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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.

Summary Background 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). Materials and Methods Data and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation. Results The causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi-allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre-screening step, being followed by an NGS panel for other, much larger, PCD genes. Conclusions We present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate-size national collection of patients. This strategy has proven to be cost-effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

Nitrogen multiple breath washout test is a safe, feasible and repeatable method for infants with cystic fibrosis. It may outperform sulphur hexafluoride variant with respect to its better suitability for long time follow up and lower technical demands

Introduction: Omalizumab is indicated for the treatment of severe allergic bronchial asthma and chronic spontaneous urticaria, although number of studies confirmed the efficacy of this therapy also on other IgE-mediated diseases. The aim of this study was to assess the impact of anti-IgE therapy on comorbid allergic diseases in patients treated with omalizumab for severe allergic asthma. Methods: In the study there were enrolled 310 patients with severe asthma treated with omalizumab between 2006–2015 in specialized centers for severe asthma treatment in the Czech Republic. The effect on clinical symptoms of asthma and other comorbidities - allergic rhinitis, atopic dermatitis, food allergy and chronic urticaria was evaluated after 12 months of treatment with omalizumab. Results: After 12 months of treatment with omalizumab, patients experienced significant improvement in asthma control, reduction of systemic corticosteroids for asthma exacerbations and decreased average daily dose of systemic corticosteroids. The positive effect of treatment with omalizumab was observed in 82.2% of patients with allergic rhinitis, in 85.7% of patients with chronic urticaria, in 82.1% of patients with atopic dermatitis, and in 67.3% of patients with food allergy. Conclusions: Patients with severe asthma treated with omalizumab showed positive effect of anti-IgE therapy not only on the clinical symptoms of asthma, but also on other allergic comorbidities. Most patients with allergic rhinitis, atopic dermatitis, chronic urticaria and food allergy experienced either improvement or complete remission of symptoms of these diseases.

Aim Eighteen years have passed since the last European survey concerning practices in pediatric bronchoscopy was conducted. Therefore, members of the European Respiratory Society (ERS) Pediatric Bronchology Group 7.7, initiated the “European Pediatric Bronchoscopy Survey 2015,” which aimed to assess the current state of this evolving diagnostic and therapeutic procedure in the field of pediatric respiratory medicine. Method A questionnaire was sent to national representatives of 44 European countries with the request to distribute it to all centers performing pediatric bronchoscopies. Questions concerned the following areas of interest: number of procedures, personnel and technical equipment, indications, complications, anesthesia, and diagnostic possibilities. Results In total, 198 European centers from 33 European countries participated in the survey. From 2012 to 2014 a total of 57 145 bronchoscopies were reported. Both flexible and rigid techniques were available at most of the centers. The most frequently mentioned indications were suspected aspiration, infection, radiographic abnormalities, airway obstruction, and cough. Hypoxemia, airway obstruction, and cough were the most common complications mentioned, followed by airway hemorrhage. Most centers were able to perform bronchoalveolar lavage (BAL) and endobronchial biopsies and some performed more special procedures, such as transbronchial biopsies. Interventions like balloon dilation, laser procedures, or stent placement were less common and rarely available. Conclusion Compared to the 1997 survey, our results suggest that pediatric bronchoscopy has become more widely available and established in Europe. Different practices in individual countries suggest that more effort should be put on standardizing bronchoscopic procedures across Europe.

Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.

International audience; The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

Background Bronchial asthma often starts in early childhood. Clinical manifestation of the disease is likely due to inflammatory processes in the airways initiated by various stimuli. Developed remodelling is regularly observed in the bronchial mucosa of adult asthmatics but we still lack information about its onset and latter development with the natural course of the disease. In this study, we analysed histological findings in bronchial biopsies obtained from very young children (under 4 yr of age). We hypothesized that initial undetectable changes in the airway epithelium of children predisposed to asthma may be one of the first mechanisms leading to morphological changes in the bronchial mucosa. Methods We measured the thickness of the basement membrane using a light microscope and analysed the presence of its three basic structural glycoproteins: laminin, tenascin and collagen IV, using immunohistochemical techniques. We compared these findings in children predisposed to asthma according to the selected clinical criteria of the Asthma Predictive Index and in a control group of children. Results We found a significant difference in the thickness of the basement membrane between the two groups. We also found a difference in the subepithelial deposition of laminin and collagen IV in the basement membrane but no difference in the deposition of tenascin. Conclusions We conclude that initial changes leading to further remodelling may start at a very early age even before clinical manifestation of the disease.

