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Pennsylvania Idiopathic Pulmonary Fibrosis
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American Journal of Respiratory and Critical Care Medicine

Am J Respir Crit Care Med 175:1101-1102.

Taking the "Idio" Out of Idiopathic Pulmonary Fibrosis: A call to Arms.

David M. Center, MD (2007)


The Merriam-Webster dictionary lists two uses for "idiopathic" (1). The primary definition is one we have embraced in medicine as part of the litany (e.g., hereditary, infectious, etc.) of potential causes for every ailment: "arising spontaneously or from an obscure or unknown cause." This use has been embarrassingly accurate for the pathologic findings in lung parenchyma that we call idiopathic pulmonary fibrosis (IPF) (2, 3). Of note, we don't know the causes of other pathologic patterns of pulmonary fibrosis (e.g., desquamative interstitial pneumonia [DIP] or nonspecific interstitial pneumonia [NSIP]) either. IPF has been "idiopathic" at multiple levels. We don't know the initiating factors or injuries, and we don't know why the fibrosis is progressive and dysregulated.

Am J Respir Crit Care Med 2007 Oct 1;176(7):636-643. Epub 2007 Jun 21.

Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE, Jr., Lasky JA, Loyd JE, NOth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Muller-Quernheim J, Myers JL, Nicholson AG, Selan M, Toews GB, Wells AU, Martines FJ


The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

Am J Respir Crit Care Med. 2007 Aug 1;176(3):277-84. Epub 2007 May 3

Mortality from Pulmonary Fibrosis Increased in the United States from 1992 to 2003.

Olson AL , Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK


Rationale: From the late 1970s to the early 1990s, studies found that mortality rates for pulmonary fibrosis were increasing. Recent data for mortality from pulmonary fibrosis are unavailable.

Objectives: We sought to determine mortality rates for pulmonary fibrosis in the United States from 1992 through 2003.

Methods: Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with pulmonary fibrosis and stratified the data to determine differences in mortality rates by age, sex, race/ethnicity, and geography of the decedent. We developed a multivariable model to predict future mortality rates, and we determined the underlying cause of death in patients with pulmonary fibrosis.

Measurements and Main Results : From 1992 to 2003, there were 28,176,224 deaths in the United States and 175,088 decedents with pulmonary fibrosis. The average age- and sex-adjusted mortality rate was 50.8 per 1,000,000 people. The age-adjusted mortality rate increased 28.4% in men (from 40.2 deaths per 1,000,000 in 1992 to 61.9 deaths per 1,000,000 in 2003) and 41.3% in women (from 39.0 deaths per 1,000,000 in 1992 to 55.1 deaths per 1,000,000 in 2003). While increases were significant in both men and women (p < 0.0001), the rate of increase was higher in women (p < 0.0001). The most common cause of death in patients with pulmonary fibrosis was the disease itself.

Conclusions: From 1992 to 2003, mortality rates for pulmonary fibrosis significantly increased. Further investigation is needed to determine the etiology of these trends, which are predicted to continue to increase.

Am J Respir Crit Care Med. 2006 Oct 1;174(7):810-6. Epub 2006 Jun 29.

Incidence and prevalence of idiopathic pulmonary fibrosis

Raghu G, Weyker D, Edelsberg J, Bradford WZ, Oster G


Rationale: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown etiology; its epidemiology in the United States has not been well characterized.

Objective: To estimate the annual incidence and prevalence of idiopathic pulmonary fibrosis in the United States.

Methods: Retrospective cohort design utilizing a large health care claims database spanning the period January 1996 through December 2000.

Measurements and Main Results: Persons with idiopathic pulmonary fibrosis were identified based on diagnosis and procedure codes. Using broad case-finding criteria, prevalence was estimated to range from 4.0 per 100,000 persons aged 18 to 34 yr to 227.2 per 100,000 among those 75 yr or older; annual incidence was estimated to range from 1.2 to 76.4 per 100,000. Using narrow case-finding criteria, prevalence ranged from 0.8 to 64.7 per 100,000 persons; comparable figures for incidence were 0.4 to 27.1 per 100,000 persons. Extrapolating these rates to the overall United States ' population, prevalence was estimated to be 42.7 per 100,000 (incidence, 16.3 per 100,000) using broad criteria; with narrow criteria, prevalence was estimated to be 14.0 per 100,000 (incidence, 6.8 per 100,000).

Conclusions: Our results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported.

Am J Respir Crit Care Med. 2007 Oct 1;176(7):698-705. Epub 2007 Jul 19.

Interstitial lung disease in familial pulmonary fibrosis

Rosas IO, ren P, Avila NA, Chow CK, Franks TJ, Travis WD, McCoy JP, Jr., May RM, Wu HP, Nguyen DM, Arcos-Burgos M, Macdonald SD, Gochuico BR


Rationale: Identification of early, asymptomatic interstitial lung disease (ILD) in populations at risk of developing idiopathic pulmonary fibrosis (IPF) may improve the understanding of the natural history of IPF.

Objectives: To determine clinical, radiographic, physiologic, and pathologic features of asymptomatic ILD in family members of patients with familial IPF.

Methods: One hundred sixty-four subjects from 18 kindreds affected with familial IPF were evaluated for ILD. Bronchoalveolar lavage fluid cells were analyzed using flow cytometry. Lung biopsies were performed in six subjects with asymptomatic ILD.

Measurements and Main Results: High-resolution computed tomography abnormalities suggesting ILD were identified in 31 (22%) of 143 asymptomatic subjects. Subjects with asymptomatic ILD were significantly younger than subjects with known familial IPF (P < 0.001) and significantly older than related subjects without lung disease (P < 0.001). A history of smoking was identified in 45% of subjects with asymptomatic ILD and in 67% of subjects with familial IPF; these percentages were significantly higher than that of related subjects without lung disease (23%) (P = 0.02 and P < 0.001, respectively). Percentages of activated CD4+ lymphocytes were significantly higher in bronchoalveolar lavage fluid cells from subjects with asymptomatic ILD compared with related subjects without lung disease (P < 0.001). Lung biopsies performed in subjects with asymptomatic ILD revealed diverse histologic subtypes.

Conclusions: Asymptomatic ILD in individuals at risk of developing familial IPF can be identified using high-resolution computed tomography scan of the chest, especially in those with a history of smoking. Lung biopsies from individuals in this cohort with early asymptomatic lung disease demonstrate various histologic subtypes of ILD.