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Chest

Volume 138, Issue 3, September 2010, Pages 693-703
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Special Features
Workshop on Idiopathic Pulmonary Fibrosis in Older Adults

https://doi.org/10.1378/chest.09-3006Get rights and content

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary research, but these efforts have great potential to improve care for patients with IPF.

Section snippets

Diagnosis

IPF diagnosis relies on CT scanning of the chest or surgical lung biopsy. Yet patients often expect dyspnea to be a characteristic of normal aging; they thus limit their activity to accommodate IPF symptoms and do not consult with their physicians. For patients who do consult with them, physicians are often reluctant to perform diagnostic tests, particularly surgical lung biopsies, because of the patients' advanced age and because no standard treatment has clear benefit. Moreover, the diagnosis

Animal Models for IPF Research

Much of what is known about IPF pathogenesis comes from studies using animal models, such as mice treated with bleomycin or fluorescein isothiocyanate,20 mice overexpressing TGF-β,21 and viral infections to model potential exacerbating factors. Those models mimic acute injury and some of the histologic features of IPF (eg, collagen accumulation, architectural tissue distortion, epithelial cell hyperplasia, and isolated fibroblastic foci).22 However, none of these models mimic the entire

Cellular and Molecular Factors in IPF

Some understanding of the mechanisms underlying IPF, particularly with respect to alveolar cells, has come from studies of familial pulmonary fibrosis. Mutations in genes encoding proteins involved in the synthesis and metabolism of surfactant have been associated with chronic lung disease, and in adults, mutations in surfactant protein C (SP-C) have been associated with pulmonary fibrosis with a UIP pattern.26 In vitro, transfection of mutant SP-C results in an abundance of insoluble protein

Environmental Factors and IPF

Smoking is a major risk factor for the development of IPF. Most patients are current or former smokers at the time of IPF diagnosis,8, 9 and in families affected by the familial form of pulmonary fibrosis, ever smoking is the largest risk factor associated with eventual development of the disease.51 Smoking status affects FVC, gas exchange, and blood gases, and although its role in the natural history of IPF is not clear, smoking likely exerts synergistic effects with other factors. Exposure to

IPF and Comorbidities

Functional status is probably the most important predictor of health outcomes in older patients, and it becomes more predictive than specific diagnoses or laboratory measures as people age.64 Among patients with IPF waiting for lung transplants, performance on the 6-min walk test is more predictive of survival than lung function.65 Further, functional disability, depression, and cognitive function all predict mortality risk in older people.64, 66 Disease-associated functional decline arises

Treatment

Treatment benefit is often measured in terms of average change in a cohort of patients. This approach assumes a fairly homogeneous population. With IPF, however, there is likely a heterogeneous distribution of treatment benefit, with some patients deriving benefit from any given therapy and others deriving no benefit or even harm.92 The 2000 American Thoracic Society/European Respiratory Society consensus statement on the management of IPF pointed out that there was little evidence of

Recommended Research Priorities

Specific research questions and potential research cohorts appear in Table 4. Increasing knowledge about the natural history of IPF is chief among research priorities, as this will begin to allow identification, at the time of diagnosis, of individuals at highest risk for progression. In addition, the present diagnostic criteria for IPF are descriptive, might misclassify phenotypically similar but etiologically distinct conditions, and might miss early disease. A precise biologically based

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    • Cited by (0)

    Funding/Support: This workshop was supported by a grant from the John A. Hartford Foundation to the Association of Specialty Professors [Grant 2006-0239].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

    *

    A complete list of workshop participants is located in the e-Appendix 1.

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    Copyright © 2010 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.