Bronchoscopy findings in children with congenital lung and lower airway abnormalities.

Congenital lung and lower airway abnormalities are rare, but they are an important differential diagnosis in children with respiratory diseases, especially if the disease is recurrent or does not resolve. The factors determining the time of presentation of congenital airway pathologies include the severity of narrowing, association with other lesions and the presence or absence of congenital heart disease (CHD). Bronchoscopy is required in these cases to assess the airway early after birth or when intubation and ventilation are difficult or not possible. Many of these conditions have associated abnormalities that must be diagnosed early, as this determines surgical interventions. It may be necessary to combine imaging and bronchoscopy findings in these children to determine the correct diagnosis as well as in operative management. Endoscopic interventional procedures may be needed in many of these conditions, ranging from intubation to balloon dilatations and aortopexy. This review will describe the bronchoscopic findings in children with congenital lung and lower airway abnormalities, illustrate how bronchoscopy can be used for diagnosis and highlight the role of interventional bronchoscopy in the management of these conditions.

Cryoprobe for Endoscopic Enucleation in Children with Pulmonary Tuberculosis: Effective but Not Without Danger - Case Report and Review of Literature.

INTRODUCTION: Tuberculosis (TB) in children under 15 years often results in airway compression, with bronchus intermedius (BI) being the most common site. Endoscopic enucleations can be used to remove lymph nodes and establish an airway in severe cases. Both rigid and flexible bronchoscopy are suitable, with alligator forceps being preferred for its ability to extract tissue. Recent studies have also explored cryoprobe enucleation. CASE PRESENTATION: An HIV-positive boy with persistent symptoms after 9 months of TB treatment was diagnosed based on his mother's and sister's Xpert MTB/RIF positive status. He was started on 4-drug TB treatment, but the child remained clinically symptomatic with abnormal chest X-ray and unconfirmed TB. Bronchoscopy was performed, revealing complete obstruction of BI due to caseating granulomas causing collapse of the right middle and lower lobes. Cryotherapy was used to recanalize the airway, and follow-up bronchoscopy confirmed patent BI. CONCLUSION: While cryotherapy was effective in the restoration of airway patency in this case, there is a lack of knowledge about its use in children.

[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

Complicated intrathoracic tuberculosis: Role of therapeutic interventional bronchoscopy.

In recent years bronchoscopy equipment has been improved with smaller instruments and larger size working channels. This has ensured that bronchoscopy offers both therapeutic and interventional options. As the experience of paediatric interventional pulmonologists continues to grow, more interventions are being performed. There is a scarcity of published evidence in the field of interventional bronchoscopy in paediatrics. This is even more relevant for complicated pulmonary tuberculosis (PTB). Therapeutic interventional bronchoscopy procedures can be used in the management of complicated tuberculosis, including for endoscopic enucleations, closure of fistulas, dilatations of bronchial stenosis and severe haemoptysis. Endoscopic therapeutic procedures in children with complicated TB may prevent thoracotomy. If done carefully these interventional procedures have a low complication rate.

Intrathoracic tuberculosis: Role of interventional bronchoscopy in diagnosis.

Tuberculosis (TB) is the leading cause of death from a single infectious agent globally. Mortality is related to the delay in diagnosis and starting treatment. According to new guidelines it is very important to classify pulmonary tuberculosis (PTB) as severe or not severe disease due to the difference in treatment duration. Bronchoscopy is the gold standard for assessing the degree of airway compression and obstruction in paediatric PTB. Paediatric bronchoscopy has evolved from a primarily diagnostic procedure to include interventional bronchoscopy for diagnostic purposes. Endobronchial ultrasound (EBUS) has increased the potential of sampling mediastinal lymph nodes both for histological diagnosis and microbiological confirmation.

Patient rotation chest X-rays and the consequences of misinterpretation in paediatric radiology.

PURPOSE: We aimed to demonstrate the consequences of rotation on neonatal chest radiographs and how it affects diagnosis. In addition, we demonstrate methods for determining the presence and direction of rotation. BACKGROUND: Patient rotation is common in chest X-rays of neonates. Rotation is present in over half of chest X-rays from the ICU, contributed to by unwillingness of technologists to reposition new-borns for fear of dislodging lines and tubes. There are six main effects of rotation on supine paediatric chest X-rays: 1) unilateral hyperlucency of the side that the patient is rotated towards; 2) the side 'up' appears larger; 3) apparent deviation of the cardiomediastinal shadow in the direction that the chest is rotated towards; 4) apparent cardiomegaly; 5) distorted cardio-mediastinal configuration; and 6) reversed position of the tips of the umbilical artery and vein catheters with rotation to the left. These effects can cause diagnostic errors due to misinterpretation, including air-trapping, atelectasis, cardiomegaly, and pleural effusions, or disease may be masked. We demonstrate the methods of evaluating rotation with examples, including a 3D model of the bony thorax as a guide. In addition, multiple examples of the effects of rotation are provided including examples where disease was misinterpreted, underestimated or masked. CONCLUSION: Rotation is often unavoidable in neonatal chest X-rays, especially in the ICU. It is therefore important for physicians to recognise rotation and its effects, and to be aware that it can mimic or mask disease.

