Facts and promises on lung biomarkers in interstitial lung diseases

Abstract

Interstitial lung diseases (ILDs) are a heterogeneous group of >100 pulmonary disorders. ILDs are characterized by an irreversible architectural distortion and impaired gas exchange; however, there is great variability in the clinical course. ILD diagnosis requires a combination of clinical data, radiological imaging and histological findings (when a lung biopsy is required). At the same time, successful management of ILD patients strictly depends on an accurate and confident diagnosis. In this context, the detection of reliable biomarkers able to identify ILD subtypes, avoiding lung biopsy, as well as the capacity to stratify patients and predict over time the disease course, has become a primary aim for all research studies in this field.

Keywords:

• circulating biomarkers
• epigenetics
• genes
• genome-wide analysis
• interstitial lung disease
• lung fibrosis
• miRNAs

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The ILDs are a heterogeneous group of pulmonary disorders affecting the parenchyma and spaces surrounding the alveoli.

• Circulating biomarkers mostly derive from damaged lung epithelium in ILD and reflect the severity of disease, but only a few biomarkers should be considered validated.

• Serum KL-6, MMP-7, CCL18 and YKL-40 seem to be the most promising serum biomarkers, but none of these is highly specific for ILD subtypes.

• Few studies attempt to drive therapeutic decisions based on serial biomarker measurement; the majority of published studies are still cross-sectional.

• Inherited ILD is based on the occurrence of familial genetic forms of disease. The pattern of inheritance is most frequently autosomal dominant, perhaps with reduced penetrance, even if autosomal recessive transmission has also been reported.

• It has been demonstrated that an SNP (rs35705950), in the promoter region of the MUC5B gene, is strongly associated with IPF and familial interstitial pneumonia.

• The development of sarcoidosis has been associated with the ‘8.1 ancestral haplotype’.

• The HLA gene region has also been identified as the most important genetic risk factor for SSc.

• Epigenetic studies on miRNA and ILDs have focused above all on lung fibrosis. Different expression of miRNAs has been demonstrated between IPF and normal lungs, and between rapidly progressing and slowly progressing IPF patients.

• In addition to microRNAs, a growing body of evidence suggests that lncRNAs regulate the respiratory phenotype. Thus changes in miRNA, long noncoding RNA and mRNA expression are likely to be of use as biomarkers for disease stratification and/or therapy follow-up.