Has the Coronavirus Disease 2019 Pandemic Played a Role in the Early Detection of Pulmonary Embolism in Children?

OBJECTIVE: Pulmonary embolism (PE) poses a significant threat to children, and nonspecific symptoms lead to delayed diagnosis. The emergence of coronavirus disease 2019 (COVID-19) has increased the complexity as it is associated with similar symptoms and increased risk of thrombotic complications. This study aimed to assess the risk factors, clinical presentations, and diagnostic features of PE in pediatric patients and to examine the impact of the COVID-19 pandemic on children with PE. MATERIALS AND METHODS: We conducted a retrospective descriptive study examining the clinical and diagnostic data of 44 pediatric patients with radiologically confirmed PE. The study compared and analyzed patients diagnosed before and during the COVID-19 pandemic. RESULTS: In the study, 21 of 44 pediatric patients were diagnosed in the 4 years before the COVID-19 pandemic, and 23 were diagnosed with PE during the COVID-19 pandemic. The mean time to diagnosis was 8 (2 to 14) days before the pandemic and 1 (1 to 2) days during the pandemic (P < 0.001). The most common associated condition in both groups was infection (65.9%). Dyspnea (65.9%) and tachypnea (50.0%) were common symptoms. Except for deep vein thrombosis, there were no significant differences according to associated conditions between the groups (P = 0.001). Pulmonary emboli were anatomically detected using computed tomography angiography, showing bilateral involvement in 45.4% of patients, segmental artery involvement in 38.6%, and main artery involvement in 15.9%. CONCLUSION: The COVID-19 pandemic heightened suspicion of pediatric PE and accelerated diagnosis. Standardized diagnostic guidelines are increasingly necessary to balance accurate diagnosis with avoiding excessive imaging.

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.

Reversible bronchiectasis caused by influenza virus mimicking Williams-Campbell syndrome.

The term bronchiectasis refers to permanent enlargement of the bronchi. It is increasingly diagnosed because of high-resolution computed investigations. It can be congenital or acquired, the latter mostly following infection. Williams-Campbell syndrome is a rare form of congenital non-cystic fibrosis bronchiectasis. Here we report a 5-month-old girl with reversible bronchiectasis treated with extracorporeal membrane oxygenation for acute respiratory distress syndrome (ARDS) caused by influenza virus following surgery for congenital heart disease. Chest CT showed an abnormally large bronchial tree mimicking Williams-Campbell syndrome. At 9 months later, chest CT showed regression of bronchiectasis and normalized caliber of previously collapsed segments in both lungs. This atypical course illustrates that influenza virus can cause reversible bronchiectasis in infants and mimic congenital disease such as Williams-Campbell syndrome.

Human bocavirus and human metapneumovirus in children with lower respiratory tract infections: Effects on clinical, microbiological features and disease severity .

BACKGROUND: We aimed to compare the clinical findings of human bocavirus (HBoV) and human metapneumovirus (HMPV) infections, and to analyze the effects of coinfections on clinical features and disease severity in children with HBoV and HMPV infections. METHODS: Data were collected from 125 children with lower respiratory tract infections due to HBoV or HMPV, detected from nasal swap by real-time polymerase chain reaction (PCR) during the period from January, 2013 to December, 2017. In total, there were 101 HBoV (group 1) and 23 HMPV (group 2) infections in our data. The patients were further divided into four subgroups according to the coinfection status: HoBV only (subgroup 1, n = 41), HMPV only (subgroup 2, n = 19), HBoV and coinfection with other respiratory viruses (subgroup 3, n = 60), and HMPV and coinfection with other respiratory viruses (subgroup 4, n = 4). RESULTS: The majority (88.8%) of the patients were aged 5 years or younger. Coinfections with other respiratory viruses were significantly more common in group 1 (P = 0.001). Among patients who had nosocomial pneumonia, patients with HBoV infections had significantly longer mean length of hospital stay (LOS) than those with HMPV infections (P = 0.032). The hospitalization and antibiotic requirements were significantly higher in subgroup 1 than subgroup 3 (P = 0.005, 0.039, resp.) According to the logistic regression analyses, the LOS increased by 21.7 times with HBoV infections (P = 0.006). CONCLUSIONS: Human bocavirus and HMPV infections are serious pathogens mostly seen in children and usually requiring hospitalization regardless of co-infection status. The HBoV infections caused longer LOS than the HMPV infections in patients with nosocomial infections.

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.