Previous reports have described structural airway abnormalities in children with non-cystic fibrosis chronic supportive lung disease as well as obliterative membranes in the major bronchi of cystic fibrosis patients. The putative paradigm proposed in the evolution of these membranes invokes intense inflammation resulting in granulation tissue and neovascularization with the formation of pyogenic granuloma and eventually fibrosis. Our series of four cases widens the spectrum of conditions that may be conducive to large airway obliteration to include non-suppurative chronic infections and possibly immunosuppression. Obliteration of lumina in proximal and distal airways was visualized on bronchoscopy, the latter by the use of the ultrathin bronchoscopes. An attempt at invasive intervention by transbronchial breaching of the obstruction was unsuccessful in three cases, and in one case, the obliterative process resolved spontaneously and without any radiologic trace, presumably by resorption or rupture or through development of collateral ventilation. This series highlights the use of bronchoscopy for diagnosis and occasionally for therapeutic intervention in hitherto little recognized obliterative airway lesions. These acquired obliterative lesions should be considered in the evaluation of patients with isolated non-resolving pulmonary infiltrates or other conditions in which bronchial and bronchiolar patency may be impaired. Pediatr Pulmonol. 2014; 49:E27–E34. © 2013 Wiley Periodicals, Inc.

In the last decades, many researchers have been focusing on early origins of asthma. Despite significant improvement in diagnostics and treatment of asthma even in the youngest age groups, we still lack information about the pathophysiological background in its earliest stages. In our recent work we found difference in the bronchial basement membrane (BM) thickness between young children at risk for developing asthma and age-matched controls with negative asthma predictive index (API) due to higher deposition of laminin, suggesting it being one of the first signs of bronchial remodelling in asthma (Berankova et al: Pediatr Allergy Immunol 2014;25(2):136-42). The same group of children has been followed up in their preschool age (aged 38 to 61 months, median 52 months). In all children we have performed spirometry obtaining relevant results in 6 children from control group (37.5%) and 9 children from risk group (64.3%). The average lung functions (FEV1 and FVC)) were slightly worse in the risk group compared to controls (average FEV1 87.38 vs. 105.67% predicted and average FVC 85.22 vs. 97.67% predicted respectively, but the difference did not reach statistical significance). In both observed groups there was no correlation between FEV1 in preschool age and BM thickness in early age (r 2 =0.083 (p=0.79) in risk group and r 2 =-0.086 (p=0.87) in controls). Similarly there was no correlation between FVC and BM thickness (r 2 =-0.233 (p=0.55) and r 2 =0.143 (p=0.79) in the risk group and controls respectively). Based on the results we conclude, that BM thickening in early age does not predict the lung function impairment in preschool age regardless if children fulfil the API criteria or not.

Introduction 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. Methods The Czech national PCD database has identified 31 pediatric patients, diagnosed based on clinical findings and tests on the ciliated epithelium. Twenty-seven patients from 24 families agreed on genetic testing. In the first step, direct sequencing of selected 13 exons (9 of DNAH5 and 4 of DNAI1) was performed, and then we compared its effectiveness in detecting at least one mutation with results of sequencing all 100 exons of the two genes. Results The sequencing of all exons identified compound heterozygosity for PCD mutations in nine patients from eight families (DNAH5 in eight and DNAI1 in one patient), and heterozygozity for a DNAH5 mutation of uncertain functional significance in one additional patient. The first step of selected exon sequencing detected a mutation in five out of these eight families, its actual sensitivity being 62.5%, with a high predictive value. The phenotypic and clinical characteristics of all the paediatric patients with PCD are shown. Conclusions Selected exon sequencing detects at least one mutated allele in over a half of our patients who have PCD due to DNAH5 or DNAI1 mutations. To lower the costs of the genetic testing, targeted step-wise genetic testing may be a reasonable approach to detect mutations in PCD patients, especially if their phenotype is taken into account. Pediatr Pulmonol. 2012. 47:864–875. © 2012 Wiley Periodicals, Inc.

