Diagnosing Uncertainty: Cystic Fibrosis, Disease Definitions, and Diagnostic Challenges in Medicine

Abstract

This dissertation examines why diagnostic uncertainty persists in medicine and the impact of such uncertainty on patients and families. Using cystic fibrosis (CF) as a case study, this work explores the unexpectedly complex relationship between diagnostic tests and disease concepts, examines the performance of tests as tools to diagnose patients, and interrogates the priority physicians place on test results versus patient accounts in determining a diagnosis. Drawing from archival sources, oral history interviews, newspaper accounts, and the medical and scientific literature, the dissertation demonstrates that technological advances have not led to the increased certainty in diagnosis that many physicians expected. Using a specific diagnostic technology as a starting point for each chapter, the dissertation documents the many sources of uncertainty inherent in the diagnostic process. Starting with the first comprehensive description of CF in 1938, the dissertation traces the development and use of numerous diagnostic approaches throughout the twentieth and twenty first centuries to explore the complexity of diagnosis. As the definition of CF has shifted from a specific disease of the pancreas to a systemic disease affecting multiple organ systems, diagnostic and screening tests associated with CF have targeted not only the respiratory and gastrointestinal systems, but also sweat composition, genetics, skin changes, and lung microbiology. By foregrounding patient voices in the context of diagnostic test development and use, the dissertation also reveals the profound toll that diagnostic uncertainty can take on patients and their families. Examining efforts to diagnose a single disease over more than eighty years, the dissertation highlights the shortcomings of a reductionist biomedical model that relies on diagnostic technologies to identify specific disease entities. Key sources of uncertainty identified in the dissertation include technical challenges associated with performing or interpreting a diagnostic test, changing definitions of disease, and biases associated with race, gender, and age. Further, as the CF case illustrates, diagnostic uncertainty has persisted despite – and because of – new technologies. Each technology, introduced in the hope that it would reduce uncertainty, instead introduces novel forms of uncertainty. Since many of these diagnostic technologies (or their analogs) have been used throughout medicine, this dissertation is broadly applicable beyond CF, and demonstrates the significant harms associated with such a heavy reliance on test results and disease specificity over the patient narrative.