Comparison of biosimilar Tigerase and Pulmozyme in long-term symptomatic therapy of patients with cystic fibrosis and severe pulmonary impairment (subgroup analysis of a Phase III randomized open-label clinical trial (NCT04468100))

Background Patients with cystic fibrosis (CF) need costly medical care and adequate therapy with expensive medicinal products. Tigerase® is the first biosimilar of dornase alfa, developed by the lead Russian biotechnology company GENERIUM. The aim of the manuscript to present post hoc sub-analysis of patients’ data with cystic fibrosis and severe pulmonary impairment of a larger comparative study (phase III open label, prospective, multi-centre, randomized study (NCT04468100)) of a generic version of recombinant human DNase Tigerase® to the only comparable drug, Pulmozyme® Methods In the analyses included subgroup of 46 severe pulmonary impairment patients with baseline FEV1 level 40–60% of predicted (23 patients in each treatment group) out of 100 patients registered in the study phase III open label, prospective, multi-center, randomized study (NCT04468100), and compared efficacy endpoints (FEV1, FVC, number and time of exacerbations, body weight, St.George’s Respiratory Questionnaire) as well as safety parameters (AEs, SAEs, anti-drug antibody) within 24 treatment weeks. Results All outcomes were comparable among the studied groups. In the efficacy dataset, the similar mean FEV1 and mean FVC changes for 24 weeks of both treatment groups were observed. The groups were also comparable in safety, all the secondary efficacy parameters and immunogenicity. Conclusions The findings from this study support the clinical Tigerase® biosimilarity to Pulmozyme® administered in CF patients with severe impairment of pulmonary function.

Growth Differentiation Factor 15 (GDF-15): A Novel Biomarker Associated with Poorer Respiratory Function in COVID-19

It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical and laboratory parameters reflecting severity in 84 patients with COVID-19, finding that GDF-15 levels were higher in both patients than in 20 healthy controls and were higher in patients with poorer respiratory function. GDF-15 levels also correlated with interleukin-6, C-reactive protein, ferritin and D-dimer levels and with neutrophilia and lymphopenia. Of all the analysed biomarkers, GDF-15 showed the best area under the receiver operating characteristics curve in identifying patients with poor respiratory function. In conclusion, our data support GDF-15 as a biomarker associated with pulmonary impairment in COVID-19 and so can potentially be useful in stratifying COVID-19 cases by severity.

Pulmonary Complication in Severe Malaria

Malaria is a potentially fatal disease caused by Plasmodium spp. Transmission occurs via the bite of female mosquito, Anopheles spp. Epidemiologically, global number of malaria patient are located in Southeast Asia and Africa. Until nowadays, millions of people still living in endemic area, with children and pregnant women are among the most vulnerable group in the population. Although there have been many advances in treatment and management, but the potential for harm remains; one of the example is lung involvement in patients with severe malaria. This paper aim to discuss briefly about lung derangement in the severe malaria and the inflammatory response related to the lung dysfunction. The severity of pulmonary impairment due to complications of malaria is determined not only by the initiation of antimalarial treatment but also by the hosts associated immune response.

Ventilatory limitations are not associated with dyspnea on exertion or reduced aerobic fitness in pectus excavatum: a critical information that must be highlighted to prevent inappropriate interventions.

Cover letter Pediatric Pulmonology Dear Editor, Enclosed is a manuscript to be considered in Pediatric Pulmonology that does not require an abstract , usually. This letter to the editor entitled “Ventilatory limitations are not associated with dyspnea on exertion or reduced aerobic fitness in pectus excavatum: a critical information that must be highlighted to prevent inappropriate interventions” comments the reports by Hardie and al. which tested the hypothesis that PEX deformities are associated with a pulmonary impairment during exercise and concluded that resting lung volume measurements were associated with the anatomic degree of PEX severity.

Preliminary results of clinical use of colchicine in COVID-19 treatment

We report a case of the use of colchicine in a patient infected with SARS-CoV-2 virus. A 37-year-old man with COVID-19 presented with moderate symptoms, mild pulmonary impairment and elevated inflammatory markers, suggesting an increased risk of cytokine storm and possible worsening of clinical condition. Experimental use of colchicine resulted in an 85% decrease in C reactive protein levels 3 days after treatment initiation and a 182.6% decrease in interleukin-6 levels 8 days after treatment initiation. Due to the lack of effective therapies, it is important to search for potential compounds and compounds that focus on controlling the danger caused by systemic inflammation in COVID-19. Although further research is needed in the area of colchicine and viral infection, preliminary efficacy was observed.

COVID-19: From viral infection to pulmonary failure

SARS-CoV-2 is a virus which promoted a worldwide pandemic outbreak in 2020. The virus is highly infectious and is able to contaminate a lot of people in a short time period. The disease promoted by the virus, named COVID-19, can cause different symptoms such as fever, cough, muscle pain, headache, prostration, diarrhea, neurological complications, dermic manifestations, pulmonary impairment, dyspnea, coagulopathies, organ failure, and death. Here, we show how the infection occurs and the major characteristics observed in the lungs of patients with COVID-19. In addition, we explored the immunological activation in this environment by the virus and some treatments used in the severe phase of the disease.