Clinical Pearls & Morning Reports
The diagnosis of interstitial lung disease is rarely straightforward. The most precise final diagnoses arise from multidisciplinary discussion among clinicians, radiologists, and pathologists; despite our best efforts, many cases will not have a clear diagnosis and are categorized as unclassifiable disease. Read the latest Case Records of the Massachusetts General Hospital here.
Q: What categories of disease are presently used to classify potential etiologies of interstitial lung disease?
A: A simplified division of interstitial lung disease includes three broad categories: intrinsic, including systemic disease and familial disease; extrinsic, including disease related to exposures, such as environmental substances, radiation, or drugs; and idiopathic, including idiopathic pulmonary fibrosis and other uncommon diseases that are defined by their histologic patterns.
Q: What are some of the features of idiopathic pulmonary fibrosis?
A: Idiopathic pulmonary fibrosis is a fatal disease of progressive lung fibrosis. Almost all patients with idiopathic pulmonary fibrosis are older than 50 years of age, and presentation with fibrotic interstitial lung disease at an age above 69 years is highly predictive of this diagnosis. The incidence is increased among smokers. Diagnosis begins with ruling out systemic diseases and exposures associated with lung fibrosis. High-resolution chest computed tomography (CT) is then performed to assess for the typical pattern on imaging, which is usual interstitial pneumonia.
A: Updated guidelines suggest categorizing the pattern on high-resolution CT as usual interstitial pneumonia, probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, or an alternative diagnosis. The pattern of usual interstitial pneumonia is predominantly subpleural and basal, with honeycombing; there may also be traction bronchiectasis or bronchiolectasis. Probable usual interstitial pneumonia is defined by a predominantly subpleural and basal reticular pattern with traction bronchiectasis or bronchiolectasis, without honeycombing. Either pattern may have a heterogeneous distribution and include some ground-glass opacities. When there are only subtle findings of limited reticulation in a subpleural and basal distribution or when the features and the distribution of fibrosis do not suggest a specific cause, the scan is considered to be indeterminate for usual interstitial pneumonia. The presence of profuse micronodules, marked centrilobular or other nodules, consolidations, nonhoneycomb cysts, extensive ground-glass opacities, or marked mosaic attenuation would support alternative diagnoses, as would the presence of substantial perilymphatic or peribronchovascular fibrosis.
A: Traditionally, idiopathic pulmonary fibrosis was thought to result from ongoing inflammation; however, a clinical trial of combination therapy with prednisone, azathioprine, and N-acetylcysteine did not show efficacy. In fact, this regimen resulted in an increased risk of death, which caused early termination of the trial. Until 2014, there were no effective treatments for idiopathic pulmonary fibrosis aside from lung transplantation. A major breakthrough in the management of idiopathic pulmonary fibrosis occurred when the results of two large randomized, controlled trials showed the efficacy of antifibrotic therapies — pirfenidone and nintedanib — in reducing the decline in forced vital capacity. The patients who were included in these trials had mild-to moderate disease, as determined by the degree of physiological impairment on pulmonary-function testing. On the basis of currently available evidence, the two medications are considered to be equally efficacious in slowing disease progression, with the choice of specific therapy often depending on patient preference regarding potential side effects.