Abstract
Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.
Highlights
Idiopathic interstitial pneumonias (IIPs) are considered to be complex diseases with a strong interaction between genetic makeup and environmental factors [1,2,3]
Idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them
CMV immunoreactivity was detected in diffuse alveolar damage (DAD) histological patterns found in acute interstitial pneumonia (AIP) (2 cases), acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (1 case), and nonspecific interstitial pneumonia (NSIP) (1 case), and in 1 case with an organizing pneumonia (OP) histological pattern
Summary
Idiopathic interstitial pneumonias (IIPs) are considered to be complex diseases with a strong interaction between genetic makeup and environmental factors [1,2,3]. The major IIPs include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), acute interstitial pneumonia (AIP), and bronchiolitis obliterans organizing pneumonia (BOOP). They are characterized by abnormal repair and remodeling of lung parenchyma with prominent alveolar septal thickening by fibroblasts, chronic inflammatory cells, and extensive confluent alveolar lining cells. IIPs may have an acute or subacute presentation, or an acute exacerbation (AE) may occur in previously subclinical or unrecognized chronic IIPs [4,5]. AEs show a combination of an underlying fibrotic interstitial pneumonia and a superimposed form of acute lung injury, either diffuse alveolar damage (DAD) or organizing pneumonia (OP) [6].
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