 72), persistent wheezing (28%, n = 70), chronic cough (26%, n = 66) and atelectasis (23%, n = 59). The most common endobronchial obstructions detected in the patients were aspirated foreign bodies (35.9%, n = 92), endobronchial tuberculosis (31.6%, n = 81), mucous plugs occluding airway (16.7%, n = 43) and granulation scars (6%, n = 16). Other pathologies included hydatid cysts (n = 5), hemangiomas (n = 5), tumors (n = 5), submucosal nodules (n = 5) and polyps (n = 4). Endobronchial obstructions were most commonly located in the right bronchus (51%, n = 130) followed by the left bronchus (33%, n = 85), bilaterally (8%, n = 21) and trachea (8%, n = 20). CONCLUSIONS: Endobronchial obstructions can be caused by a number of different diseases which require various medical or surgical treatments. In the presence of clinical or radiological findings suggesting an endobronchial obstruction, FB should be performed promptly.

Bronchoscopic evaluation of unexplained recurrent and persistent pneumonia in children.

BACKGROUND: Persistent or recurrent pneumonia in children can pose a significant challenge to paediatricians and respiratory physicians. AIM: The aim of this study is to determine the role of flexible bronchoscopy (FB) in evaluation of recurrent or persistent pneumonia that remain otherwise unexplained by non-invasive diagnostic tests in children. METHODS: Retrospective evaluation of patients who underwent FB with an indication of recurrent or persistent pneumonia from 1997 to 2011. RESULTS: Among 2600 FB procedures, 434 (17%) were performed with the indication of recurrent or persistent pneumonia. There were 237 (54%) boys. Median age at presentation was 84 months, and median duration of symptoms was 9 months. FB led to specific diagnosis in 33% of the cases. The most common diseases diagnosed by FB were malacia disorders (n: 32, 7%), aspirated foreign body (n: 30, 7%), endobronchial tuberculosis (n: 20, 5%), congenital airway anomalies (n: 14, 3%), mucus plugs (n: 14, 3%), pulmonary haemosiderosis (n: 12, 3%) and middle lobe syndrome (n: 11, 3%). During FB, only 6% of the patients had minor complications such as transient hypoxia, stridor and tachycardia. CONCLUSIONS: In our study, FB proved to be a safe and effective tool in evaluation of children with persistent or recurrent pneumonia. FB is indicated for children with recurrent or persistent pneumonia where the underlying diagnosis remains unclear even after non-invasive diagnostic tests.

Flexible bronchoscopy as a valuable tool in the evaluation of infants with stridor.

The aim is to determine clinical characteristics, flexible bronchoscopy (FB) findings including associated airway abnormalities and other conditions, treatment modalities and long term follow-up of children with congenital stridor. Medical records of children, who underwent FB for the evaluation of stridor between 1 January 2004 and 31 December 2009 were retrospectively reviewed. Demographic characteristics, symptoms and physical examination findings at presentation, FB findings, follow-up data including the time to resolution of symptoms and treatment modalities, presence of associated conditions were assessed. 109 children were enrolled to the study. Laryngomalacia was the most common etiology for stridor. Laryngomalacia was isolated in 37 patients and 54 patients had secondary airway lesions (SALs). Diagnoses other than laryngomalacia such as subglottic hemangioma, subglottic web, isolated tracheomalacia were found in 18 patients. In 90 % of patients, stridor resolved before 3 years of age without any surgical intervention and there was no significant difference in terms of the persistence of stridor between patients with isolated laryngomalacia and associated SALs. Duration of stridor was significantly longer in both patients with neurological abnormalities and reflux symptoms. Surgical procedure was performed in 19 of the patients. There is a high incidence of SALs in patients with laryngomalacia. FB is helpful for identifying anomalies requiring surgical treatment.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Comparison of piperacillin tazobactam and cefoperazone sulbactam monotherapy in treatment of febrile neutropenia.

BACKGROUND: Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer. PROCEDURE: The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. RESULTS: One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups. CONCLUSION: CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer.

Immunosuppressive treatment in children with acquired aplastic anemia.

OBJECTIVE: Immunosuppressive treatment (IST) is an alternative for children with acquired aplastic anemia (AA) that do not have HLA-matched donors. The objective of this study was to evaluate the outcome of IST in children with acquired AA. MATERIAL AND METHODS: The study included 18 pediatric acquired AA patients that were retrospectively evaluated. The patients either did not have an HLA-matched related donor or were unable to undergo transplantation within 6 months despite having an HLA-matched donor. RESULTS: In all, 6 of the patients were characterized as very severe AA, 6 as severe AA, and 6 as moderate AA. Mean duration of follow-up was 44.5 months. In total, 9 patients that could not be treated with equine anti-thymocyte globulin (hATG) following diagnosis received high-dose methylprednisolone treatment. Among the 6 very severe AA patients, 2 achieved complete remission (22%); the other 16 patients received hATG+cyclosporine and short-term methylprednisolone. In total, 4 of the patients died during the first month of treatment. Of the remaining 12 patients, 3 responded to the treatment (25%). Of the 9 patients that did not respond after 3 months of treatment, 7 received a second course of immunosuppressive treatment with rabbit ATG (rATG)+cyclosporine and short-term methylprednisolone; 2 of the 7 patients responded (22%), but 5 did not respond to any treatment. Median survival among the patients was as 64 ± 8 months CONCLUSION: Combination IST with ATG+cyclosporine and low-dose methylprednisolone was an effective treatment in the pediatric acquired AA patients with non-identical HLA donors. In the patients that couldn't be treated with ATG high-dose methylprednisolone treatment was safe and effective.