Dendritic cells (DCs) are specific antigen-presenting cells that play critical roles in the initiation and polarization of immune responses. DCs residing in the lungs might be detected in the bronchoalveolar lavage fluid (BALF). We analysed DC compartment in the peripheral blood and BALF of patients with allergy and in controls. Plasmacytoid and four distinct subsets of myeloid DCs [characterized by the expression of blood dendritic cell antigen (BDCA)-1+ and -3+ and CD16 positivity or negativity] were detected in both tested compartments. We further evaluated the expression of C-type lectins [mannose receptor (MR), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and dendritic and epithelial cells (DEC)-205] relevant to the pathogenesis of asthma. Interestingly, we found a selective increase in the frequency of myeloid DC-expressing BDCA-3 and MR particularly in BALF from allergic patients. Specific and highly statistically significant increase in BDCA-3+ and/or MR+ DCs brings a novel characteristic to BAL analysis in allergic patients.

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies.

Background: Transforming growth factor-s1(TGF-s1) is a pro-fibrotic cytokine. In bronchial asthma (AB) the proliferation of myofibroblasts is considered TGF-s1 dependent and related to chronic epithelial injury. No data is available for other chronic respiratory diseases (CRD) in children. Aim: We sought to evaluate the relationship between epithelial TGF-s1 expression and the number of myofibroblasts in bronchial mucosa of children with various CRD (AB, cystic fibrosis – CF and primary ciliary dyskinesia – PCD). Methods: Thirty-eight children aged 4-19 years were enrolled in the study: 7 with CF, 18 with AB, 7 with PCD and 6 heathy controls. Each patient underwent flexible bronchoscopy with an endobronchial biopsy. Samples were processed using indirect immunohistochemistry. The number of TGF-s1 positive epithelial cells and myofibroblasts was evaluated. Results: The number of TGF-s1 positive epithelial cells was higher in the CRD group compared to controls (54.5, 48-74.5 vs. 21, 15.5-28.5; p Conclusion: These findings suggest that there might be a close relationship between epithelial cells and myofibroblasts in the development of bronchial remodelling. We suggest that bronchial remodelling might be a consequence of non-specific stimuli, a process not specific for AB. Supported by GAUK 360213.

The aim of this article is to describe paediatric highlights from the 2014 European Respiratory Society (ERS) International Congress in Munich, Germany. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) are presented in the context of the current literature., Paediatric highlights from the 2014 ERS International Congress in Munich, Germany http://ow.ly/MaXZv

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).Data and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation.The causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi-allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre-screening step, being followed by an NGS panel for other, much larger, PCD genes.We present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate-size national collection of patients. This strategy has proven to be cost-effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients.

The morbidity and mortality rates in patients with cystic fibrosis (CF) are significantly affected by infections with Burkholderia cepacia complex. In a Czech CF Centre, the prevalence of the infection reached up to 30 %, with the majority of patients found to be infected with Burkholderia cenocepacia (formerly genomovar III of the Burkholderia cepacia complex). Since B. cenocepacia is associated with patient-to-patient transmission and epidemic outbreaks among CF patients, this study sought to examine the epidemiological relatedness between the Czech isolates belonging to the genomovar-homogeneous group. Eighty-three clinical isolates recovered from 67 CF patients were analysed using a random amplified polymorphic DNA (RAPD) assay and macrorestriction typing (SpeI and XbaI) followed by PFGE. A single predominant banding pattern shared by multiple isolates was detected, although SpeI-generated PFGE results yielded a higher rate of inter-pattern variability in comparison to the more uniform RAPD and XbaI-generated PFGE results for this clone. Both typing systems also showed that only three out of 67 patients harboured strains distinct from the major strain type. The dominant clone was characterized by PCR positivity for the B. cepacia epidemic strain marker, PCR negativity for the cable pilin subunit gene and close genetic relatedness to the epidemic strain of RAPD 01 type previously identified in Canada.

