Cell Therapy Trials for Lung Diseases: Progress and Cautions

Idiopathic pulmonary fibrosis (IPF) is a catastrophic disease that in most patients is characterized by a progressive nature that confers upon it a high mortality (1). This is aggravated by lack of understanding of IPF pathogenesis, which undermines the ability to model the disease in animals and impedes development of effective therapies. Consequently, with the exception of oxygen administration and lung transplantation, the latter a limited option that improves survival in some patients, no currently effective treatment options are available (2). Despite this, the IPF community has made significant advances, and the last decade saw its transformation into a worldwide network of community- and academic-based organizations that, in conjunction with sponsorship from the pharmaceutical industry and the National Institutes of Health–sponsored IPF network, resulted in the development of rigorous clinical trials (reviewed in Reference 1). Although these were not successful in demonstrating drug efficacy in IPF treatment, they helped clarify the natural history of the disease and documented differences in disease progression, with some patients experiencing exacerbations and rapid progression, whereas others have a more protracted course (1). Genetic studies clarified the familial nature of IPF in a subset of patients and identified genetic mutations compromising telomerase function, thus linking the disease to bone marrow abnormalities (3). Clinical trials also contributed a unique repository of biological materials for identification and validation of biomarkers to follow disease progression (1). In a short period of time, these research initiatives have altered clinical practice by demonstrating that the use of azathioprine is toxic to patients with IPF, effectively eliminating the use of this drug in IPF, thus affirming the “primum non nocere” principle ({type:clinical-trial,attrs:{text:NCT00650091,term_id:NCT00650091}}NCT00650091) (4).