Collaboration between two CF centers; one in USA and one in Turkey before and during CoV2 pandemic.

To address the discrepancy in the quality of care and outcomes between cystic fibrosis centers (CFCs) in high-income countries and limited resources countries (LRCs), a collaboration between our team at the University of Michigan CFC (UMCFC) and a CF center in Turkey (Marmara University CFC [MUCFC], Istanbul) was established. The collaboration included evaluation of all aspects of care and initiation of quality improvement (QI) measures. Teaching and implementing QI tools has led to start of improvement in MUCFC care. Close monitoring and sharing resources like UMCFC algorithms, protocols, and QI processes were done.

Acute liver failure, autoimmune hepatitis, and leptospirosis: a case report.

The etiology of acute liver failure varies widely in children, but the most common causes are viral hepatitis, drugs, and toxins. We report herein a case of autoimmune hepatitis and acute liver failure caused by leptospirosis, which is involved rarely in etiology.

Brucellosis presenting with pancytopenia due to hemophagocytic syndrome.

Reactive hemophagocytic syndrome is clinically characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, and is histologically characterized by excessive proliferation and activation of histiocytes or macrophages. It can occur with systemic infections, immunodeficiency, or underlying malignancy. Brucellosis is one of the rare causes of hemophagocytosis. Herein we report an 11-year-old male with pancytopenia due to hemophagocytosis during the course of brucellosis that responded favorably to therapy. Although rare, hemophagocytosis should be considered as a possible cause of pancytopenia in patients with brucellosis, especially in regions where brucellosis is frequently encountered.

Study protocol: the ear-nose-throat (ENT) prospective international cohort of patients with primary ciliary dyskinesia (EPIC-PCD).

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10 000. It affects mainly the upper and lower airways due to impaired mucociliary clearance. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems, although the ENT clinical phenotype may present great variability. Despite that, data on PCD ENT manifestations are scarce and based on small single-centre studies. To date, we know little about the spectrum and severity of PCD ENT disease, its association with lung disease, its course over life and its determinants of prognosis.This study protocol describes the aims and methods of the first prospective, observational, multinational cohort study focusing on ENT disease in patients with PCD. METHODS AND ANALYSIS: The ENT prospective international cohort of patients with PCD (EPIC-PCD) is a prospective standardised observational clinical cohort set up as a multinational multicentre study, embedded into routine patient care. It aims to longitudinally characterise ENT disease in patients with PCD and its association with lung disease, and to identify determinants of its prognosis. Patients of all ages, diagnosed with PCD who undergo an ENT clinical assessment at least once a year at one of the participating centres will be invited to participate. Collected data include diagnostic test results, results of ENT examinations, lung function measurements, information on management of ENT disease and patient-reported data on clinical symptoms and health-related quality of life (QoL). Data are collected using the standardised PCD-specific FOLLOW-PCD form and the validated QoL-PCD questionnaire. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committees at all participating centres, based on local legislation. The results of the study will be published in scientific journals, presented at scientific conferences and disseminated to participants and national patient organisations. TRIAL REGISTRATION: NCT04611516.

Chronic intermittent form of isovaleric acidemia mimicking diabetic ketoacidosis.

Isovaleric acidemia is a rare autosomal recessive inborn error of leucine metabolism. Two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. The acute type is observed more frequently and is more fatal. We report the case of a girl in childhood who presented with hyperglycemia and metabolic acidosis with an increased anion gap; and preliminarily diagnosed as diabetic ketoacidosis, but further investigation revealed chronic intermittent isovaleric academia. This case is of interest because of the rarity of this presentation. The importance of thinking for inborn errors of metabolism in children with metabolic acidosis in late childhood is emphasized.

Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia.

BACKGROUND: In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases. METHODS: Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as "success" and improvement with modification of the initial treatment and death was defined as "failure". RESULTS: Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group. CONCLUSIONS: Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.

The role of Treg cells and FoxP3 expression in immunity of ß-thalassemia major AND ß-thalassemia trait patients.

