Tamara Svobodová

Dose‐related efficacy and safety of formoterol (Oxis®) Turbuhaler® compared with salmeterol Diskhaler® in children with asthma

To compare the dose‐related bronchodilator efficacy and tolerability of formoterol (Oxis®) Turbuhaler® with salmeterol Diskhaler® and placebo in children with asthma. A single‐dose, randomized, double‐blind, incomplete crossover study of 68 children (7–17 years), with moderate‐to‐severe asthma, 82% receiving inhaled corticosteroids. Patients received four of six treatments [4.5, 9, 18, or 36 μg formoterol (6, 12, 24 or 48 μg metered doses), 50 μg salmeterol (metered dose) or placebo] at 12‐h visits, separated by ≥3 days. Forced expiratory volume in 1 s (FEV1), pulse, blood pressure, electrocardiogram, adverse events and urine formoterol were assessed. The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results. All active treatments significantly improved FEV1 compared with placebo. Formoterol 9–36 μg provided dose‐related increases over salmeterol in lung function: average 12‐h FEV1 (increases of 4.9–8.7%, p < 0.001) and FEV1 at 12 h post‐dose (7.0–12.2%, p < 0.001). The onset of effect of formoterol was also significantly faster than salmeterol for doses ≥9 μg. Salmeterol 50 μg was estimated to be equieffective to 3.3 μg formoterol for 12‐h average FEV1 and the estimated equieffective dose for a variety of systemic effects was 7.8–13.5 μg formoterol. All treatments were well tolerated. Formoterol (Oxis) Turbuhaler 4.5–36 μg provided dose‐related improvements in bronchodilator efficacy in children with asthma. Formoterol ≥9 μg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 μg with no increase in systemic effects.

Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetically heterogenous condition. Mutations in DNAH5 or DNAI1 genes can be found in about a third of the patients with PCD. Increased occurrence of mutations was described in several exons of these long genes. The objective of the study was to test the sensitivity of sequencing of selected 13 exons (as compared to costly sequencing of all 100 exons of the two genes), and to determine the prevalence of the DNAH5 or DNAI1 mutations in the Czech PCD database.

An effective combination of sanger and next generation sequencing in diagnostics of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a multigenic autosomal recessive condition affecting respiratory tract and other organs where ciliary motility is required. The extent of its genetic heterogeneity is remarkable. The aim of the study was to develop a cost‐effective pipeline for genetic diagnostics using a combination of Sanger and next generation sequencing (NGS).

Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood

BackgroundGATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease.Case presentationWe present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient’s pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient’s brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen.ConclusionWe conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient’s family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.

Impaired Growth during Childhood in Patients with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) leads to recurrent/chronic respiratory infections, resulting in chronic inflammation and potentially in chronic pulmonary disease with bronchiectasis. We analyzed longitudinal data on body length/height and body mass index (BMI) for 29 children and young adults with PCD aging 1.5–24 years (median, 14.5) who had been diagnosed at the age of 0.5–17 years (median, 8). Of these, 10 carried pathogenic mutations in either DNAH5 or DNAI1. In children with PCD, body length/height progressively decreased from +0.40 ± 0.24 SDS (the 1st birthday), +0.16 ± 0.23 SDS (3 years old), and −0.13 ± 0.21 SDS (5 years old) to −0.54 ± 0.19 SDS (7 years old; P = 0.01 versus 0), −0.67 ± 0.21 SDS (9 years old; P = 0.005 versus 0), −0.52 ± 0.24 SDS (11 years old; P = 0.04 versus 0), and −0.53 ± 0.23 SDS (13 years old; P = 0.03 versus 0). These results reflect low growth rates during the childhood growth period. Thereafter, heights stabilized up to the age of 17 years. The growth deterioration was not dependent on sex or disease severity but was more pronounced in DNAH5 or DNAI1 mutation carriers. BMI did not differ from population standards, which suggests that nutritional deficits are not the cause of growth delay. We conclude that PCD leads to chronic deprivation with significant growth deterioration during childhood.

Epithelial basement membrane thickening is related to TGF-Beta 1 expression in children with chronic respiratory diseases

The complex structural changes of bronchial mucosa, known as remodelling, have been considered unique and typical for asthma. However, similar changes were recently found in other chronic respiratory diseases. The aim of this study was to compare basement membrane (BM) thickness and the number of transforming growth factor beta 1 (TGF‐β1) positive epithelial cells in children with asthma, cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and healthy controls.

Abnormalities in pulmonary function in infants with high-risk congenital diaphragmatic hernia

AIMS The aim of the study was to analyze lung growth and abnormality of infant pulmonary function tests (IPFT) in congenital diaphragmatic hernia (CDH) survivors younger than three years of age with respect to unfavorable prognostic factors. METHODS Thirty high-risk CDH survivors at the age of 1.32±0.54 years, body weight 9.76±1.25 kg were examined using IPFT: tidal breathing analysis, baby resistance/compliance, whole baby body plethysmography and rapid thoraco-abdominal compression. Gore-Tex patch was used in 13% of patients (GORE group). Pulmonary hypertension was diagnosed and managed in 13% (iNO group). Standard protocols and appropriate reference values were used and obtained data were statistically analysed. RESULTS High incidence of peripheral airway obstruction (70%), increased value of functional residual capacity (FRCp) 191.3±24.5 mL (126.5±36.9 % predicted; P < 0.0005), increased value of effective airway resistance (Reff) 1.71±0.93 kPa.L(-1).s (144.4±80.1 % predicted; P < 0.01) and decreased specific compliance of the respiratory system (Crs/kg) 14.1±2.3 mL.kPa.kg(-1) (i.e., 76.1±20.1 % predicted, P < 0.0005) was noted in infants with CDH in comparison with reference values. Increased value of FRCp was found in GORE group (165.7±51.9 versus 120.4±31.2, P < 0.02) and in iNO group (183.1±52.6 versus 117.8±25.7 mL; P < 0.0005). CONCLUSION A high incidence of peripheral airway obstruction, an increased value of FRCp and decreased specific compliance of the respiratory system was noted in infants with CDH. Unfavorable prognostic factors (Gore-Tex patch, pulmonary hypertension) correlate with more severe alteration of pulmonary function in infants.

Tracheal diverticulum with decompensation after 8 years of conservative therapy requiring surgical solution

Tracheal diverticulum is a benign cystic mass in the cervical and mediastinal regions, with an incidence of 1% in post‐mortem findings, and 2% in CT findings. The lesion is in most cases completely asymptomatic and is most commonly incidentally detected during a CT examination. We present the case of a young female patient with a tracheal diverticulum who has been followed up for 8 years by pediatric pneumologist. Patient health state deteriorated and she developed stress‐induced dyspnea requiring surgical resection. Moreover, we mention differential diagnosis of other mediastinal cystic lesions. Pediatr Pulmonol. 2015; 50:E44–E47.

Pitfalls in Pediatric Bronchoscopy

Bronchoscopy has traditionally been an integral part of pulmonary diagnostics and therapy. In pediatrics, bronchoscopy was originally mainly used for the extraction of aspirated foreign bodies or other interventions, less frequently for diagnostic procedures. Since the introduction of pediatric flexible instruments, bronchoscopy has become more available and has been used much more often in pediatric pulmonary medicine. With the current general availability of the method, it is essential to make sure that bronchoscopes are used according to accepted standards. This article reviews some of the potential pitfalls in performing and interpreting pediatric bronchoscopy.