Workshop on idiopathic pulmonary fibrosis in older adults

Abstract

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.

Figure 1.

Age-related changes in measures of pulmonary function. In general, decreases in elasticity result in increased residual volumes and decreased vital capacity as TLC does not change in the absence of substantial lung disease or comorbidity (eg, severe kyphosis). ERV = expiratory reserve volume; FRC = functional residual capacity; IRV = inspiratory reserve volume; RV = residual volume; TLC = total lung capacity; VC = vital capacity.

Figure 2.

Onset of idiopathic pulmonary fibrosis (IPF) usually occurs between the ages of 50 and 70 years, but the mean age in this population of patients with IPF was 61.4 years (n = 238, age range 27-79 years). Sixty-five percent of the subjects were ≥ 60 years of age (< 50 years, n = 36; 50-59 years, n = 48; 60-70 years, n = 108; > 70 years, n = 46). (Data from King et al).

Figure 3.

(A) Mice with accelerated aging process (SAMP8) develop more pronounced fibrosis in response to bleomycin, as shown by histology and hydroxyproline content, compared with mice that are resistant to aging (SAMR1). Fibrosis in these animals is accompanied by the presence of high numbers of mesenchymal progenitor cells in the blood fibrocytes (not shown). (hematoxylin and eosin and Masson trichrome; magnification × 10 and × 40.) (B) Bone marrow-derived mesenchymal stem cells, which are less differentiated than fibrocytes, do not differentiate into chondrocytes in aging mice as they do in senescence-resistant mice, suggesting that they might already be “destined” to become fibrocytes and thus promote fibrosis in aging individuals. (alcian blue for chondrocytes [blue cells] and oil red O staining for adipocytes [red cells]; magnification × 20 and × 100.) (Reprinted with permission from Xu et al.)

Figure 4.

Patients aged > 60 years form the largest growing segment of transplant recipients, with an increase of 648% since 1996 and 175% since 2004 (A). Although survival is lower in this group, the absolute difference at 2 years is < 10% when compared with any of the younger cohorts (B).