Background
Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal interstitial lung disease characterised by worsening lung function, dyspnoea and impaired health-related quality of life.1 Estimates of the public health burden of IPF vary widely depending on the disease definition used and the population studied, but recent estimates suggest an annual incidence in the USA of between 6.8 and 17.4 cases per 100 000 people.2 The incidence of IPF increases with age,1 and may be as high as 93.7 cases per 100 000 person-years among Medicare beneficiaries aged over 65.3 IPF carries a poor prognosis, with a median survival time of 2–3 years.1
Positive phase III trial results have been announced for nintedanib4 and pirfenidone,5 and in 2014, both these therapies were approved for the treatment of IPF by the US Food and Drug Administration. As these therapies are adopted into routine clinical practice, more information is needed on practice patterns and the characteristics of patients with IPF. To date, most research on the natural history of IPF has come from single-centre cohorts or clinical trials. As clinical trials in IPF have enrolled patients with relatively mild impairment of lung function and comparatively low mortality rates,6 the generalisability of these data to the broad population of patients with IPF may be limited. Furthermore, little information is available on the experience of patients with IPF, from the development of symptoms through formal diagnosis and disease progression. Patients are often misdiagnosed and delayed in receiving a diagnosis of IPF,7 ,8 with one study reporting a median delay of 2.2 years between the onset of dyspnoea and initial evaluation at a tertiary care centre.9
Once diagnosed, the clinical course of IPF is highly variable among individual patients.10–13 Clinical events such as acute exacerbations of IPF are associated with high morbidity and mortality,14–16 but their frequency and significance have not been well characterised in multicentre studies. Changes in pulmonary function have been evaluated as prognostic markers in predictive models,17–19 but these models require further validation in broader populations of patients with IPF.
Advances in understanding of the pathogenesis of IPF have fuelled increasing interest in molecular biomarkers. Genome-wide association studies have identified several variants associated with the presence of IPF,20–22 and the risk of disease progression.21 ,23 These studies and mechanistic discoveries have formed the rationale for several relatively small, exploratory studies of potential molecular biomarkers.24 ,25 To date, however, no biomarker has been demonstrated to have clinical utility in a large population of patients with IPF. A large registry incorporating longitudinally collected clinical and outcomes data with serial biological samples would help advance our understanding of biomarkers in IPF.
IPF has been shown to have a detrimental effect on health-related quality of life, with dyspnoea and cough being the primary drivers of this impairment.26 ,27 A limited body of literature supports the use of specific patient-reported outcome measures in IPF,28–30 yet few studies have characterised the impact of disease progression on activities of daily living, functional status and overall well-being. Thus, there remains a need to explore the validity and clinical utility of patient-reported outcome measures in prospective studies in patients with IPF.
The Idiopathic Pulmonary Fibrosis–PRospective Outcomes (IPF-PRO) registry is a national IPF registry in the USA. It is funded by Boehringer Ingelheim and managed as a collaborative project by the Duke Clinical Research Institute (DCRI), Boehringer Ingelheim and clinical site investigators. The objectives of the IPF-PRO registry are as follows: (1) to describe patients’ interactions with the healthcare system, including diagnostic procedures, in the 12 months prior to formal diagnosis of IPF; (2) to describe the course of IPF, including physiological changes, interactions with the healthcare system and death; (3) to characterise patient-reported outcomes in patients with IPF using self-administered questionnaires; and (4) to obtain biological samples at multiple time points from a well-characterised patient population for future research. In this manuscript, we describe the design of the IPF-PRO registry and how the data collected will expand our understanding of the natural history of IPF, current practice patterns and the impact of IPF on patients.