Airway remodeling in COVID-19 lungs

Besides parenchymal changes that have been described extensively in COVID-19, bronchiectasis is also reported but detailed characterization of airway changes is lacking. Hence, we aimed to quantify the number of visible airways and their diameters in end-stage COVID-19 lungs. Explanted right lungs, obtained after lung transplantation (n=2) or autopsy (n=1) (65.3+/-26.7 days after symptom onset), were inflated to total lung capacity, frozen and scanned with whole lung microCT (155 mum). Airways were segmented using Mimics Innovation Suite (Materialise, Belgium) and airway count and diameter were assessed using Neuronstudio. Three discarded donor lungs were used as controls. Number of visible airways increased in COVID-19 lungs compared to controls (fig.1a) potentially caused by airway remodeling and bronchiectasis (fig.1b, red arrows) due to fibrotic rearrangement (fig. 1b). Small airway count (diameter 0-2 mm) in generation (G) 1-11 was lower in COVID-19 patients compared to controls, with a shift of small airways from lower generations (G1-11) to higher generations (G12-27) in COVID-19 patients. Simultaneously, airways with a diameter > 2 mm were increased in all generations in COVID-19 (present until G21 compared to G13 in controls). This study shows that COVID-19 causes a remodeling of the (small) airways, leading to an increase of visible airways and diameter of large and small airways, similar to that seen in idiopathic pulmonary fibrosis due to traction bronchiectasis. (Figure Presented).

Epidemiology, Pathophysiology, and Pharmacological Status of Asthma

In India, asthma is a prevalent respiratory condition marked by frequent blowouts and a distinctive spread pattern. Respiratory diseases are the main cause of death globally. In India, asthma is more common, particularly in the North Indian states of Delhi and Uttar Pradesh. Our primary objective in this review is to study asthma medication therapy and its associated complications. The epidemiology, etiology, pathophysiology, mechanism of airway inflammation, classification, and diagnosis of asthma are all illustrated in the current work. Additionally, we have gathered state-by-state information on asthma for the last five years in Northern India. Asthma diagnosis and management are also discussed in accordance with the guidelines of many agencies, including NICE, BTS, SIGN, and WHO. Copyright © 2022 Bentham Science Publishers.

Recent advances in the immunopathogenesis of severe asthma.

Severe asthma is a heterogeneous disease encompassing different phenotypes and endotypes. Although patients with severe asthma constitute a small proportion of the total population with asthma, they largely account for the morbidity and mortality associated with asthma, indicating a clear unmet need. Being distinct from mild and moderate disease, new insights into the immunopathogenesis of severe asthma are needed. The disease endotypes have provided better insights into the immunopathogenic mechanisms underlying severe asthma. Current stratified approach of treating severe asthma based on phenotypes is met with shortcomings, necessitating unbiased multidimensional endotyping to cope with disease complexity. Therefore, in this review, we explore the distinct endotypes and their mechanistic pathways that characterize the heterogeneity observed in severe asthma.

Monocyte-derived macrophages display an inflammatory memory several months post-SARS-CoV- 2 infection

Background: Monocytes and macrophages drive the inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) and they are a major source of eicosanoids in airway inflammation. Method: We used RNA sequencing and LC-MS/ MS analysis to determine transcriptional and lipid mediator profiles of monocyte-derived macrophages from convalescent COVID-19 patients 3-5 months post-SARS- CoV- 2 infection. Results: We found that monocyte-derived macrophages (MDM) from SARS-CoV- 2- infected individuals with mild disease show an inflammatory transcriptional and metabolic imprint several (3-5) months after SARS-CoV- 2 infection. MDM from convalescent SARS-CoV- 2- infected individuals showed higher expression of fatty acid-metabolic enzymes and increased production of pro-inflammatory eicosanoids, particularly neutrophil chemotactic leukotriene B4 (LTB4) and LTD4 a driver of airway remodeling. MDM from previously SARS-CoV- 2- infected subjects showed an exaggerated induction of inflammatory chemokines as well as T-cell suppressive enzymes and receptors following stimulation with spike protein or LPS. Corticosteroids reduced inflammatory cytokine-, but increased leukotriene production in macrophages. Conclusion: Thus, SARS-CoV- 2 infection leaves an inflammatory imprint in the monocyte/macrophage compartment that drives aberrant effector functions and eicosanoid metabolism, possibly explaining long-term effects in patients recovering from mild COVID-19.