Chronic inflammatory changes in the bronchial mucosa have been well documented in patients with established asthma. Much less is known of the changes, which occur in the airways of children early in the evolution of their disease with most of the information based on indirect markers of inflammation only. We evaluated markers of inflammation and tissue re-modelling in bronchial biopsies from children with early respiratory symptoms before a clear clinical diagnosis of bronchial asthma could be made. We examined bronchial biopsies performed in 27 children between the ages of 1.2 and 11.7 yr who were bronchoscoped for a clinical indication because of recurrent or chronic respiratory symptoms. The patients were re-evaluated 22–80 months after the original bronchoscopy to determine whether or not they had subsequently developed bronchial asthma. There were more eosinophils in the bronchial mucosa (129.4 vs. 19.1 cells/mm² of lamina propria, p < 0.001) and the thickness of the subepithelial lamina reticularis was greater (4.65 vs. 3.72 ?m, p = 0.044) in children with bronchial asthma diagnosed at follow-up, compared with the children who did not progress to asthma. Eosinophilic inflammation and airway re-modelling occur early in the natural history of bronchial asthma and are present even before asthma would be diagnosed based on clinical symptoms. Recognition of these changes and their significance for clinical disease should emphasize the need for timely detection and diagnosis of asthma in children to facilitate the early introduction of anti-asthma therapy.

The upper airways play an essential role in the conduction of air into the lungs, and influence the properties of the inhaled air by both the anatomical structure and the functional properties of the mucosa, cartilages and neural and lymphatic tissues. The upper airways also play an important role in the protection of the lower airways, in the formation of the sound and host the sense of olfaction. Main events in the development of the upper airways happen during early embryonic periods. Postnatally, the growth of the airways follows the growth of the skeleton of the head and of the neck and thorax. Growth is accelerated mainly during the first 2 years of life; thereafter, it linearly follows the growth of the body. For a profound understanding of the function of the upper airways, it is important to understand the main developmental events during both prenatal and postnatal periods.

Paediatric fibreoptic bronchoscopy is used for ever wider indications, and increasingly used in many contexts, including paediatric and neonatal intensive care. The report of this Task Force contains an overview on the current applications of paediatric bronchoscopy. The report discusses the facilities and equipment needed for the procedure, including the newly developed bronchoscopes which are allowing intervention even in very small children. The indications of both flexible and rigid bronchoscopes in the context of newer and smaller flexible endoscopic equipment are also considered. The care of the instruments, including disinfection and sterilisation, is fully documented. Patient management is described, including the relative merits of conscious sedation and general anaesthesia, as well as special settings for the procedure, including the needs in intensive care. Special procedures, increasingly performed bronchoscopically are described. These include bronchoalveolar lavage, endobronchial and transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of bronchoscopic procedures, including bronchoscopic research in children. Advances in instrumentation, and also improved anaesthetic techniques, allow fibreoptic bronchoscopy to be safely performed in even very small, sick infants, provided proper precautions are taken.

We developed a nested PCR assay that detects the recA gene of the Burkholderia cepacia complex in sputum. The product of the first PCR round is also used to identify the genomovar of the pathogen. The protocol achieves high sensitivity and specificity with simple interpretation of genomovar status.

This update will describe the paediatric highlights from the 2013 European Respiratory Society (ERS) annual congress in Barcelona, Spain. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) have been chosen by group officers and are presented in the context of current literature.

For the early institution of anti-asthma treatment, reliable markers distinguishing the children with asthma from children with virus-associated wheeze are needed. Serum eosinophilic cationic protein (ECP) has been suggested as a marker correlating with the intensity of eosinophilic inflammation. We have studied 27 children (age 3 to 35 months) admitted with acute bronchial obstruction. Each child had been followed for 12 months after the first episode and then assigned to one of two groups (asthma or non-asthma) based on the clinical course. Serum ECP (s-ECP) was taken at the acute episode and again at least 6 months later, when the child was completely symptom-free. Serum ECP was analyzed using the Pharmacia CAP ECP FEIA immunofluorescence system. Mean s-ECP during the acute episode was 26.5 micrograms/L (5.5-69) in the asthma group (n = 14) and 9.7 (5.2-17 micrograms/L) in the non-asthmatics (n = 13), p < 0.01. There was no difference in the s-ECP analyzed during the symptom-free period. Elevated values of serum ECP taken during, but not outside, the acute episodes of bronchial obstruction may be helpful in predicting the development of bronchial asthma in young children with acute obstructive episodes.

