The Coronavirus Disease 2019 Pandemic and Time to Diagnosis for Childhood Pulmonary Diseases: Outcomes of a Tertiary Care Center.

Coronavirus disease 2019 pandemic caused many changes in the social behaviors of individuals and the provision of health systems. Many studies revealed reductions in the number of diagnoses and delays in diagnosis time during the pandemic. This study aimed to evaluate the effect of the pandemic on the time to diagnosis of major diseases of pediatric pulmonology. Newly diagnosed patients with cystic fibrosis (CF), childhood interstitial lung disease (chILD), tuberculosis (TB), and primary ciliary dyskinesia (PCD) were grouped into pandemic (group 1) and 2 consecutive pre-pandemic periods divided into equal intervals (groups 2 and 3). For each disease group, the time to diagnosis was compared between the specified periods. A total number of patients were 171 in this study. In the CF group, there was no statistically difference in time to diagnosis between periods. In the chILD group, there was a statistically significant difference in time to diagnosis (P = .036) between groups (group 1: 2 months, group 2: 4 months and group 3: 10.5 months) that was not originated from pandemic period. In TB group there was no statistically significant difference between groups. In the PCD group, the impact of the pandemic on the time to diagnosis could not be clarified because the time interval to diagnosis (minimum: 2 years, maximum: 16 years) exceeded the studied periods (21 months). In our study, no effect found between the pandemic and age at diagnosis or time to diagnosis in patients with PCD, chILD, CF, and TB at our center.

Exercise intolerance, oxidative stress, and irisin in pediatric cystic fibrosis: Can telehealth-based exercise training make a difference?

BACKGROUND: Patients with cystic fibrosis (CF) experience increased oxidative stress. Tele-exercise can be a new method to improve exercise in CF. OBJECTIVE: This study aimed to investigate the effect of telehealth-based exercise training using different modalities (combined exercise training group, CombG, core stabilization exercise group, SG), in comparison with control group (CG), on exercise capacity, oxidative stress, and irisin in children with CF. METHODS: Thirty-nine children with CF (mean age=11.41±2.18 years, mean FEV1(z-score)=-0.66±1.96) were included in the study. The children were randomly allocated to groups. The CombG and SG performed core stabilization exercises (CS) 3 days per week for 8 weeks. The CombG also performed aerobic exercises 3 days per week in addition to CS. Physical activity (PA) recommendations were provided to the CG. Exercise capacity was evaluated using the Modified Shuttle Test (MST). Oxidative stress was assessed using total antioxidant status (TAS), total oxidant status (TOS), Oxidative Stress Index (OSI), malondialdehyde (MDA), and superoxide dismutase (SOD). The irisin level was also measured. RESULTS: Children's baseline sex, age, BMI, and FEV1 z-scores were similar (p > 0.05). The MST distance (p = 0.047,np2=0.157) and%MST distance (p = 0.045, np2=0.159) significantly improved in the CombG compared with the SG and CG. Although TAS and SOD decreased over time (p < 0.05), no significant changes were observed for TAS, TOS, OSI, MDA, SOD, and irisin parameters between the groups after training (p > 0.05). CONCLUSIONS: Combining aerobic exercise training with core stabilization applied using telehealth improved exercise capacity more than core stabilitation training only or PA recommendations in children with CF.

Evaluation of otorhinolaryngologic, audiologic, and genetic findings in children with cystic fibrosis: A tertiary care experience.

OBJECTIVES: To evaluate otorhinolaryngologic findings and the relationship between aminoglycoside (AG) exposure and hearing loss in paediatric patients with cystic fibrosis (cwCF). We also aimed to investigate the genetic predisposition to AG ototoxicity by screening for m.1555A>G mutations. METHODS: CwCF who underwent otorhinolaryngologic and audiologic examinations were retrospectively included. Clinical characteristics, ear-nose-throat related symptoms, and a history of ototoxic drug exposure were recorded. m.1555A>G mutations were retrospectively screened among patients with audiologic evaluations. RESULTS: Two hundred thirty-four cwCF were included in this study with a median age of 10.7 (range, 6.8-14.2) years. Nasal obstruction (14.1%) was the most common symptom. Fifty-two (22.2%) patients had chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). There was a positive correlation between CRSwNP and the symptom of nasal obstruction (r:.234, p < .001), snoring (r:.179, p = .006), and sleeping with mouth open (r:.138, p = .034). One hundred forty-nine (63.6%) patients had audiologic evaluations; 14 (9.4%) had hearing impairment. No statistical significance existed between ototoxicity and IV AG exposure (p = .90). Six (42.8%) of 14 patients did not receive ototoxic drugs. One hundred nineteen (50.8%) patients were screened for m.1555A>G mutations, and none were detected. CONCLUSIONS: Almost a quarter of the study population had CRSwNP. Neither the relationship between AGs exposure and hearing loss nor the genetic predisposition to AG ototoxicity could be shown in cwCF.

