Serum biomarkers of remodeling in severe asthma with fixed airway obstruction and the potential role of KL-6.

Over 3% of asthmatic patients are affected by a particularly severe form of the disease ("severe asthma", SA) which is often refractory to standard treatment. Airway remodeling (AR), which can be considered a critical characteristic of approximately half of all patients with SA and currently thought to be the main mechanism triggering fixed airway obstruction (FAO), seems to be a key factor affecting a patient's outcome. Despite the collective efforts of internationally renowned experts, to date only a few biomarkers indicative of AR and no recognizable biomarkers of lung parenchymal remodeling have been identified. This work examines the pathogenesis of airway and lung parenchymal remodeling and the serum biomarkers that may be able to identify the severe asthmatic patients who may develop FAO. The study also aims to examine if Krebs von den Lungen-6 (KL-6) could be considered a diagnostic biomarker of lung structural damage in SA.

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Severe Asthma, Telemedicine, and Self-Administered Therapy: Listening First to the Patient.

Severe asthma patients are at an increased risk of major complications and they need to be monitored regularly. The COVID-19 pandemic has notably impacted on the health care resources. The telemedicine approach applied to the follow-up of asthmatic patients has been proven to be effective in monitoring their disease and their adherence to the therapy. The aim of our study was to investigate the satisfaction of severe asthma patients before the activation of a telemedicine management, as well as their current experience with self-administration of injection therapy. An ad hoc questionnaire was developed and sent by e-mail to 180 severe asthma patients. Most of subjects, 82%, were confident with the idea of doing self-measurements and self-managing their disease. Further, 77% of subjects favoured to carry out virtual visits and telemedicine. Regarding the home treatment, 93% of patients considered the self-injection therapy easy, 94% of subjects felt safe, and 93% were not worried while self-administering. Only mild adverse events were reported in 22% of patients after self-administration. Our results showed an agreement between what is considered necessary and practicable by healthcare personnel and what is perceived by the severe asthma patients in terms of treatment and monitoring of the disease with Telehealth. Biologics have a safety profile and can be easily self-administred at home.

Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses.

The most common hereditary disorder in adults, α1-antitrypsin deficiency (AATD), is characterized by reduced plasma levels or the abnormal functioning of α1-antitrypsin (AAT), a major human blood serine protease inhibitor, which is encoded by the SERine Protein INhibitor-A1 (SERPINA1) gene and produced in the liver. Recently, it has been hypothesized that the geographic differences in COVID-19 infection and fatality rates may be partially explained by ethnic differences in SERPINA1 allele frequencies. In our review, we examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates. Moreover, we described shared pathogenetic pathways that may provide a theoretical basis for our epidemiological findings. We also considered the potential use of AAT augmentation therapy in patients with COVID-19.