Effects of a Partially Supervised Conditioning Program in Cystic Fibrosis: An International Multicenter, Randomized Controlled Trial (ACTIVATE-CF).

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel-arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged at least 12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, whereas the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted FEV1 (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: A total of 117 patients (40% of target sample size) were randomized to an intervention (n = 60) or control group (n = 57). After 6 months, ΔFEV1 was significantly higher in the control group compared with the intervention group (2.70% predicted [95% confidence interval, 0.13-5.26]; P = 0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group.

Changing paradigms in the treatment of gastrointestinal complications of cystic fibrosis in the era of cystic fibrosis transmembrane conductance regulator modulators.

Cystic fibrosis (CF) - although primarily a lung disease - also causes a variety of gastrointestinal manifestations which are important for diagnosis, prognosis and quality of life. All parts of the gastrointestinal tract can be affected by CF. Besides the well-known pancreatic insufficiency, gastroesophageal reflux disease, liver disease and diseases of the large intestine are important pathologies that impact on prognosis and also impair quality of life. Diagnosis and management of gastrointestinal manifestations will be discussed in this review. Since optimisation of CF therapy is associated with a significantly longer life-span of CF patients nowadays, also gastrointestinal malignancies, which are more common in CF than in the non-CF population need to be considered. Furthermore, novel evidence on the role of the gut microbiome in CF is emerging. The introduction of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators gives hope for symptom alleviation and even cure of gastrointestinal manifestations of CF.

Paediatric pulmonary actinomycosis: A forgotten disease.

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Actinomycosis develops when there is disruption of the mucosal barrier, and invasion and systemic spread of the organism, which can lead to endogenous infection affecting numerous organs. It is known to spread in tissue through fascial planes and most often involves the cervicofacial (55%), abdominopelvic (20%) and thoracic (15%) soft tissue. Pulmonary actinomycosis is rare in patients under the age of five years, with the median reported age in the fifth decade. Clinical findings include chest wall mass (49%), cough (40%), pain (back, chest, shoulders) (36%), weight loss (19%), fever (19%), Draining sinuses (15%) and hemoptysis (9%). Chest x-ray findings in pulmonary actinomycosis are mostly nonspecific and can overlap with pulmonary tuberculosis, foreign body aspiration and malignancy. Endobronchial tissue aggregates may show sulphur granules, with yellow to white conglomerate areas of gram positive Actinomyces. Removal or biopsy of these large endobronchial masses must be done with care, because of the risk of bleeding and large airway obstruction. The cytology on bronchoalveolar lavage fluid may show Periodic acid-Schiff (PAS) positive stain, ZN negative and Gram-positive filamentous bacilli which is morphologically suggestive of Actinomycosis. Actinomyces spp is highly susceptible to beta lactam antibiotics, penicillin G, and amoxicillin. A minimum of 3-6 months is needed but up to 20 months of treatment may be needed. Early diagnosis and correct treatment can lead to a good prognosis with a low mortality.

Paediatric pulmonary echinococcosis: A neglected disease.

Echinococcosis is a worldwide public health problem causing considerable paediatric morbidity and mortality in endemic areas. The presentation of cystic echinococcosis (CE) varies by age. Unlike adults, where hepatic involvement is common, pulmonary CE is the dominant site in the paediatric population. Pulmonary cysts are typically first seen on chest X-ray, either as an incidental finding or following respiratory symptoms after cyst rupture or secondary infection of the cyst. In children, pulmonary cysts have a broad differential diagnosis, and a definitive diagnosis relies on the combination of imaging, serology, and histology. In countries with high infectious burdens from diseases such as acquired immunodeficiency syndrome (AIDS) and tuberculosis (TB), the diagnosis is additionally challenging, as atypical infections are more common than in developed countries. Pulmonary CE is treated with a combination of surgery and chemotherapy.

Bronchoscopy precautions and recommendations in the COVID-19 pandemic.

