American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2019
Review Comparative StudyCOPD Biomarkers and their Interpretation.
The pathology and impact of chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory process resulting in tissue damage with ineffective repair in response to toxic inhalants (especially cigarette smoke). Identification of mechanisms provides the opportunity to develop new therapies and a personalized approach to management. The collection of multiple genetic and detailed biochemical data from small and large patient cohorts has led to an explosion of studies investigating biomarkers to achieve these aims. ⋯ The present review assesses the importance of these associations, whether they represent cause or effect, reflect disease severity or activity, the complexity of the pathway to the final pathogenic and hence interventional step, and problems with interpreting cross-sectional studies without knowing individual disease trajectories. The complexity of biomarker specificity without sufficient clinical phenotype and endotype information contributes to problems of interpretation. A strategic change is needed to develop useful COPD biomarkers; this includes focusing on endotype biomarkers within specific clinical phenotypes, biomarkers in early COPD, exacerbation subtype biomarkers, and biomarkers to predict or measure drug effects.
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Am. J. Respir. Crit. Care Med. · May 2019
Tumor-Derived Autoantibodies Identify Malignant Pulmonary Nodules.
Rationale: Screening for non-small cell lung cancer is associated with earlier diagnosis and reduced mortality but also increased harm caused by invasive follow-up of benign pulmonary nodules. Lung tumorigenesis activates the immune system, components of which could serve as tumor-specific biomarkers. Objectives: To profile tumor-derived autoantibodies as peripheral biomarkers of malignant pulmonary nodules. ⋯ A combination of four of these autoantibodies could detect malignant nodules with an area under the curve of 0.74 and had an area under the curve of 0.78 in a subcohort of indeterminate (8-20 mm in the longest diameter) pulmonary nodules. Conclusions: Our novel pipeline identifies tumor-derived autoantibodies that could effectively serve as blood biomarkers for malignant pulmonary nodule diagnosis. This approach has future implications for both a cost-effective and noninvasive approach to determine nodule malignancy for widespread low-dose computed tomography screening.
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Am. J. Respir. Crit. Care Med. · May 2019
Identification and Modulation of Microenvironment is Crucial for Effective MSC Therapy in Acute Lung Injury.
Rationale: There are controversial reports on applications of mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). Objectives: We hypothesized that lung microenvironment was the main determinant of beneficial versus detrimental effects of MSCs during ARDS. Methods: Lung proteome was profiled in three models of injury induced by acid instillation and/or mechanical ventilation in mice. ⋯ Treatment with the inhibitory cocktail in samples of patients with ARDS retained protective effects of MSCs in small airway epithelial cells. Conclusions: MSCs can be beneficial or detrimental depending on microenvironment at the time of administration. Identification of potential beneficiaries seems to be crucial to guide MSC therapy in ARDS.