Department of Radiology, University of Michigan Medical Center, Ann Arbor,
USA.
Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity
and mortality despite aggressive therapy. Thirty-eight patients with
biopsy-proven IPF were studied to identify pretreatment features that could
be used to predict short-term improvement in pulmonary function and improved
longer term survival. In all patients, a pretreatment clinical (dyspnea),
radiographic (chest radiograph), and physiologic (pulmonary function
including exercise saturation) score was generated (CRP). A high-resolution
CT scan (HRCT) was independently scored by four radiologists for ground
glass (CT-alv) and linear opacity (CT-fib) on a scale of 0-4. Open lung
biopsy samples were scored for cellular infiltration, interstitial fibrosis,
desquamation, and granulation by an experienced pulmonary pathologist. All
patients were treated with 3 mo of high-dose steroids and the CRP scoring
repeated. Patients were divided into three groups: responders with a greater
than 10-point drop in CRP (n = 10); stable with +/- 10 point change in CRP (n
= 14); and nonresponders with > 10 point rise in CRP or death (n = 14).
Those responding to steroids were treated for 18 mo in a tapering fashion.
In all others, steroids were tapered quickly and oral cyclophosphamide
prescribed. Responders (10 of 38) had a lower age (45.1+/-4.3 yr) than
nonresponders (61.4+/-3.5 yr) or those remaining stable (53.1+/-3.3 yr) (p =
0.01). Pretreatment CRP was higher in responders (58.8+/-5.6) than
nonresponders (40.5+/-4.7) or stable individuals (37.6+/-4.7) (p = 0.01).
Cellular infiltration score of the open lung biopsies was higher in
responders (7.6+/-0.6) than stable individuals (5.7+/-0.5) (p = 0.04). The
CT-alv scores were higher and CT-fib scores were lower in responders than
nonresponders. Receiver operating curve (ROC) analysis was employed to
identify pretreatment features of longer term survival (follow-up of
29.1+/-2.3 mo). Only CT-fib (p = 0.009) and pathology fibrosis score (p =
0.03) were able to predict mortality. A pretreatment CT-fib score > or =
2.0 demonstrated 80% sensitivity and 85% specificity in predicting survival.
Those patients who did not respond to initial steroid therapy demonstrated a
worse long-term survival and greater likelihood of decreased pulmonary
function. We demonstrate that pretherapy pulmonary function, pathologic and
radiographic parameters are different in individuals who respond to initial
prednisone therapy. Only HRCT imaging and pathologic fibrosis were able to
reliably predict long-term survival in patients with biopsy-proven IPF.