As the airways of SARS-CoV-2 infected patients contain a high viral load, bronchoscopy is associated with increased risk of patient to health care worker transmission due to aerosolised viral particles and contamination of surfaces during bronchoscopy. Bronchoscopy is not appropriate for diagnosing SARS-CoV-2 infection and, as an aerosol generating procedure involving a significant risk of transmission, has a very limited role in the management of SARS-CoV-2 infected patients including children. During the SARS-CoV-2 pandemic rigid bronchoscopy should be avoided due to the increased risk of droplet spread. Flexible bronchoscopy should be performed first in SARS-CoV-2 positive individuals or in unknown cases, to determine if rigid bronchoscopy is indicated. When available single-use flexible bronchoscopes may be considered for use; devices are available with a range of diameters, and improved image quality and degrees of angulation. When rigid bronchoscopy is necessary, jet ventilation must be avoided and conventional ventilation be used to reduce the risk of aerosolisation. Adequate personal protection equipment is key, as is training of health care workers in correct donning and doffing. Modified full face masks are a practical and safe alternative to filtering facepieces for use in bronchoscopy. When anaesthetic and infection prevention control protocols are strictly adhered to, bronchoscopy can be performed in SARS-CoV-2 positive children.

Pediatric Airway Endoscopy: Recommendations of the Society for Pediatric Pneumology.

For many decades, pediatric bronchoscopy has been an integral part of the diagnosis and treatment of acute and chronic pulmonary diseases in children. Rapid technical advances have continuously influenced the performance of the procedure. Over the years, the application of pediatric bronchoscopy has considerably expanded to a broad range of indications. In this comprehensive and up-to-date guideline, the Special Interest Group of the Society for Pediatric Pneumology reviewed the most recent literature on pediatric bronchoscopy and reached a consensus on a safe technical performance of the procedure.

Volatile Organic Compounds, Bacterial Airway Microbiome, Spirometry and Exercise Performance of Patients after Surgical Repair of Congenital Diaphragmatic Hernia.

The aim of this study was to analyze the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance in congenital diaphragmatic hernia (CDH) patients compared to healthy age and sex-matched controls. A total of nine patients (median age 9 years, range 6-13 years) treated for CDH were included. Exhaled VOCs were measured by GC-MS. Airway microbiome was determined from deep induced sputum by 16S rRNA gene sequencing. Patients underwent conventional spirometry and exhausting bicycle spiroergometry. The exhaled VOC profile showed significantly higher levels of cyclohexane and significantly lower levels of acetone and 2-methylbutane in CDH patients. Microbiome analysis revealed no significant differences for alpha-diversity, beta-diversity and LefSe analysis. CDH patients had significantly lower relative abundances of Pasteurellales and Pasteurellaceae. CDH patients exhibited a significantly reduced Tiffeneau Index. Spiroergometry showed no significant differences. This is the first study to report the VOCs profile and airway microbiome in patients with CDH. Elevations of cyclohexane observed in the CDH group have also been reported in cases of lung cancer and pneumonia. CDH patients had no signs of impaired physical performance capacity, fueling controversial reports in the literature.

ERS statement on tracheomalacia and bronchomalacia in children.

Tracheomalacia and tracheobronchomalacia may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low-contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions, but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics (as well as treatment of comorbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, continuous positive airway pressure is the most commonly used modality either via a face mask or tracheostomy. Parents of children with tracheobronchomalacia report diagnostic delays and anxieties about how to manage their child's condition, and want more information. There is a need for more research to establish an evidence base for malacia. This European Respiratory Society statement provides a review of the current literature to inform future study.

Lung disease caused by ABCA3 mutations.

BACKGROUND: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort. METHODS: We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015. RESULTS: Of 22 homozygous (15 male) and 18 compound heterozygous patients (3 male), 37 presented with neonatal respiratory distress syndrome as term babies. At follow-up, two major phenotypes are documented: patients with (1) early lethal mutations subdivided into (1a) dying within the first 6 months or (1b) before the age of 5 years, and (2) patients with prolonged survival into childhood, adolescence or adulthood. Patients with null/null mutations predicting complete ABCA3 deficiency died within the 1st weeks to months of life, while those with null/other or other/other mutations had a more variable presentation and outcome. Treatment with exogenous surfactant, systemic steroids, hydroxychloroquine and whole lung lavages had apparent but many times transient effects in individual subjects. CONCLUSIONS: Overall long-term (>5 years) survival of subjects with two disease-causing ABCA3 mutations was <20%. Response to therapies needs to be ascertained in randomised controlled trials.

ERS statement: interventional bronchoscopy in children.

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.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.

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.

Assessment and causes of stridor.

Stridor is a variably pitched respiratory sound, caused by abnormal air passage during breathing and often is the most prominent sign of upper airway obstruction. It is usually heard on inspiration (typically resulting from supraglottic or glottic obstruction) but also can occur on expiration (originating from obstruction at or below glottic level and/or severe upper airway obstruction). Stridor due to congenital anomalies may exist from birth or may develop within days, weeks or months. Various congenital and acquired disorders prevail in neonates, infants, children, and adolescents, and have to be distinguished. History, age of the child and physical examination together often allow a presumptive diagnosis. Further investigations may be necessary to establish a definite diagnosis, and flexible airway endoscopy is the diagnostic procedure of choice in most circumstances ("stridor is visible").