Raksha Jain | Professor of Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Department of Internal Medicine, Dallas, Texas, USA
Citation: Respir AMJ. 2026; https://doi.org/10.33590/respiramj/2HR20X68
Congratulations on receiving the American Thoracic Society (ATS) John W. Walsh Award. Looking across your career, which scientific contribution or line of investigation do you believe has had the greatest impact on the cystic fibrosis (CF) field, and why?
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have had the greatest impact on the CF field because they have fundamentally changed the lives of many people with CF. These therapies have improved lung function, quality of life, and projected survival, while not adding to treatment burden compared with many traditional nebulized therapies. Their development has transformed CF from a disease managed primarily through supportive care to one where the aim is treating the underlying protein defect.
We are now in an era where highly effective CFTR modulators have fundamentally altered the natural history of CF. How has this shift changed the most pressing research questions facing the field?
Although highly effective CFTR modulators have transformed CF care, several critical questions remain. Some people with CF are not eligible for modulators, cannot tolerate them, or lack access to these therapies, and they remain an especially important group for future research. In addition, many individuals who are taking modulators continue to experience pulmonary exacerbations, persistent symptoms, infections, inflammation, or extrapulmonary complications. The field now needs to focus not only on extending access to CFTR-directed therapies, but also on understanding residual disease and developing complementary treatments.
As patients live longer and experience improved lung function, what emerging complications or unmet needs are becoming increasingly apparent in clinical practice?
With all success comes some challenges. We are entering a new era of understanding aging in CF. Clinicians and researchers now need to address questions that historically received less attention, including malignancy risk, particularly gastrointestinal cancers, cardiovascular and metabolic disease, osteoporosis, menopause, and other age-related complications. These issues underscore the need to broaden CF care beyond pulmonary outcomes and focus on long-term health across the lifespan.
Many pivotal questions in CF today concern what happens after successful restoration of CFTR function. To what extent can existing structural lung damage, inflammation, and infection be reversed, and where are the biggest knowledge gaps?
Many people with CF continue to have persistent structural lung disease, symptoms, infection, inflammation, and pulmonary exacerbations despite CFTR modulator therapy. A major knowledge gap is understanding which aspects of established lung disease are reversible, and which require additional targeted therapies. Another key challenge is determining the best tools to evaluate new treatments, because forced expiratory volume in 1 second may no longer be sensitive enough as a primary endpoint to develop new therapies. We will likely need complementary or composite endpoints that better capture inflammation, infection, structural disease, symptoms, and quality of life.
Some individuals continue to derive limited benefit from currently available CFTR modulators. What therapeutic strategies do you believe hold the greatest promise for these patients over the next decade?
Therapeutic strategies are needed for individuals who do not benefit sufficiently from current CFTR modulators. Nucleic acid-based therapies that are independent of the underlying CFTR variant are particularly promising because they could potentially benefit all people with CF. Anti-inflammatory therapies also remain important, especially for individuals with persistent airway inflammation. In addition, we need better approaches to chronic infection beyond traditional antimicrobials, including strategies such as phage therapy and gallium-based therapies. Improved treatments for CF-related diabetes and other extrapulmonary complications will also be essential. These approaches are complementary, and many will likely have an important role in the future of CF care.
Your work has explored sex- and gender-related differences in airway disease. What biological mechanisms do you believe are driving these disparities, and are we close to translating these findings into personalised approaches to care?
Across CF and other airway diseases, including bronchiectasis, COPD, and asthma, females often experience worse outcomes, particularly higher rates of pulmonary exacerbations. I suspect there may be shared biological mechanisms across these diseases, potentially related to neutrophilic inflammation, hormonal influences, immune responses, and airway microbiology. Our research group is working to better understand these mechanisms, with the goal of identifying pathways that could eventually support sex-based personalized approaches to care.
As Chair of the Cystic Fibrosis Foundation (CFF)’s Sexual Health, Reproduction, and Gender Research Working Group, how do you see reproductive and sexual health considerations reshaping the way we think about long-term CF management?
I served as Chair of the CFF-supported SHARING Working Group for the past 3 years, which gave me the opportunity to collaborate with researchers and people with CF across the country. Reproductive and sexual health considerations are becoming increasingly important as more people with CF are living longer, healthier lives. We have seen a dramatic increase in pregnancies among females with CF, and many males and females have important questions about fertility, pregnancy, parenthood, and the potential impact on their own health and the health of their children. These issues need to be integrated into routine, long-term CF care.
With increasing survival, more patients are navigating adulthood, parenthood, and aging with CF. How should research priorities evolve to reflect these changing patient experiences?
Research priorities should be guided by the lived experiences and priorities of people with CF. For many individuals, the most important issues may extend beyond lung disease and include gastrointestinal health, diabetes, reproductive health, mental health, menopause, parenting, employment, and aging. Living longer is an important goal, but living well is equally important. The next phase of CF research should therefore focus on quality of life, whole-person health, and outcomes that reflect what matters most to people with CF.
