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The role of precision medicine in interstitial lung disease.

ABSTRACT: The management of interstitial lung disease (ILD) may benefit from a conceptual shift. Increased understanding of this complex and heterogeneous group of disorders over the past 20 years has highlighted the need for individualised treatment strategies that encompass diagnostic classification and disease behaviour. Biomarker-based approaches to precision medicine hold the greatest promise. Robust, large-scale biomarker-based technologies supporting ILD diagnosis have been developed, and future applications relating to staging, prognosis and assessment of treatment response are emerging. Artificial intelligence may redefine our ability to base prognostic evaluation on both diagnosis and underlying disease processes, sharpening individualised treatment algorithms to a level not previously achieved. Compared with therapeutic areas such as oncology, precision medicine in ILD is still in its infancy. However, the heterogeneous nature of ILD suggests that many relevant molecular, environmental and behavioural targets may serve as useful biomarkers if we are willing to invest in their identification and validation.

SUBMITTER: Maher TM

PROVIDER: S-EPMC9449482 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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The role of precision medicine in interstitial lung disease.

Maher Toby M TM Nambiar Anoop M AM Wells Athol U AU

The European respiratory journal 20220907 3

The management of interstitial lung disease (ILD) may benefit from a conceptual shift. Increased understanding of this complex and heterogeneous group of disorders over the past 20 years has highlighted the need for individualised treatment strategies that encompass diagnostic classification and disease behaviour. Biomarker-based approaches to precision medicine hold the greatest promise. Robust, large-scale biomarker-based technologies supporting ILD diagnosis have been developed, and future ap ...[more]

PMID: 35115344

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Project description:ObjectiveThe aim of this study was to assess cardiovascular involvement in patients with connective tissue disease (CTD), and determine whether interstitial lung disease (ILD) in these patients is associated with elevated cardiovascular risk.MethodsThis study evaluated a retrospective cohort of 436 CTD patients admitted to a large teaching hospital in Zhejiang province, China, along with an additional 436 participants of an annual community health screening conducted in the physical examination center who served as age- and gender-matched controls. Demographic, clinical, serologic and imaging characteristics, as well as medications used by each participant were recorded. Cardiovascular involvement was defined by uniform criteria. Correlations between clinical/serologic factors and cardiovascular involvement were determined by univariate and multivariate analyses.ResultsCTD patients had a significantly higher cardiovascular involvement rate than controls (64.7% vs 23.4%), with higher rates of diabetes, hypertension, and hyperlipidemia, elevated systolic and diastolic pressures, C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol, and lower albumin and high-density lipoprotein cholesterol (all p < 0.05). Furthermore, CTP patients with cardiovascular involvement were significantly older, had higher systolic and diastolic pressures, C-reactive protein, glucose, and uric acid, higher rates of diabetes, hypertension, and use of moderate- to high-dose glucocorticoids, and longer disease duration compared to patients without involvement (all p < 0.05). Moreover, CTD in patients with cardiovascular involvement was more likely to be complicated by ILD (p < 0.01), which manifested as a higher alveolar inflammation score (p < 0.05). In the multivariate analysis, cardiovascular involvement in CTD patients was associated with age, systolic pressure, body mass index, uric acid, disease duration > 2 years, use of moderate- to high-dose glucocorticoids, and ILD with a high alveolar inflammation score.ConclusionCardiovascular involvement is increased in CTD patients, and is associated with ILD with a higher alveolar inflammation score. Thus, early-stage echocardiography and CT scans should be used to detect potential cardiovascular complications in these patients.

Project description:Glioblastoma (GBM) is a highly aggressive and heterogeneous form of brain cancer. Genotypic and phenotypic heterogeneity drives drug resistance and tumor recurrence. Combination chemotherapy could overcome drug resistance; however, GBM's location behind the blood-brain barrier severely limits chemotherapeutic options. Interstitial therapy, delivery of chemotherapy locally to the tumor site, via a biodegradable polymer implant can overcome the blood-brain barrier and increase the range of drugs available for therapy. Ideal drug candidates for interstitial therapy are those that are potent against GBM and work in combination with both standard-of-care therapy and new precision medicine targets. Herein we evaluated paclitaxel for interstitial therapy, investigating the effect of combination with both temozolomide, a clinical standard-of-care chemotherapy for GBM, and everolimus, a mammalian target of rapamycin (mTOR) inhibitor that modulates aberrant signaling present in >80% of GBM patients. Tested against a panel of GBM cell lines in vitro, paclitaxel was found to be effective at nanomolar concentrations, complement therapy with temozolomide, and synergize strongly with everolimus. The strong synergism seen with paclitaxel and everolimus was then explored in vivo. Paclitaxel and everolimus were separately formulated into fibrous scaffolds composed of acetalated dextran, a biodegradable polymer with tunable degradation rates, for implantation in the brain. Acetalated dextran degradation rates were tailored to attain matching release kinetics (~3% per day) of both paclitaxel and everolimus to maintain a fixed combination ratio of the two drugs. Combination interstitial therapy of both paclitaxel and everolimus significantly reduced GBM growth and improved progression free survival in two clinically relevant orthotopic models of GBM resection and recurrence. This work illustrates the advantages of synchronized interstitial therapy of paclitaxel and everolimus for post-surgical tumor control of GBM.

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The role of precision medicine in interstitial lung disease.

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The role of precision medicine in interstitial lung disease.

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