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 eitherDNAH5orDNAI1. In children with PCD, body length/height progressively decreased from+0.40±0.24SDS (the 1st birthday),+0.16±0.23SDS (3 years old), and-0.13±0.21SDS (5 years old) to-0.54±0.19SDS (7 years old;P=0.01versus0),-0.67±0.21SDS (9 years old;P=0.005versus0),-0.52±0.24SDS (11 years old;P=0.04versus0), and-0.53±0.23SDS (13 years old;P=0.03versus0). 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 inDNAH5orDNAI1mutation 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.

Fiberoptic bronchoscopy allows inspection and biopsy of superficial airway structures, typically including epithelium, basement membrane, and lamina propria. Thus, mucosal structures and events can be studied, but the technique is less applicable to studies of smooth muscle. Numerous bronchoscopic studies in adults have established the importance of helper T type 2 (Th2) lymphocyte-mediated, eosinophil-driven airway inflammation in adults with asthma. So commonplace is fiberoptic bronchoscopy in adult volunteers that serial bronchoscopies, for example, endobronchial segmental allergen challenges with repeat bronchoscopy, segmental lavage, and biopsy, are routinely performed. Bronchoscopy has enabled fundamental questions about airway biology and pathophysiological mechanism of inflammation to be addressed, not only in the context of asthma. A MEDLINE search combining [asthma and biopsy and (airway or endobronchial or bronchial or mucosal)] yielded 162 references. However, when this search was combined with [child or paediatric or pediatric or children] this was reduced to only three relevant hits, none of which were in the English language (1–3). One other study looked at changes after respiratory infection (4). Articles about adults have sometimes contained material about older children (5), and there are occasional informative case reports (6). The questions that arise are as follows.

Previous reports have described structural airway abnormalities in children with non-cystic fibrosis chronic supportive lung disease as well as obliterative membranes in the major bronchi of cystic fibrosis patients. The putative paradigm proposed in the evolution of these membranes invokes intense inflammation resulting in granulation tissue and neovascularization with the formation of pyogenic granuloma and eventually fibrosis. Our series of four cases widens the spectrum of conditions that may be conducive to large airway obliteration to include non-suppurative chronic infections and possibly immunosuppression. Obliteration of lumina in proximal and distal airways was visualized on bronchoscopy, the latter by the use of the ultrathin bronchoscopes. An attempt at invasive intervention by transbronchial breaching of the obstruction was unsuccessful in three cases, and in one case, the obliterative process resolved spontaneously and without any radiologic trace, presumably by resorption or rupture or through development of collateral ventilation. This series highlights the use of bronchoscopy for diagnosis and occasionally for therapeutic intervention in hitherto little recognized obliterative airway lesions. These acquired obliterative lesions should be considered in the evaluation of patients with isolated non-resolving pulmonary infiltrates or other conditions in which bronchial and bronchiolar patency may be impaired. Pediatr Pulmonol. 2014; 49:E27–E34. © 2013 Wiley Periodicals, Inc.

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

There are only 4 studies on infant pulmonary function testing (IPFT) performed after repair of CDH. We used a wide spectrum of IPFT methods to test babies in whom CDH repair was performed. We tested 30 infants and toddlers after CDH repair (BW 3.10±0.54 kg [mean±SD]; body length 49.5±2.2 cm). In 4/30 Goretex patch was used (subgroup GORE). Age at testing was 1.32±0.54 (median 1.07) yrs; body weight 9.76±1.25kg (z-score -0,777), body length 78.8±6.7cm (z-score -0,024). The whole-body plethysmography (to measure FRCp and sReff), tidal breathing analysis (tPTEF%tE), baby resistance/compliance (specific Crs) and RTC method (V´maxFRC) were performed. Standard protocols1,2 and proper reference values3,4 were used. FRCp equals 126.5±36.9% pred (P Our cohort had normal body length but mildly lowered body weight. Neither central airway (aw) obstruction nor restrictive pattern was found. Mild peripheral aw obstruction, mild (secondary) hyperinflation and mildly decreased specific Crs was found. References: 1.Hammer J, Eber E (eds). Pediatric Pulmonary Function Testing, 2005, Basel, Karger; 2.Gappa M et al. ERS/ATS Task Force. Eur Respir J. 2001 Jan;17(1):141-8; 3.Hulskamp G et al. Am J Respir Crit Care Med 2003;168:1003-9; 4.Koumbourlis AC et al. Pediatr Pulmonol. 2004 Apr;37(4):318-23. Supported by the grant NS 10572-3/2009 and grant GAUK 62809.

