Introduction: Chronic Disease

There is no universal agreement on what constitutes a chronic disease; chronicity is a relative term that has shifted as advancements in medicine translate from bench to bedside, and focus of care moves from dealing with acute or terminal diagnoses to long-term management of chronic conditions [1]. Nevertheless, it is apparent that a crisis in chronic disease burden has emerged globally [2], and with it a body of literature for diseases that are now finding more commonalities under the umbrella of “chronic disease”. Within this new scope, are there parallel lessons broadly applicable for chronic disease? We present our June 2024 special issue of the Yale Journal of Biology and Medicine (YJBM) on Chronic Disease calling attention to underappreciated public health challenges faced by diverse communities, promising research and perspectives from clinicians and scientists, and growing global trends in the diagnosis and management of chronic disease.

Complex global healthcare challenges and more diversely represented populations in medicine have necessitated new integrated approaches to healthcare, with an ever-increasing appreciation for the patient perspective. Specifically, handling patient-provider relationships and patient education increasingly plays a critical factor in the delivery of positive outcomes and increased quality of life [3-5]. Patient disposition is examined by Buiting and Sonke, as well as Mete; both papers show how the pervasive nature of chronic disease leads to a patient’s mental health as a direct factor providers should consider and incorporate in the treatment of these conditions. Disposition additionally has a role in decision-making, which Boakye et al. connect by examining chronic kidney disease patients in Ghana to show how important facets of advanced care planning are impacted by these patients’ perspectives. A holistic approach to patient centric care can also extend trends seen with incorporation of digital technologies [6], in conjunction with traditional methods as explored in Khosla, Amin, and Doshi in their examination of the “barbershop intervention” strategy to patient education.

Fueled by increased chronic disease burden worldwide [2], the debate for clinicians on how to enhance patient care in the complex landscape of chronic diseases remains a pressing topic. Biological insights from immune disorders lead Parker et al. to argue for a more urgent call to action in follow-ups on several potential clinical leads and systemic improvements for effectively addressing environmental factors in chronic disease. These shifts in conceptual boundaries of chronic disease can additionally correct underdiagnosis or inadequate diagnosis, as Ribeiro et al. demonstrate with the incorporation of new technologies and a multitude of insights into dysfunctional joint patterns implicated in chronic conditions.

Given the increasing burden of chronic disease as a consequence of increasing longevity and new global paradigms [7,8], further progress on understanding disease mechanism is a necessity for better prevention and cost-effective treatment globally. Shanbhag and Bhowmik aptly review the role of aldo-keto reductases in various chronic diseases: the enzymatic promiscuity, functional diversity, and specificity of these enzymes that drive mechanisms underlying cataracts to those perpetuating common cancers. Furthermore, in an early stages review, Lee et al. detail the future avenues necessary to assess the potential of bioactive compounds from marine algae as disease-modifying therapeutics for Alzheimer’s disease. While current research does not yet support advancement to clinical trials, these works advance next steps in setting the framework for translation of candidate compounds to treatment of chronic disease [9]. Engaging in that next stage, Khan and Riaz et al. test a type 1 diabetes mellitus mouse model, illustrating the promise of treatments addressing peripheral neuropathy and cognitive impairment as a consequence of diabetes.

The examination of chronic disease continues into treatment models for diseases such as chronic rhinosinusitis and Alzheimer’s disease. Ghalehbaghi et al. demonstrate the possibility of targeted immunotherapies in T helper cell differentiation to alleviate chronic rhinosinusitis. With further contribution to recent cutting-edge research on the premise of rutin-based treatments for Alzheimer’s disease [10], Khan and Jatala et al. innovate with the use of carbon dots as nanocarriers enhancing the delivery of this paradigm-changing therapy.

From shifting high-level frameworks to the invigorating transformation of medicine in cutting-edge diagnostics and treatments, our YJBM June 2024 special issue on Chronic Disease presents a wide-angle lens snapshot of the field we feel matches the breadth of challenges arising from chronic disease. Our curation of manuscripts–some patient-focused and others clinician-focused, some investigating the mechanism of disease and others on therapeutic advances–aims to open the door for shared lessons across chronic disease, and we hope our readers find valuable insights within these works. We would also like to acknowledge the work of Peter Harris for the cover art; this piece reflects the challenging landscape patients face when burdened by chronic disease on their journey to meet with healthcare providers, and is a tribute to the strength required to surmount under-acknowledged obstacles on the route to seeking support.