Evaluation of Allergic Disease Prevalence and Related Risk Factors in Children with Autoimmune Thyroiditis.

BACKGROUND: Allergic and autoimmune diseases are caused by an impaired immunological response resulting from different types of T-helper (Th) cells. Since the Th cell production is in a certain balance, an inverse relationship between the 2 disease groups may exist. In this study, we aimed to investigate the frequency of allergic diseases in children with autoimmune thyroiditis (AT). METHODS: Symptoms of allergic diseases were investigated by the (International Study of Asthma and Allergies in Childhood) ISAAC questionnaire. The questionnaire was administered to a group of 300 children with AT and a control group of 300 children with no known autoimmune disease. The risk factors for allergic diseases and sociodemographic characteristics were investigated. A multivariable logistic regression analysis was performed with the risk factors of allergic diseases. RESULTS: Asthma, wheezing during the last year, wheezing with exercise, disease-free night cough, and night cough were significantly less common in patients with AT. Allergic rhinitis symptoms, except physician-diagnosed allergic rhinitis, are found significantly less frequently in patients with AT. It was found that the presence of AT and an increase in the number of children in the family reduce the risk of allergic diseases; cat-dog contact before 1 year of age and the presence of asthma, eczema, or allergic rhinitis in the mother increase the risk of allergic diseases. CONCLUSIONS: Asthma and allergic rhinitis symptoms were significantly less common in children with AT. AT reduces the risk of allergic diseases.

Evaluation of sleep-disordered breathing and its relationship with respiratory parameters in children with mucopolysaccharidosis Type IVA and VI.

The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = -0.594, p = .009; r = -0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.

Does cystic fibrosis make susceptible to celiac disease?

Patients with cystic fibrosis (CF) have a higher incidence of celiac disease (CD) than the healthy population; however, the actual incidence of coexisting CF and CD is unclear. In this report, we aimed to evaluate the frequency of CD and CF coexistence and to assess the clinical findings of affected patients during follow-up. We conducted a retrospective review of patients with CF to reveal the frequency of CD and also investigated the clinical characteristics and clinical response to gluten-free diet in patients with CD. The incidence of CD in 515 patients with CF was 1.4%. The median age at the time of CF diagnosis was 2 months (1-6 months). CD was diagnosed in six patients with poor weight gain, fatty stools, and low z score for BMI and one patient with poor weight gain despite a high protein and calorie diet and pancreatic enzyme replacement. The median age of CD diagnosis was 8 years (2-12 years). Except for one patient who was recently diagnosed, the other six patients gained weight and their accompanying symptoms resolved after starting a gluten-free diet.Conclusion: CD should be investigated in patients with CF in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. What is Known: • CFTR dysfunction may be a risk factor for CD, due to increased intestinal permeability and intestinal inflammation, pancreatic exocrine insufficiency that results in higher antigen load and increased antibodies against to nutritional antigens such as anti-gliadin IgA antibodies. • Although coexistence of CF and CD are rare in the same patient; there is still no consensus on when children with CF should be screened for CD. What is New: • Physicians should consider the investigation of CD in patients with CF, in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. • CFTR dysfunction has been emphasized to develop susceptibility to CD, and patients with CF who have persistent gastrointestinal symptoms despite appropriate and adequate nutritional and enzyme replacement treatment should be screened for CD.

The frequency and related factors of non-tuberculosis mycobacteria infections among patients with cystic fibrosis.

BACKGROUND: Non-tuberculous mycobacteria (NTM) can cause chronic lung infection particularly in patients who have structural lung disease such as cystic fibrosis (CF). We evaluated the incidence and management of NTM infections in patients with CF in our center. METHODS: A retrospective cohort study was carried out on CF patients having at least one positive NTM isolate between 2012 and 2020. RESULTS: Ten patients (2.1%) had at least one positive NTM culture from respiratory samples. All of them were vaccinated with Bacille Calmette-Guérin (BCG) vaccine, which is in the national vaccination program in our country. Eight patients had the Mycobacterium abscessus complex, one had Mycobacterium avium, and one had Mycobacterium szulgai growth in their respiratory samples. Three patients had transient NTM infection, two had persistent, and five had active NTM infection (NTM pulmonary disease). Patients with NTM pulmonary disease received antibiogram-directed antimycobacterial therapy. In patients with NTM pulmonary disease, the median ppFEV1 and BMI decreased by 17% and 1%, respectively, at the time of the first NTM isolation when compared with the values one year before the first NTM isolation. Culture conversion was not seen in any patient infected with Mycobacteriunm abscessus complex. CONCLUSIONS: The NTM infection incidence is lower in our country than in those countries where the BCG vaccine is not routinely applied. The BCG vaccine may be a protective factor for NTM infection. Further studies are needed about the prevalence of NTM infections, facilitating and protective factors, and appropriate management of NTM infections in patients with CF.