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.The Czech national PCD database has identified 31 pediatric patients, diagnosed based on clinical findings and tests on the ciliated epithelium. Twenty-seven patients from 24 families agreed on genetic testing. In the first step, direct sequencing of selected 13 exons (9 of DNAH5 and 4 of DNAI1) was performed, and then we compared its effectiveness in detecting at least one mutation with results of sequencing all 100 exons of the two genes.The sequencing of all exons identified compound heterozygosity for PCD mutations in nine patients from eight families (DNAH5 in eight and DNAI1 in one patient), and heterozygozity for a DNAH5 mutation of uncertain functional significance in one additional patient. The first step of selected exon sequencing detected a mutation in five out of these eight families, its actual sensitivity being 62.5%, with a high predictive value. The phenotypic and clinical characteristics of all the paediatric patients with PCD are shown.Selected exon sequencing detects at least one mutated allele in over a half of our patients who have PCD due to DNAH5 or DNAI1 mutations. To lower the costs of the genetic testing, targeted step-wise genetic testing may be a reasonable approach to detect mutations in PCD patients, especially if their phenotype is taken into account.

Bronchoscopy provides a unique technical possibility to visualize the airways, document pathological lesions and collect relevant biological material directly from the lower airways. Diagnostic flexib

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease. Copyright

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and sarcoidosis belong to interstitial lung diseases (ILD) where an imbalance of regulatory, profibrotic and antifibrotic cytokines is hypothesized. The relationship of bronchoalveolar lavage (BAL) fluid (BALF) cytokines, BALF cell profile and ILD course is supposed. The aim of our study was to correlate BALF cytokine and chemokine levels with BALF cellular characteristics and lung function parameters in different ILD. Twenty-two sarcoidosis, seven IPF and 11 HP patients underwent lung function tests and BAL. The BALF differential cell counts and superficial cell markers were characterized, and MCP-1, MIP-1alpha, MIP-1beta, RANTES, epithelial neutrophil-activating protein (ENA)-78, FGF, G-CSF, GM-CSF, IFN-gamma, interleukin (IL)-1alpha, IL-1RA, IL-1beta, -2beta, -4beta, -5beta, -6beta, -8beta, -10beta, -17beta, tumour necrosis factor (TNF)-alpha, thromobopoietin (Tpo) and vascular endothelial growth factor (VEGF) values measured. The BALF VEGF values were highest in sarcoidosis (P = 0.0526). IL-1RA values were higher in IPF and HP compared with sarcoidosis (P = 0.0334). IL-8/ENA-78 ratio positively correlated with BALF neutrophil counts in IPF (r = 0.89, P = 0.04). Vital capacity and TL(CO) values positively correlated with VEGF and negatively with IL-8 BALF levels in all ILDs but the correlations were most significant in sarcoidosis group. We suppose that VEGF plays a role in ILDs' early phases and has rather angiogenic than profibrotic effect. On the contrary, IL-8 is probably upregulated in advanced ILDs with prominent fibrosis and marked lung functions decline. We state that BALF VEGF, IL-8 and ENA-78 levels and IL-8/ENA-78 ratio could become useful markers of ILDs' phase, activity and prognosis. They might also be helpful in treatment modality choice.

The aim of our study is to investigate correlations of T(H)1/T(H)2 cytokine gene polymorphisms and bronchoalveolar lavage fluid (BALF) cytokine values in interstitial lung diseases (ILD).In 16 sarcoidosis, 7 idiopathic pulmonary fibrosis (IPF) and 8 hypersensitivity pneumonitis (HP) patients we evaluated IL-1 alpha, -1R, -1RA, -2, -4, -4R alpha, -6, -10, -12, IFN-gamma, TGF-beta1 and TNF-alpha gene polymorphisms in peripheral blood, and MCP-1,MIP-1 alpha, MIP-1 beta, RANTES, ENA-78, FGF, G-CSF, GM-CSF, IFN-gamma, IL-1 alpha, IL-1RA, IL-1 beta, -2, -4, -5, -6, -8, -10, -17, TNF-alpha, Tpo and VEGF values in BALF.We found higher TNF-alpha values in IL-1R pst 1970 TT homozygotes regardless of diagnosis (p=0.0126). In the sarcoidosis group IL-4R alpha(+1902)AA and IL-10(-1082)G allele correlated with higher BALF ENA-78 levels (p=0.0258, p=0.0230). In the HP group the IL-6(-174)CG and IL-6(nt565)AG correlated with higher ENA-78 BALF levels (p=0.0253). In the IPF group the IL-1 beta +3962 CC homozygotes had lower IL-1RA BALF values (p=0.046). BALF chemokine values did not differ between ILD subgroups, except for IL-8, which was higher in stage III sarcoidosis patients compared to stage I.Our results show a probable influence of gene polymorphisms, namely IL-4R alpha and IL-10 on ENA-78 BALF levels in sarcoidosis, IL-6 on ENA-78 BALF levels in HP and IL-1-beta on IL-1RA BALF values in the IPF group. The TNF-alpha BALF values correlated with IL-1R pst 1970 gene polymorphisms.