Impact of interruption of CFTR modulator therapies.

Novel drug therapy targeting the defective cystic fibrosis transmembrane conductance regulator protein has the potential to significantly enhance the quality of life for numerous patients with cystic fibrosis. However, in some countries social insurance does not pay for modulators because these drugs are extremely expensive. This study sought to understand the impact on the health of children whose modulator treatments were interrupted because of legal procedures and delivery processes. Our study identified that the significant increase in percent-predicted forced expiratory volume levels (FEV1) and BMI z-score values associated with modulator therapies decreased sharply with their discontinuation. Significant worsening in FEV1, BMI z-scores, and BW z-scores were detected in the first follow-up visit after therapy discontinuation within 1 month. Eight patients had a reduction of FEV1 of more than 10%. The findings suggest that modulatory treatment continuation is important, and it is crucial that treatment is not interrupted.

Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006).   Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

The airway microbiota in siblings with primary ciliary dyskinesia: Related factors and correlation with clinical characteristics.

OBJECTIVES-AIM: We aimed to show the composition and structure of and explore affecting factors on airway microbiota in primary ciliary dyskinesia (PCD) patients using culture-independent techniques. METHOD: A cross-sectional observational study was performed. We recruited 14 PCD patients (seven pairs of siblings) and nine parents. Bacterial rDNA was extracted from sputum and nasal samples. Sputum samples were also inoculated on suitable bacteriological media. RESULTS: Thirty-three separate genera were detected in sputum samples of PCD patients, and 41 were in nasal samples of parents. The detected genera were dominated by phyla Proteobacteria in PCD patients and their parents. Culture-dependent analyses could not detect many of the bacterial species detected with culture-independent analyses. There were no significant differences in alpha diversity between the siblings' pairs, and siblings' samples did not cluster together nearly as strongly as nonsiblings' samples. Patients who had no new complaints and no bacterial growth with the culture-dependent method at the time of study and patients who had no Haemophilus influenzae growth in the previous year had a significantly greater diversity (p < .05). Microbiota communities tended to cluster together by age, pulmonary exacerbation status, the existence of at least one H. influenzae growth with culture-dependent analyses in the previous year, and forced expiratory volume in 1 sec z and FEF25-75 z-scores. CONCLUSION: The airway microbiota of patients with PCD have presented more diverse bacterial communities than had been indicated with culture-dependent methods. The study identifies relationships between bacterial airway microbiota composition and the clinical measures of patients. Sibling pairs have no more community similarities than nonsibling PCD patients. Our results may indicate that the patients' clinical characteristics, which determine the disease severity, might affect the PCD microbiome.

Cystic fibrosis related bone disease in children: Can it be predicted?

BACKGROUND&AIMS: Cystic fibrosis (CF) -related bone disease (CFBD) is an important complication of CF, and low BMD in childhood is a precursor of CFBD. Here, we aimed to investigate bone turnover biomarkers, including osteocalcin (OC), receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in relation to low BMD in children with CF (cwCF). We also evaluated factors which could affect bone turnover with particular emphasis on fat-free mass (FFM), forced expiratory volume in 1 s (FEV1), hand grip strength (HGS), and functional capacity and physical activity. METHODS: Sixteen cwCF aged 8-18 years with moderate low BMD (group1) and 64 cwCF with normal BMD (group2) were enrolled. Serum RANKL, OC, and OPG were determined by immunoenzymatic assays. Multiple parameters including pancreatic status, lung functions, body mass index (BMI), FFM measured by bioelectric impedance analysis (BIA), 6-minute walk test, vitamin D, nutritional intake, HGS, functional capacity and physical activity, serum and urine biomarkers were compared between the two groups. RESULTS: We found similar serum levels of RANKL (p = 0.501), OC (p = 0.445), OPG (p = 0.380), and RANKL/OPG ratio (p = 0.449) between group1 and group2 in cwCF. BMI z-score (p < 0.001), FFMI z-score (p < 0.001), FEV1 z-score (p = 0.007), and right-HGS (%pred) (p = 0.009) significantly differed between the two groups. Multivariate linear regression revealed that the only factors that predicted BMD were FFMI z-score and HGS %pred. CONCLUSION: Serum OC, OPG, RANKL and RANKL/OPG ratio did not predict BMD in cwCF. FFMI z-score and HGS %pred measured by non-invasive and practical methods were the best predictors of BMD.

