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.

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.

Interventional bronchoscopy in pediatric pulmonary tuberculosis.

INTRODUCTION: Lymphobronchial tuberculosis (TB) is common in children with primary TB and enlarged lymph nodes can cause airway compression of the large airways. If not treated correctly, airway compression can result in persistent and permanent parenchymal pathology, as well as irreversible lung destruction. Bronchoscopy was originally used to collect diagnostic samples; however, its role has evolved, and it is now used as an interventional tool in the diagnosis and management of complicated airway disease. Endoscopic treatment guidelines for children with TB are scarce. AREAS COVERED: The role of interventional bronchoscopy in the diagnosis and management of complicated pulmonary TB will be discussed. This review will provide practical insights into how and when to perform interventional procedures in children with complicated TB for both diagnostic and therapeutic purposes. This discussion incorporates current scientific evidence and refers to adult literature, as some of the interventions have only been done in adults but may have a role in children. Limitations and future perspectives will be examined. EXPERT OPINION: Pediatric pulmonary TB lends itself to endoscopic interventions as it is a disease with a good outcome if treated correctly. However, interventions must be limited to safeguard the parenchyma and prevent permanent damage.

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.

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.

Cystic fibrosis related diabetes is not associated with maximal aerobic exercise capacity in cystic fibrosis: a cross-sectional analysis of an international multicenter trial.

BACKGROUND: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO2peak), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO2peak. We investigated associations between CFRD and VO2peak following rigorous control for confounders including objectively measured physical activity. METHODS: Baseline data from the international multicenter trial ACTIVATE-CF with participants ≥12 years performing up to 4 h per week of vigorous physical activity were used for this project. Multivariable models were computed to study associations between CFRD and VO2peak (mL.min-1) adjusting for a set of pre-defined covariates: age, sex, weight, forced expiratory volume in 1 s (FEV1), breathing reserve index, Pseudomonas aeruginosa infection, and physical activity (aerobic step counts from pedometry). Variables were selected based on their potential confounding effect on the association between VO2peak and CFRD. RESULTS: Among 117 randomized individuals, 103 (52% female) had a maximal exercise test and were included in the analysis. Participants with (n = 19) and without (n = 84) CFRD did not differ in FEV1, physical activity, nutritional status, and other clinical characteristics. There were also no differences in VO2peak (mL.min-1 or mL.kg-1.min-1 or% predicted). In the final multivariable model, all pre-defined covariates were significant predictors of VO2peak (mL.min-1), however CFRD [coefficient 82.1, 95% CI -69.5 to 233.8, p = 0.28] was not. CONCLUSIONS: This study suggests no meaningful differences in VO2peak between people with and without CFRD given comparable levels of physical activity.

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.

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.

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.

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.

[Osteoporosis in pneumological diseases : Joint guideline of the Austrian Society for Bone and Mineral Research (ÖGKM) and the Austrian Society for Pneumology (ÖGP)]. / Osteoporose bei pneumologischen Erkrankungen : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen und Mineralstoffwechsel (ÖGKM) und der Österreichischen Gesellschaft für Pneumologie (ÖGP).

Chronic inflammation induces proinflammatory cytokine cascades. In addition to systemic inflammation, hypoxemia, hypercapnia, a catabolic metabolism, gonadal or thyroid dysfunction, musculoskeletal dysfunction and inactivity as well as vitamin D deficiency contribute to an increased risk of fragility fractures. Iatrogenic causes of osteoporosis are long-term use of inhaled or systemic glucocorticoids (GC). Inhalative GC application in asthma is often indicated in childhood and adolescence, but interstitial lung diseases such as chronic organizing pneumonia, COPD, sarcoid or rheumatic diseases with lung involvement are also treated with inhalative or oral GC. In patients with cystic fibrosis, malabsorption in the context of pancreatic insufficiency, hypogonadism and chronic inflammation with increased bone resorption lead to a decrease in bone structure. After lung transplantation, immunosuppression with GC is a risk factor.The underlying pneumological diseases lead to a change in the trabecular and cortical bone microarchitecture and to a reduction in osteological formation and resorption markers. Hypercapnia, acidosis and vitamin D deficiency can accelerate this process and thus increase the individual risk of osteoporotic fragility fractures.A bone mineral density measurement with a T­Score < -2.5 is a threshold value for the diagnosis of osteoporosis; in contrast the vast majority of all osteoporotic fractures occur with a T­Score > -2.5. A history of low-trauma fracture indicates osteological therapy.All antiresorptive or anabolic drugs approved in Austria for the treatment of osteoporosis are also indicated for pneumological patients with an increased fragility fracture risk of bone fractures in accordance with the national reimbursement criteria.

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.

Cystic Fibrosis Newborn Screening in Austria Using PAP and the Numeric Product of PAP and IRT Concentrations as Second-Tier Parameters.

