American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2023
Autoantibody-mediated Macrophage Dysfunction in Severe Asthma Patients with Airway Infections.
Rationale: Localized autoimmune responses have been reported in patients with severe eosinophilic asthma, characterized by eosinophil degranulation and airway infections. Objective: To determine the presence of autoantibodies against macrophage scavenger receptors within the airways and their effects on macrophage function and susceptibility to infection. Methods: Anti-EPX (eosinophil peroxidase), anti-MARCO (macrophage receptor with collagenous structure) IgG titers, and T1 and T2 (type 1/2) cytokines were measured in 221 sputa from 143 well-characterized patients with severe asthma. ⋯ Patients with anti-MARCO antibodies had higher chances of subsequent infective versus eosinophilic exacerbations (P = 0.01). MDMs treated with immunoprecipitated immunoglobulins (anti-MARCO+ sputa) had reduced bacterial uptake by 39% ± 15% and significantly reduced release of IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.05) in response to an LPS stimulus. Conclusions: Autoantibodies against macrophage scavenger receptors in eosinophilic asthma airways may impede effective host defenses and lead to recurrent infective bronchitis.
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Am. J. Respir. Crit. Care Med. · Feb 2023
Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers.
Rationale: Children with preschool wheezing represent a very heterogeneous population with wide variability regarding their clinical, inflammatory, obstructive, and/or remodeling patterns. We hypothesized that assessing bronchial remodeling would help clinicians to better characterize severe preschool wheezers. Objectives: The main objective was to identify bronchial remodeling-based latent classes of severe preschool wheezers. ⋯ No significant differences were found between classes in the year before fiberoptic bronchoscopy. By contrast, Class BR1 was associated with a shorter time to first exacerbation and an increased risk of both frequent (3 or more) and severe exacerbations during the year after bronchoscopy in the two cohorts. Conclusions: Assessing bronchial remodeling identified severe preschool wheezers at risk of frequent and severe subsequent exacerbations with a favorable benefit to risk ratio.
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Am. J. Respir. Crit. Care Med. · Feb 2023
Plasticity of Individual Lung Function States from Childhood to Adulthood.
Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV1 z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (N = 3,069) were used. ⋯ The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.