Plastic bronchitis during childhood: Diversity of presentation, etiology, treatment, and outcomes.

OBJECTIVE: Plastic bronchitis (PB) is a rare disease in children, and reliable data are scarce. Here, we aimed to analyze the clinical features, management, and outcomes in children with PB. METHODS: The medical data of patients who were followed up with a diagnosis of PB between January 2010 and March 2022 were retrospectively analyzed. RESULTS: The median age of 15 patients was 9 (interquartile range: 4-10) years with a male/female ratio of 12/3. Initial symptoms included recurrent pneumonia (33.3%), persistent atelectasis (33.3%), cast expectoration (26.6%), and intense, persistent cough (6.6%). The most common underlying diagnosis was asthma (n = 12, 80%), and six of the patients were newly diagnosed. The most common radiological findings were atelectasis as a consequence of major airway obstruction on chest X-ray or computed tomography. Five patients, all diagnosed as having asthma, had recurrent PB and required multiple airway procedures for treatment and diagnosis. During a median 7-year follow-up of five patients, occasionally cast expectoration was observed in one patient with asthma who had poor compliance with inhaled corticosteroids. CONCLUSION: PB is a common reflection of the different underlying etiologies in the pediatric age group, and treatment and outcomes are closely related to these. It should be kept in mind that asthma can be a predisposing factor for the development of PB.

Evaluation of polysomnography findings in children with genetic skeletal disorders.

Children with genetic skeletal disorders have variable conditions that can lead to sleep-disordered breathing, and polysomnography is the gold standard for diagnosing this condition. We aimed to review polysomnography findings, to assess the severity of sleep apnea, and to investigate the clinical variables predictive of sleep-disordered breathing in these patients. We retrospectively collected the medical records of patients with genetic skeletal disorders who underwent polysomnography for 5 years. Twenty-seven children with various genetic skeletal disorders, including achondroplasia (14), Crouzon syndrome (3), acromesomelic dysplasia Maroteaux type (3), Apert syndrome (2), osteopetrosis (1), Jeune dysplasia (1), Desbuquois dysplasia (1), acrodysostosis (1), and spondyloepiphyseal dysplasia (1) were enrolled. The median age at the first polysomnography was 58 (1st-3rd quartile: 31-113) months. The overall sleep-disordered breathing results were: 19 (70.3%) had obstructive sleep apneas (OSA) (4 mild, 6 moderate, 9 severe), 2 (7.4%) had central apneas, 4 (14.8%) had nocturnal hypoventilation. There was a significant correlation between non-ambulatory status with both total AHI and OSA (p < 0.001, rho: -0.66/p = 0.04, rho: 0.38, respectively). Nine patients received positive airway pressure titration, and the oAHI values of all returned to the normal range. These patients were started with positive airway pressure treatment. Our cohort showed that the majority of the patients with skeletal dysplasia had sleep apnea syndrome characterised mainly by OSA, highlighting the importance of polysomnography screening for sleep disorders. Positive airway pressure therapy represents an effective treatment for sleep-disordered breathing in those patients.

A case-control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis.

INTRODUCTION: There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively. METHODS: Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up. RESULTS: Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar. CONCLUSION: Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

Evaluation of Clinical Findings in Children with Chylothorax: A Descriptive Study.

OBJECTIVE: Chylothorax refers to the presence of chyle in the pleural space. There are multiple etiologies of chylothorax. Our aim in this study was to evaluate the clinical manifestations, causes, and treatment of chylothorax in childhood and also to show the differences between the 2 age groups admitted to a tertiary care children's hospital. The second aim was to evaluate the clinical and radiologic features of patients diagnosed as having Gorham-Stout disease via chylothorax. MATERIALS AND METHODS: The archives were reviewed for chylothorax documented in the last 31 years. Twenty-two patients (11 girls and 11 boys) were included. Patients were divided into 2 groups: the younger group aged under 24 months and the older group aged over 24 months. RESULTS: A total of 22 patients had chylothorax, and 10 were aged younger than 24 months. In the younger group, etiologies were in order congenital heart surgery, congenital chylothorax, and Gorham-Stout disease. In the older group, etiologies were Gorham-Stout disease, congenital heart surgery, heart failure, heart transplantation, thrombus, intestinal lymphangiectasia, and idiopathic. The most common treatment in the younger group was the medium-chain triglyceride diet (70%), and in the older group, it was sirolimus (50%). CONCLUSION: There is a wide variety of underlying etiologies in childhood, so a multidisciplinary approach is important to identify the underlying diagnosis. The common etiologies were postoperative and Gorham-Stout disease in our study. All patients with Gorham-Stout disease had a good prognosis. Gorham-Stout disease should be considered in patients of any age with a diagnosis of chylothorax who have bone lesions.

