Enhanced Stratification of IPF Patients Could Lead to Better Personalized Treatment

Patient stratification to deliver personalized medicine has become a routine practice in oncology that may be of great help in understanding and managing pulmonary diseases, such as idiopathic pulmonary fibrosis (IPF).

Supported by a deep understanding of a disease,  stratification is a process that categorizes patients into subgroups according to disease progression, individual biomarkers and distinct responses to therapy or predicted response to new treatments. Essentially, stratified medicine helps doctors provide the right treatment for individual patients at the right time.

Recently, a group of researchers at Royal Brompton and Harefield NHS Foundation Trust based in London,  provided an overview of the distinct molecular mechanisms involved in IPF, focusing particularly on those that may lead to improved diagnosis, stratification, and prediction of response to treatment, which may help managing patients and identifying new therapeutic targets in the future. The study, “Recent advances in understanding idiopathic pulmonary fibrosis,” was published in the journal F1000Research.

“It is becoming increasingly clear that genetic polymorphisms, whole blood transcriptomic profile, and lavage microbiome all predict groups of patients with differing disease behavior and outcomes and potentially variable responses to treatment.” the authors concluded in the article. “Considerable further research is required to deliver personalized medicine for IPF into the clinic, but at least now there is light at the end of what has been a very long tunnel.”

IPF is a chronic progressive disease that is often diagnosed through computed tomography (CT) scans and the patient’s clinical history. At times, lung biopsy may be required to confirm diagnosis, but it carries risks. The high heterogeneity found in IPF patients, including in their disease manifestations, progression, and in treatment response, has suggested that it is caused by distinct pathways, all controlled by a number of host and environmental factors, indicating that future IPF therapies will most likely focus on the combination of distinct drugs.

Usually, in the absence of a biopsy, early IPF is difficult to distinguish from other interstitial lung diseases (ILDs), and a doubt can exist even when a biopsy is available. The researchers believe that positron emission tomography (PET) and CT scans may improve the early detection of IPF and may be helpful in following disease activity and response to treatment, because both tests can detect highly metabolically active areas.

Currently, available medical measures do not allow an accurate prediction of how the disease will progress which highlights the need for the development of specific diagnostic and prognostic markers to  help guide treatment decisions. With the approval of pirfenidone (Esbriet) and nintedanib (Ofev), doctors need new markers able to predict how a patient is responding to a given drug, which could lead to a more personalized treatment.

Several of the patient’s clinical characteristics are predictors of worse prognosis. Older age, men gender, smoking history, low body mass index (BMI), pulmonary hypertension, and emphysema, are all predictors of poor survival rates. Changes in forced vital capacity, a measure of lung function, and in a 6-minute walking distance (6MWD) test also help doctors predict patient prognosis.

There are several candidate molecular biomarkers for IPF, including proteins that control gene expression, blood proteins, or bacteria in the lungs. Although IPF stratification based on molecular biomarkers is not yet available, advances are being made in that direction.

Similarly, some genetic variants from genes involved in host defense, cell adhesion, and DNA repair, have been associated with susceptibility to IPF and risk of disease progression. The genes include MUC5B, TOLLIP, SFTPC, SFTPA2, and TERP genes. Several genes and proteins are differentially expressed between IPF patients and healthy individuals, and even in patients with distinct disease severity. The identification of genes or proteins with diagnostic and prognostic value may be the first step towards the development of molecular tests for IPF patients, possibly through simple blood tests.