The Effect of Self-Efficacy, Social Support and Quality of Life on Readiness for Transition to Adult Care Among Adolescents with Cystic Fibrosis in Turkey.

PURPOSE: The aim of this study is to examine the effects of self-efficacy, social support and quality of life on readiness for transition to adult care in adolescents with cystic fibrosis. DESIGN AND METHODS: A descriptive and cross-sectional study design was used. Data were collected from 50 adolescent between 14 and 17 years old with cystic fibrosis, by using The Transition Readiness Assessment Questionnaire, Social Support Appraisals Scale for Children, Self-Efficacy Questionnaire for Children and health-related quality-of-life instrument, the KIDSCREEN-10. RESULTS: A positive correlation was found between the readiness levels of adolescents for transition to adult care and self-efficacy levels. In path analysis, self-efficacy was found to have a significant effect on the level of readiness for transition to adult care. There was not statistically significant relationship between the level of readiness for transition to adult care and health-related quality of life and perceived social support. Path analysis revealed that health-related quality of life and perceived social support had significant effects on the self-efficacy levels of adolescents. CONCLUSIONS: Self-efficacy were associated with readiness for the transition to adult care. Although perceived social support and quality of life were not related with transition readiness these variables had significant effects on perceived self-efficacy, which was determined as a factor affecting the readiness for the transition to adult care. PRACTICE IMPLICATIONS: In adolescents with cystic fibrosis, self-efficacy, social support and quality of life levels should be taken into account when planning preparation programs for transition to adult care.

Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis

Background/aim: Cystic fibrosis is an autosomal recessive disease with a defect in mucociliary activity that is characterized by recurrent pulmonary infections. Bacterial agents frequently implicated in airway colonization are Haemophilus influenzae, Staphylococcus spp., and Pseudomonas spp. Fungal isolation from sputum is common in adults. However, growth of fungal agent only in sputum culture in patients with cystic fibrosis is insufficient for the diagnosis of fungal diseases. There is limited data about the clinical significance of fungal isolation in sputum cultures. The aim of the study was to investigate the clinical outcomes andsignificance of fungal isolation from sputum samples in adult CF. Materials and methods: This retrospective study included patients who have been admitted between October 2017 and January 2019 in an adult cystic fibrosis unit. Patients were grouped according to fungal pathogenicity as; fungal disease group, colonization group, and nonisolated group. The data of the last one year, including demographics, clinical data, laboratory, treatment modalities, results of cultured bacteria and fungus from sputum samples, respiratory function parameters, frequency of exacerbation, and hospitalizationwere compared between groups. Results: A total of 330 sputum samples from 88 adult patients with CF were collected. Patients were divided into 3 groups, the fungal disease group (n = 10, 11.4%), colonization group (n = 49, 55.7%), and nonisolated group (n = 29, 32.9%). Presence of pulmonary exacerbation, number of admissions to emergency department, and the number of positive cultures for bacteria from sputum were higher in the fungal disease group (p = 0.03, p = 0.01 and p < 0.001). The fungal disease group had higher rate of antibiotics by parenteral routethan other groups (p = 0.001) whereas lung functions were similar. Use of nutritional supplementation and parenteral antibiotherapy were the factors associated with elevated risk of fungal isolation. Conclusion: Frequent use of parenteral antibiotics and use of nutritional supplementation were found to be independent risk factors for fungal isolation from sputum in adult 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.

Experience with flexible bronchoscopy for noncoronavirus disease of 2019 indications in pediatric patients during the coronavirus disease of 2019 pandemic.