The effect of Pseudomonas aeruginosa eradication regimens on chronic colonization and clinical outcomes in pediatric patients with cystic fibrosis.

BACKGROUND: Chronic Pseudomonas aeruginosa colonization (Pa-CC) affects cystic fibrosis (CF) progression, including pulmonary exacerbations and pulmonary function tests. There are few studies of the effects of eradication protocols on colonization time. Here, we aimed to evaluate the effect of eradication regimens on chronic colonization and assess the impact of Pa-CC on body mass index, lung functions, and pulmonary exacerbations. METHODS: A retrospective review was conducted of medical records, over a period of 11 years, of children aged under 18 years with CF who had Pa-CC in our tertiary care pediatric hospital. RESULTS: Pseudomonas aeruginosa was detected in 215 of our patients with CF during the study period. Forty-four patients with Pa-CC were recruited for the study. The eradication treatment for the initial acquisition of P. aeruginosa was inhaled antibiotics in 27 (61.4%) patients; the remainder were given intravenous antibiotics. It was observed that eradication treatment with either IV or inhaled antibiotics did not affect the time between the P. aeruginosa and the time of Pa-CC(P = 0.791). There was a non-significant decrease in the body mass index z-score from the Pa-IA to the last visit(P = 0.27), a significant decline in forced expiratory volume in 1 s (FEV1%) (P = 0.01) over time, and the annual number of exacerbations after colonization was significantly higher than before colonization (P = 0.03). CONCLUSIONS: There was no difference between eradication regimens in delaying the age at Pa-CC. Pseudomonas aeruginosa colonization in patients with CF was also associated with poorer lung functions, lower body mass index, and more pulmonary exacerbation regardless of mucoid type. Consequently, to slow the progression of lung disease, we must prevent Pa-CC, which we can achieve with early eradication. Despite conventional eradication protocols, future studies need to evaluate those who fail to clear P. aeruginosa.

Clinical findings of methicillin-resistant Staphylococcus aureus in cystic fibrosis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) rates have increased in cystic fibrosis (CF) patients.This study aimed to determine the rate of MRSA, define risk factors, and clarify the effect of MRSA on pulmonary functions, annual pulmonary exacerbation (aPEx) in children with MRSA positive CF. METHODS: This was a retrospective case control study. CF patients who had ≥1 MRSA (+) respiratory culture between September 2016-2019 were included. MRSA growth rate, colonization status, clinical characteristics, hospitalization rates, FEV1 %predicted, and z-score one year prior to the MRSA isolation, at MRSA growth and one year after MRSA growth were recorded. The aPEx rate changes before-after MRSA growth were evaluated. RESULTS: Sixty-one subjects who had ≥1MRSA growth and 66 controls were enrolled. There was no statistically significant difference between the spirometry indices at first, and 12th month after MRSA acquisition. The mean aPEx was 0.6 one year prior to MRSA acquisition and this rate significantly increased to 1.2 one year after MRSA growth(p < 0.05). The mean hospitalization rate before and after one year of MRSA acquisition significantly increased from 0.17(±0.12) to 0.48 (±0.3)(p:0.008) admissions per year. CONCLUSIONS: MRSA growth was related to increased aPEx. Increased aPEx and hospitalization rates after MRSA acquisition suggest MRSA should be eradicated when detected.

Association between early chronic methicillin-susceptible Staphylococcus aureus colonization and lung function in children with cystic fibrosis.

