Dr. Victor Ortega: Genetic testing aids in diagnosing idiopathic pulmonary fibrosis
Dr. Wala' Hafez notes that idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that leads to the gradual scarring of lung tissue, thereby impairing its primary function of delivering oxygen to the body. Because its early symptoms resemble those of common respiratory conditions, diagnosis can be delayed, highlighting the importance of paying attention to persistent shortness of breath and dry cough, as well as seeking early medical evaluation. Recently, researchers have validated a genetic risk assessment tool that may help physicians diagnose IPF and identify patients at higher risk for severe complications, including death or the need for lung transplantation. The findings come from a new international study involving more than 570,000 individuals, conducted under the joint leadership of Mayo Clinic and Brigham and Women’s Hospital.
A Landmark Study
The study, published in the American Journal of Respiratory and Critical Care Medicine, is among the largest to evaluate, in real-world clinical settings, the genetic risk scores for IPF. The results bring the application of genetic analysis closer to routine medical care. Researchers analyzed genetic data and electronic health records from four biobanks in the United States and the United Kingdom, including the Mayo Clinic Biobank and “Mayo Clinic Tapestries.” They calculated a genetic risk score for each participant by aggregating the effects of more than 60,000 genetic variants associated with IPF. The results showed that while each individual variant has a small effect on risk, the collective impact of these variants reveals a genetic susceptibility to the disease that is difficult to detect by other means.
Subsequently, the researchers tested the ability of these risk scores to identify individuals with the disease and predict their health outcomes. Individuals with high genetic risk scores were approximately three times more likely to develop the disease compared to those with low scores. Furthermore, the predictive accuracy of the disease improved when using more specific diagnostic definitions, suggesting that these scores may help in the future to distinguish IPF from other forms of interstitial lung disease. Among those diagnosed with the disease, patients with high genetic risk were 23% more likely to experience death or require lung transplantation, indicating that these scores may help identify patients most vulnerable to adverse outcomes.
A Unique Genetic Fingerprint
Victor Ortega, a pulmonologist and Associate Director of the Mayo Clinic Center for Individualized Medicine in Arizona, and one of the study’s co-lead authors, stated: “Every patient has a unique genetic fingerprint that we can leverage to estimate their risk of developing the disease. Polygenic risk scores add a new dimension to our understanding of IPF and mortality rates, bringing us closer to a future where diagnosis, disease trajectory prediction, and treatment are guided by each patient’s unique molecular profile.”
IPF causes irreversible scarring in the lungs, progressively limiting a person’s ability to breathe. More than 100,000 Americans live with this condition, and an estimated 30,000 to 40,000 new cases are diagnosed annually, according to the National Institutes of Health.
Similar Symptoms
Due to the similarity of its symptoms with those of other interstitial lung diseases, diagnosis may be delayed until the lungs are severely and irreversibly damaged. Confirming the diagnosis often requires a lung biopsy to obtain a tissue sample. Researchers hope that the development of a non-invasive genetic test using DNA extracted from blood or saliva samples will reduce the need for surgical procedures in some patients.
Christopher Grillo, PharmD, a researcher at the Mayo Clinic Center for Individualized Medicine and co-first author, said: “Most polygenic risk scores are validated in carefully selected research cohorts. Demonstrating the effectiveness of this approach in more than half a million individuals receiving routine clinical care is a significant step toward understanding how patients can ultimately benefit from it.”
Researchers anticipate that if these scores are validated through further studies, they could enhance the results of imaging tests and other diagnostic tools, helping physicians diagnose the disease with greater confidence.
Early Prevention
This research aligns with the Precure (Prevention and Cure) research initiative launched by Mayo Clinic, which aims to detect early biological changes associated with diseases and translate these discoveries into clinical tools that improve diagnosis and personalize healthcare for each patient, potentially altering the course of the disease. As part of this effort, the “Early Detection of Lung Diseases” study, led by Dr. Ortega, is being expanded under the Precure initiative.
