ERS International Congress 2021: highlights from the Paediatric Assembly

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection

RATIONALE: Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition. OBJECTIVES: To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa. METHODS: 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV(1))), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire—Revised (CFQ-R). RESULTS: The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV(1) was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs −0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV(1) improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49). CONCLUSIONS: Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection

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

Rehabilitation, Operation and Transfer of the Small Hydro Power Plants in the Republic of Macedonia

The paper presents an overview of the foreseen project ROT (Rehabilitation, Operation and Transfer) in the Republic of Macedonia. The ROT project include small hydro power plants (SHPP's) with ratings up to 5 MW: Dosnica, Sapuncica, Kalimanci, Pesocani, Pena, Matka and Zrnovci. The authors emphasized and discussed the main tasks and features of the ROT project for each plant and outlined the expected improvements of the functional and operational usage of the units in local distribution. The authors listed and comment the main objectives of the rehabilitation process such as availability, improvement of the operating and maintenance conditions, improvement of the entire plant performance and extending lifetime of equipment. The technological changes in control and communications of small hydro power plants and their implications in Macedonian power system are also presented and discussed. The complete scope of rehabilitation works is presented and the main and most interesting issues concerning operation and transfer of the plants

GENETIC MARKERS OF LOW BONE MINERAL DENSITY IN PATIENTS WITH CYSTIC FIBROSIS.

Introduction: failure to maintain bone mass density is a major problem in patients with cystic fibrosis (CF). CF is due to mutations in the CFTR gene and other genes may contribute to modifying the disease. Genetic and environmental factors may play a role in determining the variability of bone mass. Aim of the study: to analyse the association between polymorphic variants of genes considered to be risk factors of bone metabolism disturbances and decreased bone mineral density (BMD) in children and adults with CF in R. Macedonia. Materials and methods: the study included 80 clinically stable CF patients (age range 5-36y), who regularly attended the CF center at the Pediatric Clinic in Skopje, Macedonia. Three candidate genes likely associated with BMD variability were studied: the vitamin D receptor (VDR) gene, the estrogen receptor alpha (ESR1) and the type I alpha I collagen (COLIA1) gene. A complete bone and CF evaluation was obtained for all patients: 55 had normal BMD (group 1), 17 were osteopenic (group 2) and 8 were osteoporotic (group 3). Results: Low bone mineral density (Z score < -1SD) was found in 31.25% patients and in 10% of them BMD was below -2SD. Patients with low BMD had worse BMI, FEV1 and more severe symptoms of CF. No significant correlation was found between COLIA1 and VDR polymorphisms and BMD. Conclusion: There was no evidence that the genes under study may modulate bone phenotype in CF