Atopic preschool children are more likely to develop persistent wheezing, which could be a consequence of early airway remodeling. Protease–antiprotease balance between MMP-9 and its cognate inhibitor TIMP-1 may be involved in this process. Our hypothesis was that atopic wheezing preschool children would have an imbalance of MMP-9 to TIMP-1 in bronchoalveolar lavage (BAL). BAL from 52 preschool wheezers was compared with 14 controls without wheeze. A subgroup completed an International Study of Asthma and Allergy in Childhood symptom questionnaire 2 y later. Molar ratios of MMP-9/TIMP-1 were higher in wheezy children (p < 0.001; median 4.0%, range 0–8.7) than controls (0.6%, 0–1.8), and showed an excess of TIMP-1 in the airway. BAL TIMP-1 was raised in children with persistent wheezing (p = 0.028; 34.4 ng/mL, 9.1–93.1 compared with 10.6 ng/mL 6.1–18.6), as was serum levels of intercellular adhesion molecule-1 (p = 0.027). The absolute concentration of TIMP-1 in the airway, rather than its molar ratio with MMP-9, was associated with persistent wheezing. The processes involved with airway remodeling are complex but excess TIMP-1 may impede matrix protein turnover and thereby contribute to persistent changes in airway structure and wheezing.

Indacaterol is a novel, inhaled, once-daily beta2-agonist.To investigate the safety and tolerability of indacaterol at doses of 400 and 800 microg/d.Randomized, double-blind, placebo-controlled, parallel-group, multicenter, 28-day study. Patients with persistent asthma (forced expiratory volume in 1 second [FEV1]or =-60% predicted,or =1,600 microg of beclomethasone dipropionate or equivalent daily) received indacaterol, 400 microg (n = 59) or 800 microg (n = 59), or placebo (n = 26) once daily via a single-dose dry powder inhaler. Safety assessments were performed before and after dosing on days 1, 14, and 28, with particular attention to key beta2-agonist safety variables.A total of 144 patients were randomized, with 135 (93.8%) completing the study. Indacaterol was well tolerated: the incidence of adverse events (AEs) was similar between the active and placebo groups, and AEs, when they occurred, were mild or moderate for most (98.2%). There was no dose-response relationship between indacaterol and the incidence of AEs (400 microg, 40.7%; 800 microg, 37.3%; and placebo, 38.5%). Few AEs considered as beta2-agonist class effects occurred (none leading to withdrawal). Small differences between indacaterol and placebo in mean serum potassium (or =-0.29 mmol/L) and glucose (or =0.93 mmol/L) levels were occasionally statistically significant (P.05) but not regarded as clinically meaningful. As expected for a beta2-agonist, there was some indication of a trend in QTc prolongation with increasing exposure (maximum mean change, 8.9 milliseconds; P.05 vs placebo). Significant increases in FEV1 (P.05) were seen at all postbaseline time points for both indacaterol doses vs placebo, with indacaterol-placebo differences 30 minutes after dosing of 0.21 to 0.25 L and before dosing on days 14 and 28 (approximately 24 hours after the previous dose) of 0.15 to 0.23 L.Indacaterol had a good overall safety profile and was well tolerated at both doses, with predose FEV1 results on days 14 and 28 indicating 24-hour bronchodilator efficacy.

Contains fulltext : 69668.pdf (Publisher’s version ) (Closed access) There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.