Severe coronavirus disease (COVID‐19) is characterized by an excessive proinflammatory cytokine storm, resulting in acute lung injury and development of acute respiratory distress syndrome (ARDS). ...The role of corticosteroids is controversial in severe COVID‐19 pneumonia and associated hyper‐inflammatory syndrome. We reported a case series of six consecutive COVID‐19 patients with severe pneumonia, ARDS and laboratory indices of hyper‐inflammatory syndrome. All patients were treated early with a short course of corticosteroids, and clinical outcomes were compared before and after corticosteroids administration. All patients evaded intubation and intensive care admission, ARDS resolved within 11.8 days (median), viral clearance was achieved in four patients within 17.2 days (median), and all patients were discharged from the hospital in 16.8 days (median). Early administration of short course corticosteroids improves clinical outcome of patients with severe COVID‐19 pneumonia and evidence of immune hyperreactivity.
Research Highlights
Severe COVID‐19 is characterized by an excessive pro‐inflammatory cytokine storm resulting in acute lung injury and development of ARDS.
Early, short‐course of corticosteroids in severe COVID‐19 pneumonia and associated hyper‐inflammatory syndrome may be beneficial.
Routine use of corticosteroids in COVID‐19 is not recommended.
Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ...‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.
This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence ...relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL
to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL
) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4-5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
The European Respiratory Society (ERS) Presidential Summit is an annual event in the diary of the ERS President and the ERS leadership. It is an occasion where the ERS President can select a topic of ...relevance to the respiratory field, but one that has a more societal focus and one that transcends boundaries between diseases. The summit has the scope of raising awareness about lung health and disease, building alliances and helping promote better health. It allows the leadership of the ERS, as well as key stakeholders in health, to look at an issue from a wider perspective, to learn from other disciplines, and to discuss and debate.
The ERS Presidential Summit is an annual event in the diary of the ERS President and leadership. The summit has the scope of raising awareness about lung health and disease, building alliances and helping better health.
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In daily clinical practice, radiologists and pulmonologists are faced with incidental radiographic findings of pulmonary nodules. Deciding how to manage these findings is very important as many of ...them may be benign and require no further action, but others may represent early disease and importantly early-stage lung cancer and require prompt diagnosis and definitive treatment. As the diagnosis of pulmonary nodules includes invasive procedures which can be relatively minimal, such as bronchoscopy or transthoracic aspiration or biopsy, but also more invasive procedures such as thoracic surgical biopsies, and as these procedures are linked to anxiety and to cost, it is important to have clearly defined algorithms for the description, management, and follow-up of these nodules. Clear algorithms for the imaging protocols and the management of positive findings should also exist in lung cancer screening programs, which are already established in the USA and which will hopefully be established worldwide. This article reviews current knowledge on nodule definition, diagnostic evaluation, and management based on literature data and mainly recent guidelines.
Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition ...and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the ...airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes.
Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous ...spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best‐defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non‐type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point‐of‐care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out ...priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer care but are associated with unique adverse events, including potentially life-threatening pneumonitis. The diagnosis of ICI-pneumonitis ...is increasing; however, the biological mechanisms, clinical and radiologic features, and the diagnosis and management have not been well defined.
To summarize evidence, identify knowledge and research gaps, and prioritize topics and propose methods for future research on ICI-pneumonitis.
A multidisciplinary group of international clinical researchers reviewed available data on ICI-pneumonitis to develop and refine research questions pertaining to ICI-pneumonitis.
This statement identifies gaps in knowledge and develops potential research questions to further expand knowledge regarding risk, biologic mechanisms, clinical and radiologic presentation, and management of ICI-pneumonitis.
Gaps in knowledge of the basic biological mechanisms of ICI-pneumonitis, coupled with a precipitous increase in the use of ICIs alone or combined with other therapies, highlight the importance in triaging research priorities for ICI-pneumonitis.
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