BACKGROUND AND AIM: Flexible bronchoscopy (FB) poses a risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission due to aerosol generation. This study aimed to assess the utilization, indications, outcomes, and safety of FB in pediatric patients for noncoronavirus disease of 2019 (COVID-19) reasons during the pandemic. MATERIALS AND METHODS: We retrospectively analyzed pediatric patients who underwent FB for non-COVID-19 indications at a tertiary children's hospital's pulmonary clinic during the COVID-19 pandemic. Patients showed no COVID-19 symptoms and tested negative for SARS-CoV-2 by real-time polymerase chain reaction (PCR) of nasopharyngeal and throat swabs within 24 h before the procedure. FBs were conducted in the operating room, with healthcare professionals (HCPs) wearing personal protective equipment, including medical N95 masks, gloves, gowns, and eye protection. RESULTS: Between March 2020 and April 2022, 167 pediatric patients underwent FB for non-COVID-19 indications. Common indications included foreign body aspiration (22.7%), stridor (10.1%), and atelectasis (8.9%). No COVID-19 symptoms were observed in patients on the 1st and 10th days post-FB. During the 1-month follow-up, 52 patients underwent SARSCoV-2 PCR testing, and one patient tested positive in the third week after the procedure. None of the HCPs in the FB team experienced COVID-19 symptoms or tested positive for SARS-CoV-2. CONCLUSION: A bronchoscopy protocol with safety precautions minimized the risk of COVID-19 transmission, allowing safe FB performance for non-COVID-19 indications in pediatric patients during the pandemic. The experience gained in FB during COVID-19 is valuable for similar situations in the future.

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.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

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.

Comparison of inhaled mannitol/dornase alfa combination and daily dornase alfa alone in children with cystic fibrosis.

OBJECTIVES: Inhaled recombinant human deoxyribonuclease (dornase alfa) and osmotic agents such as inhaled mannitol are used for improving the clearance of secretions of cystic fibrosis (CF) patients. We aimed to evaluate the long-term clinical effects of adding dry powder inhaled (DPI) mannitol in subjects with CF who are taking daily dornase alfa. METHOD: We conducted a retrospective case-control study on subjects with CF. The effect of DPI mannitol was assessed by comparing DPI mannitol and dornase alfa combination with daily dornase alfa alone in children with CF during a 12-month period. The primary outcome measures of the study were absolute changes in percent predicted forced expiratory volume in 1 s (FEV1) and FEV1 z-scores and the secondary outcomes included other spirometry indices, body mass index, frequency of pulmonary exacerbations, SPO2 , and sputum microbiology. RESULT: Of a total of 28 patients who committed to use DPI mannitol treatments during the study period, five had a positive challenge with DPI mannitol and two were aged over 18 years. Therefore, the mannitol treatment group consisted of 21 patients. However, the effect of DPI mannitol was analyzed using 15 patients in the mannitol treatment group who received DPI mannitol for at least 12 months, and 18 patients who only used dornase alfa constituted the control group. The median absolute change in FEV1 between baseline and the third month; and baseline and the 12th month were significantly higher in the mannitol treatment group (p = 0.038, p = 0.004, respectively). When the groups are compared with respect to absolute z-score changes, all spirometry indices, except FVC at the end of 3 months, showed statistically significant improvements in the mannitol treatment group. Some secondary outcomes like pulmonary exacerbation frequency during the study year and median absolute body mass index z-score changes from baseline to the end of the study showed no significant differences between the groups (p = 0.735, p = 0.161, respectively). No colonization changes were observed in the treatment group. CONCLUSIONS: This study showed that in those patients who tolerated long-term (12 months) treatment with DPI mannitol and dornase alfa made greater improvements in FEV1, FVC, FEV1/FVC, FEF25-75 z-scores than treatment with dornase alfa alone in children with CF.

Clinical radiological and pathological staging of children with hypersensitivity pneumonitis.

OBJECTIVE: Hypersensitivity pneumonitis (HP) is rare in the pediatric population. To date, there are no studies defining a correlation between clinical, radiological, and pathological findings in children with HP. The objective of this study is to define the clinical, and radiological characteristics and prognosis of childhood HP and to examine the clinical, radiological, and pathological correlation between HP stages. METHODS: Patients with suspected HP and followed at two tertiary care hospitals between 2000 and 2020 were retrospectively evaluated. Computed tomography (CT) of the chest of patients was evaluated by a single radiologist. The interagreement between clinical and radiological severity of the patients was calculated with the κ test. RESULTS: Fourteen children with suspected HP were identified. The results of 10 patients with the definitive diagnosis were as follows: one patient (10%) had acute, five patients (50%) had subacute, and four patients (40%) had chronic HP. The most prominent findings in chest CT were hilar, or hilar and subcarinal lymphadenopathy (80%), centrilobular nodules (60%), patchy or diffuse ground-glass opacities (50%), and cysts (50%). The interagreement between clinical and radiological severity of the patients was 100% (approximate significance: 0.003). The diagnosis of four patients with suspected HP who were unresponsive to standardized medical treatments or developed multisystem involvement was diagnosed with other diseases. One patient (10%) with definitive chronic HP died due to respiratory failure during follow up. CONCLUSION: Similar to adult HP, the prognosis is worse in children with existing fibrotic equivalents in chest CT. Patients who are not responding to standard medical treatments or develop multisystem involvement should be evaluated for other lung diseases.

