The Expanding Role of Biomarkers in the Assessment of Smoking-Related Parenchymal Lung Diseases

Doyle, Tracy J.; Pinto-Plata, Víctor; Morse, Danielle; Celli, Bartolomé R.; Rosas, Iván O.

doi:10.1378/chest.12-1540

Cited by 35 publications

(20 citation statements)

References 67 publications

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“…Second, although our findings suggest that clinical risk factors and autoantibodies alone may identify the presence of RA-ILD in two independent cohorts, it is possible that the performance of these risk factors will decrease in a larger cohort, particularly when age, RF, and anti-CCP are stratified and incorporated into a clinical prediction model. Third, although the investigational biomarker signature (MMP7, PARC, and SP-D) was tested in an independent cohort, there are limitations of validity inherent to all experimental biomarkers, especially reproducibility and generalizability (51). Additional studies should be conducted to determine the ability of this combinatorial signature to correlate with meaningful clinical outcomes.…”

Section: Diagnostic Test For the Identification Of Subclinical Ra-ildmentioning

confidence: 99%

Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

Doyle

Patel

Hatabu³

et al. 2015

Am J Respir Crit Care Med

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183

132

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Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized.Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD.Methods: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results:A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD.Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.Keywords: interstitial lung disease; rheumatoid arthritis; subclinical; biomarkers; risk prediction

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Section: Diagnostic Test For the Identification Of Subclinical Ra-ildmentioning

confidence: 99%

Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

Doyle

Patel

Hatabu³

et al. 2015

Am J Respir Crit Care Med

Self Cite

183

132

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“…The benefit of an individual biomarker as a diagnostic tool remains questionable: to date, the majority of biomarkers proposed do not allow the discrimination between different ILDs and they have poor specificity for IPF. Besides these considerations, which are an issue for biomarker studies in general [54,104], there are some limitations in the use of these biomarkers derived from injured epithelial cells (i.e. from epithelial cell breakdown or hyperplasia).…”

Section: Discussionmentioning

confidence: 99%

“…Special attention has been given to the peripheral blood protein markers. They present advantages over the other compartment as they are minimally invasive and readily available in clinical settings, and can easily be measured longitudinally and during exacerbations (for excellent review on the different types of pulmonary biomarkers and existing limitations, see Doyle et al [54]).…”

Section: Monitoring the Disease: Insights From The Bench Sidementioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: From Epithelial Injury to Biomarkers - Insights from the Bench Side

Borensztajn

Crestani²,

Kolb³

2013

Respiration

110

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Idiopathic pulmonary fibrosis (IPF) is the most frequent fibrotic diffuse parenchymal lung disease. Its prognosis is devastating: >50% of the patients die within 3 years after diagnosis. Options for the treatment of IPF are limited and lung transplantation is the only ‘curative' therapy. Currently, in the absence of validated indicators of disease progression/activity and diagnostic tools, the clinical management of IPF remains a major challenge. A better understanding of the pathogenesis of IPF is critical for the identification of new therapeutic targets as well as molecules that may serve as surrogate markers for clinically significant endpoints. The current paradigm on the mechanisms leading from a normal to a fibrotic lung postulates that chronic epithelial lesion leads to aberrant wound healing activation, which is characterized by deregulated fibroblast proliferation and activation together with an uncontrolled extracellular matrix synthesis. In this review, we shed light on the role of epithelial cell damage in the pathogenesis of fibrosis. Finally, we examine the markers of epithelial damage and their potential use as biomarkers and the future of this continuously expanding field.

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“…Lung-based protein biomarkers can be detected in the peripheral blood, but, although some biomarkers have been shown to correlate with disease progression and survival, the use of biomarkers in IPF remains experimental (89)(90)(91). Several peripheral blood biomarkers have been independently validated in the research setting, and should be investigated as potential riskstratification tools (92)(93)(94).…”

Section: Recommendations For Primary Prevention Researchmentioning

confidence: 99%

Interstitial Lung Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

et al. 2014

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Population-based, longitudinal studies spanning decades linking risk factors in childhood, adolescence and early adulthood to incident clinical interstitial lung disease (ILD) events in late adulthood have not been performed. In addition, no observational or randomized clinical trials have been conducted; therefore, there is presently no evidence to support the notion that reduction of risk factor levels in early life prevents ILD events in adult life. Primary prevention strategies are host-directed interventions designed to modify adverse risk factors (i.e., smoking) with the goal of preventing the development of ILD, whereas primordial prevention for ILD can be defined as the elimination of external risk factors (i.e., environmental pollutants). As no ILD primary prevention studies have been previously conducted, we propose that research studies that promote implementation of primary prevention strategies could, over time, make a subset of ILD preventable. Herein, we provide a number of initial steps required for the future implementation of prevention strategies; this statement discusses the rationale and available evidence that support potential opportunities for primordial and primary prevention, as well as fertile areas for future research of preventive intervention in ILD.

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The Expanding Role of Biomarkers in the Assessment of Smoking-Related Parenchymal Lung Diseases

Cited by 35 publications

References 67 publications

Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

Idiopathic Pulmonary Fibrosis: From Epithelial Injury to Biomarkers - Insights from the Bench Side

Interstitial Lung Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

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