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.

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").

Severe primary pulmonary lymphangiectasis in a premature infant: management and follow up to early childhood.

Primary pulmonary lymphangiectasis (PPL) is a rare congenital developmental abnormality of the lung with a generally poor prognosis. Only a limited number of patients with neonatal-onset PPL have been reported to survive. We present the case of a male preterm infant (gestational age 34 weeks 6 days) with histologically confirmed PPL, complicated by hydrops fetalis, bilateral hydrothorax (treated in utero with pleuro-amniotic shunts), and immediate respiratory distress at birth. He survived after extensive neonatal intensive care therapy and was discharged home at the age of 7 months. At last follow up he was 3 years 7 months old, still requiring assisted ventilation via tracheostomy, having recurrent episodes of wheezing and had mild global developmental delay. This case demonstrates that survival beyond the neonatal period is possible even with severe PPL but long-term morbidity may be relevant, and multidisciplinary management and close follow up are essential.

Management of acute severe upper airway obstruction in children.

There are many causes of acute severe upper airway obstruction (UAO) in children. The timing of symptom onset and the presence of fever will help to distinguish infectious from non-infectious conditions. Signs and symptoms from congenital malformations often present at birth but may also develop over time. The most common cause of UAO in children is croup. Choking on a foreign body also occurs relatively frequently. Evaluation of the child with UAO starts with a detailed history followed by a thorough physical examination, including an assessment of severity. Severe airway obstruction will result in respiratory failure. This situation requires an immediate response. A child with partial airway obstruction may initially have an adequate airway. However, this situation can deteriorate rapidly. Therefore, providing supportive care and mobilizing resources for definitive airway management may be the most appropriate interventions.

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Management of patients with SARS-CoV-2 infections with focus on patients with chronic lung diseases (as of 10 January 2022) : Updated statement of the Austrian Society of Pneumology (ASP).

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV­2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV­2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV­2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. METHODS: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. RESULTS: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). CONCLUSION: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020.

BACKGROUND: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). METHODS: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. RESULTS: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). CONCLUSIONS: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.

Guidelines for diagnosis and management of congenital central hypoventilation syndrome.

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of ventilation and a global autonomic dysfunction. Paired-like homeobox 2B (PHOX2B) mutations are found in most of the patients with CCHS. In recent years, the condition has evolved from a life-threatening neonatal onset disorder to include broader and milder clinical presentations, affecting children, adults and families. Genes other than PHOX2B have been found responsible for CCHS in rare cases and there are as yet other unknown genes that may account for the disease. At present, management relies on lifelong ventilatory support and close follow up of dysautonomic progression. BODY: This paper provides a state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research. CONCLUSION: Awareness and knowledge of the diagnosis and management of this rare disease should be brought to a large health community including adult physicians and health carers.