BACKGROUND: Our aim was to determine whether early chronic methicillin-susceptible Staphylococcus aureus (MSSA) colonization in children with cystic fibrosis (CF) is associated at 8 years of age with poorer lung function, poorer nutritional status, and increased exacerbation frequency. METHODS: In this retrospective cohort study, a total of 52 children with chronic MSSA colonization were included. Of them, 26 were chronically colonized with MSSA before the age of 4 years (early onset), and 26 were chronically colonized from 4 years to 6 years of age (late-onset). At the age of 8 years, lung function, body mass index (BMI) as an indicator of nutritional status and frequency of pulmonary exacerbations were compared between two groups. RESULTS: At 8 years of age, BMI was similar between the early-onset and late-onset groups (15.0 [min-max: 12.9-26.8] vs. 15.7 (min-max: 13.0-24.9), p = 0.327]. Percentage of forced expiratory volume in 1 s (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) in 8-year-old children were significantly lower in the early onset group compared to the late-onset group (98 [min-max: 44-139] vs. 106.5 [min-max: 82-131], p = 0.047; 84.9 ± 25.5 vs. -102.3 ± 26.3, respectively; p = 0.019], although the percentage of forced vital capacity did not differ significantly between two groups (93.5 [min-max: 45-131] vs. 103 [min-max: 84-119], respectively; p = 0.092). Exacerbation frequency between the ages of 6 and 8 years in the early onset group was higher compared to the late-onset group according to the Poisson regression model [1 (min-max:0-10) vs 0 (min-max:0-4), respectively; p = 0.044]. CONCLUSIONS: Early chronic MSSA colonization is associated with poorer lung function and frequent exacerbations in children with CF. However, further studies are needed to reveal the cause-and-effect relationship between early chronic MSSA colonization and pulmonary outcome.

The Importance of Flexible Bronchoscopy in Difficult-to-treat Asthma from a Pediatric Pulmonology Perspective.

OBJECTIVE: Asthma is the most common chronic lung disease in childhood. Difficult-to-treat asthma is defined as the continuation of symptoms or attacks of patients despite step 4 or 5 of Global Initiative for Asthma therapy. In the differential diagnosis of these patients, flexible fiberoptic bronchoscopy is recommended to exclude other lung diseases. In this study, we aimed to examine the clinical and radiologic features and flexible fiberoptic bronchoscopy findings of patients referred to our pediatric pulmonology department due to difficult-to-treat asthma and determine the effects of flexible fiberoptic bronchoscopy on the differential diagnosis and treatment. MATERIALS AND METHODS: The demographic characteristics and flexible fiberoptic bronchoscopy results of 62 patients who were diagnosed as having difficult-to-treat asthma in our pediatric pulmonology department between January 2015 and June 2020 were evaluated retrospectively. The symptoms, history, medications, physical examination findings, pulmonary function tests, and radiologic findings of patients who underwent flexible fiberoptic bronchoscopy were evaluated. RESULTS: The median age of the patients was 69 (interquartile range: 42-108 months). The most common reasons for the referral of these patients were chronic cough, recurrent pulmonary infections, and persistent wheezing. All patients had chest radiography and 37 (59.7%) had chest computed tomography at their first admission; 14 (37.8%) patients had abnormal findings on chest computed tomography. There was no significant difference in terms of age, physical examination findings, pulmonary function test results, and radiologic examinations between patients with and without pathologic bronchoscopy findings. None of the patients had complications during and after flexible fiberoptic bronchoscopy. The most common diagnoses of patients based on flexible fiberoptic bronchoscopy were persistent bacterial bronchitis in 19 (30.6%) patients, tracheomalacia and/or bronchomalacia in 12 (19.4%), and anatomic anomalies in 3 (4.8%) patients (separation of lingula into 3, separation of right upper lobe bronchus into 4, and tracheal dyskinesia). Mycobacterium tuberculosis growth was observed in the tuberculosis culture of 1 patient. According to the flexible fiberoptic bronchoscopy and bronchoalveolar lavage results, antituberculosis treatment was initiated in 1 patient and polypoid mass excision was performed in 1 patient. A proton pump inhibitor was started in 9 (15.5%) patients, physiotherapy in 5 (8.0%), antibiotics in 14 (22.5%), and ipratropium bromide in 7 (11.2%) patients. All patients were followed up with the diagnosis of asthma except for 2 patients. CONCLUSION: To date, there is no prospective study evaluating the importance of flexible fiberoptic bronchoscopy in difficult-to-treat asthma in childhood. In our small cohort, persistent bacterial bronchitis, airway tracheomalacia and/or bronchomalacia, gastroesophageal reflux, and other anatomic anomalies were successfully diagnosed using flexible fiberoptic bronchoscopy and treated without any complications, suggesting that flexible fiberoptic bronchoscopy is an important diagnostic tool with a low complication rate in children with difficult-to-treat asthma.