American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2024
Exploring Definitions and Predictors of Severe Asthma Clinical Remission Post-Biologic in Adults.
Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. ⋯ The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.
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Am. J. Respir. Crit. Care Med. · Oct 2024
Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.
Rationale: Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. Objectives: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. Methods: The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment. ⋯ At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4+ IFN-γ-positive SP-B-specific T cells and expanding T-cell clonotypes recognizing this protein, accompanied by a proinflammatory serum proteomic profile. Conclusions: Our data suggest that the cooccurrence of SP-B-specific immunoglobulin G autoantibodies and CD4+ T cells is associated with the development of pneumonitis during ICI therapy. Pretreatment levels of these antibodies may represent a potential biomarker for an increased risk of developing pneumonitis, and on-treatment levels may provide a diagnostic aid.
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Am. J. Respir. Crit. Care Med. · Oct 2024
Impact of Using Pre- and Post-Bronchodilator Spirometry Reference Values in a Chinese Population.
Rationale: Spirometry reference equations that are derived from a large, nationally representative general population are warranted in China, and the impact of using prebronchodilator (pre-BD) and post-BD spirometry reference values has yet to be assessed in Chinese populations. Objectives: To present the pre-BD and post-BD spirometry reference values for Chinese adults using the China Pulmonary Health (CPH) Study. Methods: A reference population of 17,969 healthy, nonsmoking participants in the CPH Study was used to calculate the pre- and post-BD reference values for FEV1, FVC, and FEV1/FVC ratio. ⋯ An additional 3.51% of participants were identified as having grade II-IV chronic obstructive pulmonary disease using the post-BD FEV1 predicted values. Conclusions: This study generated and applied pre- and post-BD spirometry reference values in a nationally representative Chinese adult population. Post-BD reference values may serve as an additional criterion in identifying individuals at risk for obstructive pulmonary diseases, and their diagnostic and prognostic values should be further investigated.
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Am. J. Respir. Crit. Care Med. · Oct 2024
Discovery of Two Novel Immunoepitopes and Development of Peptide-based Sarcoidosis Immunoassay.
Rationale: Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown, and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases. ⋯ Combining both biomarkers improved the area under the curve, sensitivity, specificity, and positive and negative predictive value. Conclusions: These results provide a novel immunoassay for sarcoidosis. The discovery of two neoantigens facilitates the development of biospecific drug discovery and the sarcoidosis-specific model.