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.

Gorham-Stout syndrome is a rare disease characterized by vascular proliferation in the bones, effecting osteolysis. When it is complicated by chylothorax, the prognosis is poor. The present case illustrates successful management of chylothorax by a combination of surgery (thoracic duct ligation and excision of lymphangiomatous tissue combined with pleurodesis) and treatment with alpha-2b interferon. Treatment in 38 published cases is reviewed.

Fourteen patients with cystic fibrosis were trained in 2 self-administered chest physiotherapy (PT) techniques: high-pressure PEP-mask physiotherapy (PEP), and autogenic drainage (AD). They then visited the clinic on 5 consecutive days, and, in a random order, performed 1 of the following: PEP, AD, PEP followed by AD (PEP-AD), AD followed by PEP (AD-PEP), and, no PT except for spontaneous coughing. Lung function was measured repeatedly before, during, and after PT; time needed for and sputum produced by each form of PT was recorded. PEP produced the highest amount of sputum, followed by PEP-AD, AD-PEP, and AD; all 4 forms of PT produced significantly more sputum than coughing. Lung function improved significantly after PEP, AD, and PEP-AD, but PEP-induced changes did not exceed those after AD. Within the investigated group, the PEP-induced lung function improvement per milliliter of sputum produced was significantly lower for those patients with airway hyperreactivity. The fact that the highest sputum yield with PEP was not reflected in higher PEP-effected lung function changes might thus be explained by PEP-induced bronchospasm in patients with airway hyperreactivity. PEP clears more sputum than AD or combined techniques; patients with airway hyperreactivity, however, should either prefer AD or should take a bronchodilator premedication before PEP.

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.

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance.

By opening up previously poorly ventilated lung regions, physiotherapy may either increase or decrease ventilation inhomogeneity; the short-term effect of physiotherapy on LCI appears to be unpredictable.

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BackgroundSARS-Co-V-2 infection in people with CF (pwCF) can lead to severe outcomes.MethodsIn 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.ResultsUp to 31 December 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% were admitted to hospital, 2.5% to intensive care. Regretfully 11 pwCF (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2–6-fold more frequent in lung-transplanted versus non-lung transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, CF-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).ConclusionSARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in one second (FEV1) <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.