Idiopathic Pulmonary Fibrosis

Jeffrey Swigris, Kevin K Brown

• Publisher: Elsevier
• Year: 2018
• ISBN:
  9780323544320
• Topic: Medizin
• Subtopic: Lungenheilkunde & Thoraxmedizin

Designed with the practicing clinician in mind, Idiopathic Pulmonary Fibrosis provides a succinct, easy-to-digest overview of this challenging condition in which the cause of thickening lung tissue is unknown. This concise resource by Drs. Kevin K. Brown and Jeff Swigris provides essential information for the physician who sees pulmonary fibrosis patients, including epidemiology, genetics and biomarkers, pathology, diagnosis, disease monitoring, and therapeutics intended to improve the patient's lifespan and quality of life.

Chapter 1

Introduction

Jeffrey Swigris, DO, MS, and Kevin K. Brown, MD

The medical community is now firmly seated in a new era of intensified awareness of fibrosing interstitial lung disease (fILD). The ubiquitous use of computed tomography (CT) of the chest to screen for lung cancer, to measure coronary artery calcification, or to rule out acute pulmonary thromboembolic disease has identified a growing number of people with lung abnormalities ranging from so-called interstitial lung abnormalities to clinically significant fILDs, like the one that affects more people than any other, idiopathic pulmonary fibrosis (IPF). The era has ushered in an improved understanding of the pathophysiologic underpinnings of IPF; the discovery of genetic factors that predispose to the development of IPF; the completion of several, large-scale, multinational, meticulously performed treatment trials; and the approval, by regulatory agencies around the world, of drugs to treat IPF.

Given the increased awareness of the condition and the enthusiasm generated by these accomplishments, we believe now is a good time to create a book that summarizes the field's knowledge of IPF. This volume includes a collection of chapters that span a broad range of topics on IPF, from pathogenesis to patient care. In each chapter, authors review and critique scientific data to yield informative yet practical synopses that we believe will be of interest to clinicians and researchers alike.

In Chapter 2, Drs. Sprunger and Olson describe the breadth of the problem of IPF from an epidemiologic perspective, reminding the reader that IPF's footprint will continue to expand as the world's aging human population increases. In Chapter 3, Drs. Mohning, Cosgrove, Downey, and Redente review what is known about the molecular and cellular mechanisms involved in generating lung fibrosis, an area of the field that has witnessed exponential growth in knowledge over the last decade. In Chapter 4, Drs. Keith and Fingerlin discuss the genetic polymorphisms or mutations that predispose people to the development of fILD. In Chapter 5, Drs. Richards, Koelsch, and Lynch describe the central role that high-resolution CT scans play in the evaluation of patients with IPF and detail the radiologic appearance of the disease. In Chapter 6, a chapter rich with exemplary figures, Drs. Achcar and Groshong highlight the characteristic pathologic appearance of usual interstitial pneumonia (UIP), the histologic pattern in IPF, and detail how to differentiate UIP from other lung injury patterns. In Chapter 7, Drs. Huie and Frankel guide the reader through a systematic approach to integrating clinical data used in making the diagnosis of IPF in a patient presenting with fILD. In Chapter 8, Drs. Solomon and Fernandez-Perez highlight how making a confident diagnosis of IPF can be a challenging endeavor that requires the exclusion of IPF look-alikes, including connective tissue disease–related ILD and chronic, fibrotic hypersensitivity pneumonitis. Next, the reader will discover a chapter by Drs. Sergew and Brown in which the authors describe the natural history of IPF and offer recommendations for carefully monitoring patients with IPF over time. In Chapter 10, Drs. Yunt, Aschner and Brown review what is known about biomarkers in IPF, an area of intense research in which investigators are striving to identify circulating molecules that can be used to more accurately and efficiently diagnose IPF and determine prognosis or response to therapeutic intervention. In Chapter 11, Drs. Ramadurai, Wakwaya, Graney, Olson, George, and Swigris cover pharmacologic and nonpharmacologic therapeutic interventions for patients with IPF.

Thank you for accessing a copy of this book. We appreciate your interest and hope you find it an enjoyable and informative reference guide to IPF.