There is increased susceptibility to infections in ß-thalassemia. Changes in T- and B-lymphocyte subsets and functions, defective chemotaxis, and phagocytosis of neutrophils and macrophages have been described in these patients. Regulatory T cells (Treg cells) play a crucial role in the maintenance of immunological self-tolerance. The FOXP3 gene is specifically expressed on Treg cells. Increased antigenic stimuli due to repeated blood transfusions might change the Treg cells and FOXP3 percentage in ß-thalassemia. Immune functions of peripheral blood lymphocytes, percentage of Treg cells (defined as CD4(+)CD25(+)FoxP3(+)) were evaluated in 30 ß-thalassemia major, 30 ß-thalassemia trait, and 20 healthy children. Percentage of CD4(+)CD45RA(+) cells were increased in ß-thalassemia trait compared to both ß-thalassemia major and controls, whereas percentage of CD4(+)CD45RO(+) cells were higher in ß-thalassemia major and trait patient compared to controls. Percentages of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+) Treg cells were increased only in ß-thalassemia major patients compared to controls (P = .001 and P = .0001, respectively). T lymphocytes express activated phenotype both in ß-thalassemia major and trait patients. However, only in ß-thalassemia major patients who were exposed to chronic antigenic stimulus as a result of repeated blood transfusions was an increase observed in Treg cells, which might suppress immune activation status.

Caregiver burden in children with cystic fibrosis and primary ciliary dyskinesia.

INTRODUCTION: Caregiver burden impacts both the social and economic framework of society. Cystic fibrosis (CF) causes significant caregiver burden, but the current data is scarce. In the case of primary ciliary dyskinesia (PCD), even less is known. This study aims to compare the caregiver burden of the parents of patients with CF and PCD. METHODS: Patients with CF and PCD between the ages of 6 to 13 and their parents were included. Patients' clinical information and parents' demographics were recorded. Caregiver burden was measured with Zarit Caregiver Burden Scale (ZCB), while the quality of life (QOL) was measured with CFQOL-revised (CFQOL-R) and PCD QOL questionnaire as the patients' age and diagnosis indicated. RESULTS: A total of 63 patients, 44 with CF (69%) and 85 caregivers (35 mothers, 6 fathers, and 22 mother-father dyads) participated in the study. Caregiver burden was significantly higher in mothers of the CF group with a mean ZCB of 30.5 ± 10.7 when compared to the PCD group with a mean ZCB of 21.93 ± 8.26 (P = .006). This was similar in fathers with mean ZCB of 27.5 ± 9.21 in the CF group and 20.36 ± 7.43 in the PCD group (P = .03). In correlation analyses, mothers' caregiver burden moderately and inversely correlated with CFQOL-R subscales in the CF population. CONCLUSION: Caregiver burden is significantly higher in the CF population when compared to PCD. It is correlated with pulmonary functions and QOL in patients with CF.

Effects of nebulized corticosteroids therapy on hypothalamic-pituitary-adrenal axis in young children with recurrent or persistent wheeze.

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic-pituitary-adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6-24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 microg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.

Nutritional vitamin B12 deficiency in hospitalized young children.

The authors sought to determine prevalence, social, economic, and dietary patterns of young children (n = 20) identified as having vitamin B12 deficiency anemia after admission to their hospital in the last 3 years. The diagnosis of vitamin B12 deficiency was based on symptoms and clinical findings, findings on peripheral blood films and bone marrow aspirates, and serum levels of vitamin B12. The children had been exclusively breast-fed without any animal food supplementation. Serum vitamin B12 levels were also measured in the sera of mothers and found to be low. The authors concluded that vitamin B12 deficiency might be an important health problem among children of mothers who do not consume animal foods adequately.

Evaluation of children with cystic fibrosis by impulse oscillometry when stable and at exacerbation.

BACKGROUND: Pulmonary function tests are important in the diagnosis and follow-up of airway disease in cystic fibrosis (CF). Conventional spirometry for which repeated forced expiration maneuver are needed is considered as the main method. Impulse oscillometry (IOS) is a non-invasive method, which needs minimal cooperation. We performed a prospective cross-sectional study to determine the pulmonary function in CF children with IOS, and evaluate the IOS measurements during acute exacerbation. We hypothesized that IOS can detect lung function impairment in CF patients and detect changes during acute exacerbations. METHODS: CF patients aged 3-18 years were included as the study group and healthy children of the same age formed the control group. The patients were evaluated three times at 3-month intervals. Patients aged >6 years performed both spirometry and IOS while patients aged ≤6 years performed only IOS. In patients with acute exacerbation, spirometry and IOS were performed both at and after the exacerbation. RESULTS: Forty-nine CF patients and 45 healthy children were enrolled to the study. Sixteen patients were admitted with acute exacerbation during the study. The resistance values (R5-10-15-20 Hz) as well as Z5, Fres, and AX values of the patients were higher than those of the control group, while reactance values (X5-10-15-20 Hz) were lower. R values as well as Z5, Fres, and AX values increased during exacerbation and decreased after treatment; X (10-15 Hz) values decreased during exacerbation and increased after recovery (P < 0.05). CONCLUSIONS: IOS may be useful to evaluate pulmonary functions and detect acute exacerbations in CF patients. Pediatr Pulmonol. 2016;51:1151-1158. © 2016 Wiley Periodicals, Inc.