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* From the University of Michigan (Drs. Flaherty, Toews, Flint, Strawderman, Lynch, Martinez, and Mr. Jain), Ann Arbor, MI; the Mayo Clinic (Dr. Colby), Scottsdale, AZ; and the Armed Forces Institute of Pathology (Dr. Travis), Washington, DC.
Correspondence to: Fernando J. Martinez, MD, FCCP, 1500 E Medical Center Dr, 3916 Taubman Center, Ann Arbor, MI 48109-0360; e-mail: fmartine{at}umich.edu
Usual interstitial pneumonia (UIP) is a progressive disorder characterized by a poor response to conventional immunosuppressive agents and significant mortality. The histologic hallmark of UIP is fibrosis, typically patchy and subpleural and paraseptal in distribution. Fibroblastic foci (FF) are interposed between areas of dense fibrosis and relatively normal-appearing lung. FF are thought to represent recent sites of injury where active collagen synthesis/fibrosis is occurring.1 We hypothesized that patients with increased FF at the time of open-lung biopsy would have decreased survival.
Three experienced pathologists (T.V.C., W.D.T., A.F.) participated in a
review of open-lung biopsy specimens from patients enrolled in our
specialized center of research study of pulmonary fibrosis. Patients
with a consensus diagnosis of UIP (n = 85), excluding those
associated with a collagen vascular illness to ensure a population of
idiopathic pulmonary fibrosis, were subsequently examined (T.V.C. and
W.D.T.), and each lobe was given a score of 0 to 3 (absent, 0; mild, 1;
moderate, 2; marked, 3) for FF. The interobserver agreement for FF was
excellent (weighted 
, 0.74; 95% confidence interval [CI], 0.63 to
0.84). The results of the two observers were then averaged. The mean
lobar FF score was 1.78 ± 0.7, and the mean maximum (highest score
in a lobe) FF score was 2.11 ± 0.7. Sixty-three patients underwent
biopsies of multiple lobes. As expected (and by definition of UIP), all
patients had FF identified in at least one lobe, although there was
variability in FF scores between lobes; this was not statistically
significant (analysis of variance, p = 0.47). In 19 patients, the FF
score was congruent, while in 44 patients, the score was discordant in
the lobes undergoing biopsy.
A Cox proportional-hazards model was used to assess the effect of FF score (mean of all lobes or maximal lobar score) for each patient on survival. An increased score for maximal FF was not associated with a worse prognosis, with a relative risk (RR) of 1.04 (p = 0.86; 95% CI, 0.68 to 1.58). A similar result was noted when the mean of lobar FF scores was examined (RR, 1.06; p = 0.79; 95% CI, 0.70 to 1.59). This analysis persisted when adjusting for patient age, gender, and smoking history. Interestingly, female sex (RR, 0.42; 95% CI, 0.18 to 0.98) and smoking history (RR, 0.43; 95% CI, 0.20 to 0.93) were associated with improved survival.
We conclude that quantification of FF in a well-characterized cohort of patients with UIP/idiopathic pulmonary fibrosis does not aid in predicting survival. It is possible, however, that FF may provide prognostic information when patients with varying types of pulmonary fibrosis (UIP and nonspecific interstitial pneumonia) are evaluated together, as recently demonstrated by Travis et al.2 In addition, multiple biopsy specimens should be obtained due to the heterogeneous distribution of FF.
Footnotes
Abbreviations: CI = confidence interval; FF = fibroblastic foci; RR = relative risk; UIP = usual interstitial pneumonia
References
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