In Austria, newborns have been screened for cystic fibrosis (CF) by analyzing immunoreactive trypsinogen (IRT) from dried blood spots (DBS)s for nearly 20 years. Recently, pancreatitis-associated protein (PAP) analysis was introduced as a second-tier test with the aim of reducing recalls for second DBS cards while keeping sensitivity high. For 28 months, when IRT was elevated (65-130 ng/mL), PAP was measured from the first DBS (n = 198,927) with a two-step cut-off applied. For the last 12 months of the observation period (n = 85,421), an additional IRT×PAP cut-off was introduced. If PAP or IRT×PAP were above cut-off, a second card was analyzed for IRT and in case of elevated values identified as screen-positive. Above 130 ng/mL IRT in the first DBS, newborns were classified as screen-positive. IRT analysis of first DBS resulted in 1961 (1%) tests for PAP. In the first 16 months, 26 of 93 screen-positive were confirmed to have CF. Two false-negatives have been reported (sensitivity = 92.8%). Importantly, less than 30% of families compared to the previous IRT-IRT screening scheme had to be contacted causing distress. Adding IRT×PAP caused a marginally increased number of second cards and sweat tests to be requested during this period (15 and 3, respectively) compared to the initial IRT-PAP scheme. One case of confirmed CF was found due to IRT×PAP, demonstrating an increase in sensitivity. Thus, the relatively simple and economical algorithm presented here performs effectively and may be a useful model for inclusion of CF into NBS panels or modification of existing schemes.

The use of pediatric flexible bronchoscopy in the COVID-19 pandemic era.

On March 11, 2020, the World Health Organization (WHO) declared the pandemic because of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In January 2020, the first transmission to healthcare workers (HCWs) was described. SARS-CoV-2 is transmitted between people because of contact, droplets, and airborne. Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures like flexible bronchoscopy. To date, although the role of children in the transmission of SARS-CoV-2 is not clear the execution of bronchoscopy is associated with a considerably increased risk of SARS-CoV-2 transmission to HCWs. The aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy. We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases. We reviewed major recommendations and position statements published at the moment by the American Association for Bronchology and Interventional Pulmonology, WHO, European Center for Disease Prevention and Control and expert groups on the management of patients with COVID-19 to limit transmission among HCWs. To date there is a lack of recommendations for safe bronchoscopy during the pandemic period. The main indications concern adults and little has been said about children. We have summarized available recommendations and we have applied them to pediatric bronchoscopy.

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.

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.

Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial.

BACKGROUND: Lancovutide activates a chloride channel (TMEM-16A) other than the cystic fibrosis (CF) transmembrane conductance regulator protein and could benefit CF patients. METHODS: In this randomized, multi-center, double-blind, placebo-controlled, parallel-group trial 161 patients ≥12 years with a confirmed diagnosis of CF were randomized to either placebo (saline) or active drug in 3 different dosing schemes of 2.5mg inhaled lancovutide (once daily, every other day or twice a week) for eight weeks. The primary endpoint was the change in the forced expiratory volume in 1 second (FEV1) percent predicted. Secondary endpoints included further lung function parameters (FEV1 (absolute), functional vital capacity percent predicted, forced expiratory flow percent predicted, pulse oximetry), quality of life assessment, pulmonary exacerbations, hospitalization due to pulmonary exacerbations, time to first pulmonary exacerbation, duration of anti-inflammatory, mucolytic or antibiotic treatment, and safety. RESULTS: There was no significant difference in the change in FEV1 percent predicted, quality of life, other lung function parameters, pulmonary exacerbations or requirement of additional treatment between groups. Overall, the inhalation of lancovutide was safe although a higher rate of adverse events, especially related to the respiratory system, occurred as compared to placebo. CONCLUSIONS: Lancovutide did not improve FEV1 percent predicted when compared to placebo (NCT00671736).

[Masterplan 2025 of the Austrian Society of Pneumology (ASP)-the expected burden and management of respiratory diseases in Austria]. / Masterplan 2025 der Österreichischen Gesellschaft für Pneumologie (ÖGP) ­ die erwartete Entwicklung und Versorgung respiratorischer Erkrankungen in Österreich.

Scientific Members of the Austrian Society of Pneumology describe the expected development in respiratory health and provide guidance towards patient-oriented and cost-efficient respiratory care in Austria.Methods: In November 2017, respiratory care providers (physicians, nurses, physiotherapists) together with patient's advocacy groups and experts in health development, collaborated in workshops on: respiratory health and the environment, bronchial asthma and allergy, COPD, pediatric respiratory disease, respiratory infections, sleep disorders, interventional pneumology, thoracic oncology and orphan diseases.Results: Respiratory disease is extremely prevalent and driven by ill-health behavior, i.e. cigarette smoking, over-eating and physical inactivity. For the majority of respiratory diseases increased prevalence, but decreased hospitalizations are expected.The following measures should be implemented to deal with future challenges:1. Screening and case-finding should be implemented for lung cancer and COPD.2. E-health solutions (telemedicine, personal apps) should be used to facilitate patient management.3. Regional differences in respiratory care should be reduced through E­health and harmonization of health insurance benefits across Austria.4. Patient education and awareness, to reduce respiratory health illiteracy should be increased, which is essential for sleep disorders but relevant also for other respiratory diseases.5. Respiratory care should be inter-professional, provided via disease-specific boards beyond lung cancer (for ILDs, sleep, allergy)6. Programs for outpatient's pulmonary rehabilitation can have a major impact on respiratory health.7. Increased understanding of molecular pathways will drive personalized medicine, targeted therapy (for asthma, lung cancer) and subsequently health care costs.