Personalized Medicine in Idiopathic Pulmonary Fibrosis

Facts and Promises

Paolo Spagnolo; Argyris Tzouvelekis; Toby M. Maher


Curr Opin Pulm Med. 2015;21(5):470-478. 

In This Article

Abstract and Introduction


Purpose of review In this article, we summarize and discuss the most recent literature on personalized medicine in idiopathic pulmonary fibrosis (IPF), a chronic progressive and almost invariably lethal disease of unknown cause. This review is timely as major advances in our understanding of disease pathobiology and improvements in molecular techniques have recently led to the identification of potential surrogates of diagnosis, prognosis and response to treatment.

Recent findings The most promising and advanced candidate biomarkers are presented based on their proposed mechanistic pathways (e.g. alveolar epithelial cell dysfunction, immune dysregulation, microbiome, extracellular matrix remodeling and fibroproliferation, epigenetic markers and metabolomics). Recent data suggest that components of the immune system may contribute to the development of IPF. A potential role for infections as a cofactor in disease development and progression or as a trigger in disease exacerbation has also recently been proposed.

Summary Clinical management of IPF is unsatisfactory because of limited availability of truly effective therapies, lack of accurate predictors of disease behavior and absence of simple short-term measures of therapeutic response. A number of putative biomarkers have been identified in patients with IPF, although none has been validated to the standard necessary for their use in either therapeutic trials or clinical practice. Currently, ongoing prospective longitudinal studies will hopefully permit such validation.


Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and almost invariably fatal interstitial lung disease (ILD) of unknown cause for which there is no cure.[1–3] Patient management and clinical research in IPF pose a number of challenges, mainly related to incomplete knowledge of disease pathobiology and highly variable and unpredictable disease behavior, which make the optimal design and conduct of a clinical trial and the selection of the appropriate outcome measures problematic.[4]

The term 'personalized medicine' refers to a medical model, which aims, by using molecular profiling technologies, to customize healthcare (e.g. determining disease susceptibility, delivering timely prevention, predicting outcome and tailoring the right treatment for the right patient at the right time) at the level of the individual patient.[5] The first step in personalizing medicine is the identification of biomarkers, which, broadly speaking, can be defined as measurable factors (these are most often proteins, found in blood, body fluid or tissue but which can be physiological measures such as forced vital capacity [FVC] or imaging measures), which carry information about the health or disease state of the individual assayed.[6] IPF, like other complex, multipathway diseases, has the potential to benefit from developments in personalized care in several ways, including identification of individuals at risk, development of more accurate and less invasive diagnostic tools, improved understanding of the multitude of profibrotic pathways involved in disease biology, identification of therapeutic targets and improved early phase clinical trial design, prediction of outcome and prioritization of lung transplant and prediction of response to treatment (e.g. efficacy and toxicity markers). The availability of effective therapeutic options for patients with IPF makes the need for markers of diagnosis, prognosis and disease behavior greater than ever.[7–9]

In our review, we summarize and put into context the recent data on a number of promising candidate biomarkers. They are presented based on proposed mechanistic pathways.