Chapter 2

Idiopathic Pulmonary Fibrosis Epidemiology

Amy L. Olson, MD, MSPH, and David Sprunger, MD

The Epidemiology of Idiopathic Pulmonary Fibrosis

Background

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias¹ and was once considered a rare, orphan disease. Epidemiologic studies suggest that the disease burden attributable to IPF is growing, underlining the importance of ongoing research into this devastating disease.

Historically, several factors have hampered investigators in their conduct of large-scale, epidemiologic studies in IPF as follows: (1) the condition was thought to be too rare to study easily; (2) diagnostic criteria and disease assessment modalities were evolving, making the case definition a bit of a moving target; and (3) there was no specific code in the International Classification of Diseases (ICD) for IPF. The identification or, in some cases, development of large, population-level databases have helped to overcome some of these factors. For example, health insurance care claims databases have been used to determine incidence and prevalence estimates, and investigators have used death certificate databases to determine mortality rates. In addition, the generation of ICD codes that allow researchers to specifically identify IPF or other fibrotic lung diseases have been instrumental in promoting epidemiologic research using large databases. However, there are limitations associated with the use of these large datasets, including the inability to assess the fidelity of diagnostic codes.

Trends in Idiopathic Pulmonary Fibrosis Incidence and Prevalence

The incidence of disease is the number of new cases that occur during a specified period of time in a population at risk for developing the disease, whereas the prevalence of disease is a ratio of the number of affected cases present in the population at a specific time divided by the number of persons in the population at that time.²

The United States

In the early 1990s, a summary of the National Heart, Lung, and Blood Institute workshop stated that few data were available on the occurrence of IPF in the general population.³ In the wake of this summary, in 1994, Coultas and colleagues published a regional epidemiologic investigation into the incidence and prevalence of interstitial lung diseases (ILDs), including IPF, occurring in persons over the age of 18 years in the United States.⁴ Using data from 1988 through 1993, the authors established a population-based registry in Bernalillo County, New Mexico. In it, they examined primary care and pulmonary physician records, pathology reports, hospital discharge diagnoses, death certificates, and autopsy reports. The authors reported the incidence of IPF as 10.7 per 100,000 person-years in men and 7.4 per 100,000 person-years in women. The prevalence of IPF was 20.2 cases per 100,000 persons in men and 13.2 cases per 100,000 persons overall. When stratified by age and gender, both the incidence and prevalence of IPF was higher in men than in women, and each increased with increasing age.

Raghu and colleagues examined the incidence and prevalence of IPF using data from a healthcare claims processing center from 1996 through 2000.⁵ The center services a plan that covers nearly 3 million people across 20 states—mostly in the South Atlantic, South Central, and North Central regions of the United States. The authors estimated IPF incidence and prevalence for the entire United States. Using broad case-finding criteria (age > 18, at least one medical encounter for IPF [ICD-9 code 516.3], and no encounters with diagnostic codes for any other ILD after an encounter coded as IPF), they estimated an incidence of 16.3 per 100,000 persons/year and a prevalence of 42.7 per 100,000 persons, respectively. Employing narrow case-finding criteria (the broad criteria plus at least one claim with a procedure code for a surgical lung biopsy, transbronchial biopsy, or thoracic computed tomography [CT]), they estimated the incidence and prevalence at 6.8 per 100,000 persons/year and 14.0 per 100,000 persons, respectively. Like Coultas and his coinvestigators, Raghu and colleagues found that both the incidence and prevalence of IPF increased with age, and both were higher in men than in women. Based on these two landmark studies, the incidence and prevalence of IPF appeared to increase over time, but as with any study using claims data, questions remained: were cases with non-IPF ILDs counted as IPF, and were cases of IPF missed?

Using data from patients evaluated at the Mayo Clinic in Rochester from 1997 to 2005, Fernández-Pérez and colleagues completed a population-based, historical cohort study in Olmsted County, Minnesota.⁶ These authors also used both narrow and broad case-finding criteria. The narrow criteria included a usual interstitial pneumonia (UIP) pattern on surgical lung biopsy or a definite UIP pattern on thoracic high-resolution CT (HRCT), whereas broad criteria included the less-strict pattern on HRCT scan of possible UIP. Using the narrow definition, the age- and sex-adjusted incidence (for people over the age of 50) was 8.8 cases per 100,000 person-years (95...