Biomarkers in interstitial lung disease: moving towards composite indexes and multimarkers?

Abstract

Interstitial lung disease (ILD) covers a large spectrum of lung disorders that affects the parenchyma and is often associated with inflammation and/or fibrosis. Clinically, there is a great need for biomarker development for these disorders, to help diagnosis, treatment selection and assessment of efficacy as well as to predict progression. Thus far, no broadly validated biomarker exists for ILD, due to the existence of a very large number of disorders of often-unknown etiology, overlapping symptoms and disorders associated with a spectrum of multi-morbidities involving similar chronic inflammatory and fibrotic biochemical processes. We discuss here the development of biomarkers in IPF, sarcoidosis, connective tissue disease-associated ILD (CTD-ILD), and chronic hypersensitivity pneumonitis. We further discuss the need and opportunity to develop a multimarker approach that would be clinically meaningful for patients with ILD. Such composite index could include clinical symptoms, pathological assessment, and lung physiology measurements added to molecular information derived from bronchoalveolar lavage and serum. We also discuss the increased opportunity for patients to be involved in research as recent technological advances now allow the serial measurement of lung function using handheld spirometers, combined with handheld devices allowing measurement of patient reported outcomes, mobility, exercise, and sleep.

Diagnostic Role of Osteopontin in Interstitial Lung Disease

“…20 With the understanding of the basic cellular processes responsible for pulmonary fibrosis, numerous molecular biomarkers associated with disease progression have been identified, but clinical trials have yet to validate the clinical efficacy of these markers. 1 Research has revealed that OPN is highly expressed in lung diseases, and directly or indirectly involved in the regulation of granuloma formation and fibrosis. 21 In an experimental study on mice it was found that after exposure to titanium dioxide, mice not only develop a fibroproliferative lung disease, but also showed increased expression of OPN mRNA; and in turn increased levels of OPN in bronchoalveolar lavage fluid.…”

“…As a result of which, there is extensive tissue destruction leading to altered lung function; such as, restricted ventilation, hypoxemia, shortness of breath, exercise limitation and ultimately death from respiratory failure. 1,2 A large number of diffuse parenchymal lung disorders are grouped together as ILD, because of their common clinical, radiological and histopathological features. 3 ILD is composed of more than 200 recognized entities, classified into subtypes depending on their cause.…”

“…The commonly encountered subtypes are ILD due to connective tissue diseases, idiopathic pulmonary fibrosis (IPF), ILD due to inhaled substances, sarcoidosis and drug induced, among others. 1 In the diagnosis and categorization of various ILDs clinicians and researchers mainly depend on clinical data; for example, history and physical examination, radiological and pulmonary function tests, and histopathological patterns; these however, do not reflect the underlying pathobiological mechanisms of the disease. Moreover, these tests do not adequately sub-phenotype patients with ILD, who may have quantitatively or qualitatively different biological mechanisms responsible for their underlying disease.…”