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Press Releases

Take a look at a selection of our recent media coverage:

Severity of systemic sclerosis-associated interstitial lung disease linked to adipokine level

11th August 2021

Reduced pulmonary function in systemic sclerosis-associated interstitial lung disease was linked to higher levels of an adipokine biomarker.

Systemic sclerosis can be defined as a systemic connective tissue disease. It is characterised by small vessel vasculopathy, production of autoantibodies and dysfunctional fibroblasts, with an increased deposition of extracellular matrix. In a UK study, the prevalence of systemic sclerosis was estimated to be 19.4 per million person-years and 4.7 times more common in women. In contrast, a US study estimated prevalence of 50 – 300 cases per million. Clinically, patients present with skin thickening, Raynaud’s syndrome and polyarthralgia. Fibrosis of the lung is known to be a complication of systemic sclerosis, leading to systemic sclerosis-associated interstitial lung disease (SS-ILD) and pulmonary hypertension. The presence of system sclerosis reduces life-expectancy by 16 to 34 years and studies suggest that SS-ILD is associated with a 2.6 greater increased risk of death. However, there is a lack of data on potential biomarkers of lung function, hindering the assessment of current and future disease progression.

Some work has revealed an accumulation of myofibroblasts in fibrotic skin in patients with systemic sclerosis and a loss of intradermal adipose tissue. Furthermore, patients with systemic sclerosis have been found to have lower levels of serum adiponectin, a hormone secreted by adipose tissue. Other data has suggested that one particular adipokine, CTRP9 is elevated in patient with patients with systemic sclerosis. This led a team from the Department of Medicine, Division of Rheumatology, University of California, US, to examine whether CTRP9 could serve as a biomarker with predictive valve for pulmonary function in patients with SS-ILD. The team turned to a patient registry to retrospectively examine this relationship and included patients with documented pulmonary tests over a 48-month interval and where CTRP9 levels had been initially recorded. They split patients into a high and low group according to CTRP9 levels and set the primary outcome of interest as forced vital capacity percent predicted (FVC%), which is valid measure of disease severity in SS-ILD.

Findings
A total of 61 patients with a mean age of 53.5 years (77.3% female) were included in the analysis. Elevated circulating CTRP9 levels were associated with significantly lower FVC% levels at baseline (72% vs 80%, p = 0.02) and after 48 months (68% vs 84%, p = 0.001). In addition, the researcher sought to determine whether CTRP9 levels could predict disease stability, which they defined as less than 3% decrease in FVC% over 48 months. The analysis showed that a low baseline CTRP9 level had a sensitivity of 73% and a specificity of 45% for disease stability.

The authors discussed how their findings clearly indicated that the presence of elevated CTRP9 was associated with more severe lung disease. They concluded that CTRP9 could represent a prognostic biomarker and a possible therapeutic target for SS-ILD.

Citation
Yang MM et al. Circulating CTRP9 is associated with severity of systemic sclerosis-associated interstitial lung disease. Arthritis Care Res 2021

Serum molecules differentiate types of interstitial lung disease

5th August 2021

In patients with interstitial lung disease, a combination of serum molecules served as a differential diagnostic biomarker.

The term interstitial lung disease (ILD) is an umbrella term to describe a group of diseases all of which are characterised by inflammation or fibrosis of the alveolar wall and impairment of gas exchange. One form of ILD is connective tissue disease-associated ILD (CTD-ILD) and which occurs in patients with a connective tissue disease such as Sjogren’s syndrome, systemic lupus erythematosus and polymyositis, with an estimated incidence of 15% of the population. Other forms of ILD include idiopathic pulmonary fibrosis (IPF) and which has an estimated worldwide prevalence of 13 to 20 cases per 100,000. The diagnosis of ILD and identification of the underlying cause can be challenging and relies upon a combination of blood, imaging and pulmonary function tests.

The precise cause of ILD is unclear although proposed aetiologies have included an imbalance between oxidant-antioxidant factors, particularly in idiopathic pulmonary fibrosis as well as an increased level of advanced glycation end-products (AGE). Furthermore, increased levels of matrix metalloproteinase-7 (MMP-7) is also involved as witnessed by elevated levels in those with IPF. Nevertheless, differentiating between CTD-ILD and other forms of ILD such as IPF is important because the treatment is different. This led a team from the Respiratory Service, University of Virgen de la Victoria Hospital, Malaga, Spain, to explore whether it was possible to use several serum molecules to differentiate between IPF and CTD-ILD. The team recruited patients with both IPF and CTD-ILD and after a single visit to the hospital, blood samples were taken together and the levels of AGE, advanced oxidation protein products (AOPP) and MMP-7 determined. The performance of each marker was assessed using the area under the receiver operating characteristic curve (AUC) and used to determine the sensitivity and specificity of each biomarker.

Findings
In total there were 73 patients, 29 with IPF and 14 CTD-ILD and 30 healthy controls. The average age of participants was not significantly different and approximately 63 years. Mean levels of AGE, AOPP and MMP-7 were all elevated in both the CTD-ILD and IPF groups compared to controls. The AUC for AGE was 0.78 (95% CI 0.60–0.97) for patients with IPF, 0.80 for AOPP and 0.96 for MMP-7. In addition, the AUC for AGE was higher for CTD-ILD than for IPF (0.95, 95% CI 0.86 – 1.0). Using MMP-7 as a biomarker, for both conditions, the sensitivity was 92.3% for IPF and 100% for CTD-ILD and the corresponding specificities were both 92.9%. However, combining the biomarkers, AGE and MMP-7, increased the sensitivity for distinguishing between IPF and CTD-ILD to 93.3% and the specificity 100%.

In their discussion, the authors noted that while all three biomarkers were elevated in patients with the different forms of ILD, the combination of two of these markers (MMP-7 and AGE) was able to differentiate between the CTD-ILD and IPF and might therefore serve as an important biomarker in clinical practice.

Citation

Cesae EC et al. Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease. J Clin Med 2021