KEYSTONE, COLO. — A major and welcome recent development in interstitial lung disease is the greatly improved ability to prognosticate long-term outcomes in affected patients, Dr. Stephen K. Frankel said at a meeting sponsored by the National Jewish Medical and Research Center.
“Patients will come in to you and ask, 'Doc, how long do I have to live?' The last 2–3 years have taught us how to follow-up patients longitudinally and predict who'll do well and poorly—who has 2–3 years to live and who has potentially 15 years ahead of them,” explained Dr. Frankel, assistant director of the interstitial lung disease program at the center, located in Denver.
What works best, physicians have learned, is an approach that incorporates a handful of variables, including high-resolution CT findings, exercise capacity, serial measurements of forced vital capacity, and lung biopsy results.
“All of these are basically complementary and additive. So we tend to follow all of these together to determine long-term outcomes and prognoses,” he continued. These variables include:
▸ Forced vital capacity. This is the most reproducible physiologic variable. It's not the baseline number that's key to predicting long-term course, it's the change in FVC over the first 6 or 12 months of follow-up, he explained.
A study conducted by Dr. Frankel's colleagues at National Jewish on 81 patients with idiopathic pulmonary fibrosis (IPF) showed that those with a stable FVC over the first 6 months had a 5-year survival of 45%. IPF is the most common form of idiopathic interstitial lung disease.
In contrast, patients with a 10% or greater decline in FVC percentage predicted had a 5-year survival of only about 20%, while those with a 10% or more improvement in FVC percentage predicted had a 5-year survival of 70% (Am. J. Respir. Crit. Care Med. 2003;168:538–42).
This observation was confirmed in a recent double-blind placebo-controlled clinical trial of interferon g-1b in 330 IPF patients, in which a 10% or greater decline in FVC percentage predicted was associated with a 2.4-fold increased mortality risk (Chest 2005;127:171–7).
▸ High-resolution CT. Patients with CT changes that suggest fibrosis and scarring—namely honeycombing and reticulation—have worse outcomes than those with the ground-glass attenuation that indicates inflammation, he said. National Jewish investigators have developed a CT fibrosis scoring system in which a high score independently conferred a 2.7-fold increased mortality risk in a study of 315 IPF patients (Am. J. Respir. Crit. Care Med. 2005;172:488–93).
▸ Six-minute walk test. A modified version of this functional capacity test proved predictive of survival 2 years later. The significant predictors were walk distance and velocity, end-exercise saturation, and change in saturation with exercise (Eur. Respir. J. 2005;25:96–103).
▸ Disease exacerbations. Patients with mild to moderate IPF who underwent hospitalization for respiratory disorders had a more rapid disease progression and higher IPF-related mortality, Dr. Frankel said. Frequent hospitalizations may be a red flag supporting early referral for a lung transplant (Ann. Intern. Med. 2005;142:963–7).
▸ Histologic pattern on lung tissue biopsy. Patients with the bland-looking fibrosis that is characteristic of usual interstitial pneumonia have a markedly worse prognosis than patients who have nonspecific interstitial pneumonia and other inflammatory processes. Indeed, individuals with the histologic diagnosis of usual interstitial pneumonia were at 25.5 times greater mortality risk than those with nonspecific interstitial pneumonia in a prospective study of 39 patients treated with high-dose prednisone (Eur. Respir. J. 2002;19:275–83).
In patients unable to undergo lung biopsy, high-resolution CT serves as a reasonable proxy, Dr. Frankel said.