A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma.

Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area.

Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program.

Extrapulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity. To determine if skeletal muscle adiposity predicts lung function trajectory in asthma. Adult SARP III (Severe Asthma Research Program III) participants with baseline computed tomography imaging and longitudinal postbronchodilator FEV% predicted (median follow-up 5 years [1,132 person-years]) were evaluated.

Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time.

Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time.

The Use of Targeted Monoclonal Antibodies in the Treatment of ABPA-A Case Series.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder occurring in response to that can complicate the course of asthma and cystic fibrosis. Here we present a case of acute ABPA without central bronchiectasis, a case of chronic active ABPA with central bronchiectasis, and a case of severe relapsing ABPA with central bronchiectasis. All three were initially treated with corticosteroids and antifungal agents but had an incomplete response.

A 33-Year-Old Man With Dyspnea, Chest Pain, and a Massive Pleural Effusion.

A 33-year-old white man presented to the ED with 1-month history of worsening dyspnea. He experienced gradual onset of right-sided scapular pain and shortness of breath on exertion that progressively worsened over the course of 1 month. He had a mild nonproductive cough and intermittent subjective fevers and reported weight loss of approximately 2 kg over 1 month.

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain. To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD. We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study.

Remote monitoring of oxygen saturation in individuals with COVID-19 pneumonia.

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Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.

Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1β secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1β in asthma is uncertain. To characterize the role of activated neutrophils in severe asthma through measurement of NETs and inflammasome activation.

Autopsy and Imaging Studies of Mucus in Asthma. Lessons Learned about Disease Mechanisms and the Role of Mucus in Airflow Obstruction.

Autopsy studies in fatal asthma have clearly documented the central role of airway plugging with pathologic mucus in the pathophysiology of death from asthma, but the role of mucus plugs in chronic severe asthma has been less well understood. Recently, multidetector computerized tomography imaging of the lungs has emerged as a valuable method to visualize mucus plugs in asthma. These multidetector computerized tomography data have revealed mucus plugs as a common occurrence in severe forms of asthma.

Seeing the forest for the trees: fractal dimensions measure COPD airway remodeling.

Chronic obstructive pulmonary disease (COPD) is extremely heterogenous in its effects on airway remodeling. Parsing the complex and interrelated morphologic changes and understanding their contribution to disease severity has posed a significant challenge to the field. In the current issue of the JCI, Bodduluri et al.

Neutrophil cytoplasts induce T17 differentiation and skew inflammation toward neutrophilia in severe asthma.

Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed.

Pruning of the Pulmonary Vasculature in Asthma. The Severe Asthma Research Program (SARP) Cohort.

Rationale: Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease.

Objectives: To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations.

Methods: We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5 mm in cross-sectional area (BV5) and of vessels less than 10 mm (BV10) in cross-sectional area on noncontrast computed tomographic scans of participants from the Severe Asthma Research Program.

Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.

Background: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain.

Objective: We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation.

Methods: We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85).

Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction.

Background: The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, and the role of eosinophils and their products in mucus plug formation is unknown.

Methods: In clinical studies, we developed and applied a bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans from 146 subjects with asthma and 22 controls, and analyzed relationships among mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophils. Additionally, we used airway mucus gel models to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups to promote mucus plug formation.

Association Between Insomnia and Asthma Burden in the Severe Asthma Research Program (SARP) III.

Background: Sleep difficulties are commonly reported by patients with asthma; however, the prevalence of insomnia and its association with disease burden and well-being is unknown. We aimed to determine the prevalence of insomnia, defined as combined sleep-specific complaints with associated daytime symptoms, among a large sample of adults with asthma, and to compare well-being, asthma control, and asthma-related health care utilization in individuals with asthma and insomnia and those without insomnia.

Methods: Baseline data from adults with physician-confirmed asthma enrolled in the Severe Asthma Research Program III was used for analyses (N = 714).

Biomarkers of Airway Type-2 Inflammation and Integrating Complex Phenotypes to Endotypes in Asthma.

Purpose Of Review: Over the past decade, the most important advance in the field of asthma has been the widespread recognition that asthma is a heterogeneous disease driven by multiple molecular processes.

Recent Findings: The most well-established molecular mechanism in asthma is increased airway type-2 inflammation, and consequently, non-invasive biomarkers of increased airway type-2 inflammation, such as blood eosinophil counts or blood periostin levels, have proven important in stratifying asthma patients in clinical trials of type-2 cytokine inhibitors. However, it remains ambiguous how well these non-invasive biomarkers represent airway measures of type-2 inflammation in asthma.

The Role of Type 2 Inflammation in the Pathogenesis of Asthma Exacerbations.

Asthma exacerbations are an important cause of asthma morbidity. Although viral infection of the upper airway is a common cause of asthma exacerbations, the reasons why some patients with asthma are exacerbation prone and others are exacerbation resistant are not fully understood. In this review, we examine whether Type 2 inflammation modifies airway function to make patients more susceptible to asthma exacerbations.