Antimycobacterial prophylaxis regarding Bacillus Calmette-Guérin -associated complications in children with primary immunodeficiency.

OBJECTIVE: Bacillus Calmette-Guérin (BCG) vaccine derived from Mycobacterium bovis can cause BCG vaccine associated complications (BCG-VAC) especially in patients with primary immunodeficiencies (PID). No consensus exists for antimycobacterial prophylactic therapy for patients with PID who receive the BCG vaccine. AIM: This study aimed to define the risk factors in the development of BCG-VAC and effect of antimycobacterial prophylaxis in PID patients vaccinated with BCG. METHODS: This is a retrospective cohort study. 104 patients diagnosed with PID who received the BCG vaccination were referred to pediatric pulmonology in a single center were enrolled. The demographic characteristics, type, dosage and duration of antimycobacterial prophylaxis regimen, treatment modalities for BCG-VAC were documented. Regression analysis was performed to evaluate the effect of covariates for predicting BCG-VAC in patients with PIDs. RESULTS: Among 104 patients 21 (21.2%) developed BCG-VAC. The frequency of BCG-VAC was highest in patients with Mendelian susceptibility to mycobacterial disease (46.2%) followed by patients with severe combined immunodeficiency (22.4%) and those with chronic granulomatous disease (9.5%). Prophylactic therapy against mycobacterium was initiated for 72 patients (69.2%). Among patients who received the antimycobacterial prophylaxis, BCG-VAC developed in only four patients (5.6%), whereas 17 patients (53.1%) developed BCG-VAC in the non-prophylaxis group and this difference was statistically significant (p < 0.001). Multivariable regression analysis with age at diagnosis, type of PID, receiving antimycobacterial prophylaxis, median T cell number at the time of PID diagnosis and HSCT status showed that not receiving antimycobacterial prophylaxis and lower median T cell number were predictors, with antimycobacterial prophylaxis having the highest odds ratio for BCG-VAC prediction in patients with PIDs (p:<0.001, R2:0.64). CONCLUSION: The lower frequency of BCG-VAC in our cohort can be explained by two main reasons; relatively late BCG vaccination schedule and receiving antimycobacterial prophylaxis. It is reasonable to begin antimycobacterial prophylaxis in patients with PIDs who are susceptible to BCG-VAC.

Impact of Achromobacter spp. isolation on clinical outcomes in children with cystic fibrosis.

BACKGROUND: The prevalence of Achromobacter spp. in cystic fibrosis (CF) has increased while its significance remains controversial. Our aim was to investigate the impact of Achromobacter spp. isolation on clinical outcomes in children with CF. METHODS: Children with Achromobacter spp. isolation were retrospectively included from the CF database of our center. Control groups of children with CF, who had never been infected by Achromobacter spp., were individually case-matched by age, sex, and Pseudomonas aeruginosa isolation status. Pulmonary function and exacerbation frequency were compared between groups during follow-up. RESULTS: Thirty-seven children had at least one respiratory specimen positive for Achromobacter spp. Achromobacter spp. were chronically isolated from 15 (40.5%) and intermittently from 22 (59.5%) of these 37 children. Although the baseline forced expiratory volume in 1 s (FEV1) z-score was similar between the Achromobacter spp.-infected and -uninfected groups (-0.65 ± 2.22 vs. -0.15 ± 1.30, respectively; p = 0.318), children infected by Achromobacter spp. had a lower FEV1 z-score compared to the control group by the end of the first year (-1.37 ± 2.17 vs. -0.14 ± 1.65, respectively; p = 0.025). In addition, the FEV1 decline in 1 year was significantly greater in the group infected by Achromobacter spp. compared to the uninfected group (-1.18%/year vs. -9.07%/year, respectively; p = 0.043). Furthermore, the cumulative numbers of exacerbations observed in the Achromobacter spp.-infected group were higher compared to the control group by the end of the second year (4 [0-17] versus 3 [0-9], respectively; p = 0.001). CONCLUSIONS: Achromobacter spp. isolation is associated with more accelerated decline in lung function parameters and frequent exacerbations in children with CF.