The histopathology of fatal untreated human respiratory syncytial virus infection

Abstract

The pathology of respiratory syncytial virus (RSV) infection was evaluated 1 day after an outpatient diagnosis of RSV in a child who died in a motor vehicle accident. We then identified 11 children with bronchiolitis from the Vanderbilt University autopsy log between 1925 and 1959 who met criteria for possible RSV infection in the preintensivist era. Their tissue was re-embedded and evaluated by routine hematoxylin and eosin and PAS staining and immunostaining with RSV-specific antibodies. Tissue from three cases was immunostain-positive for RSV antigen and was examined in detail. Small bronchiole epithelium was circumferentially infected, but basal cells were spared. Both type 1 and 2 alveolar pneumocytes were also infected. Although, not possible for archival cases, tissue from the index case was evaluated by immunostaining with antibodies to define the cellular components of the inflammatory response. Inflammatory infiltrates were centered on bronchial and pulmonary arterioles and consisted of primarily CD69 þ monocytes, CD3 þ double-negative T cells, CD8 þ T cells, and neutrophils. The neutrophil distribution was predominantly between arterioles and airways, while the mononuclear cell distribution was in both airways and lung parenchyma. Most inflammatory cells were concentrated submuscular to the airway, but many cells traversed the smooth muscle into the airway epithelium and lumen. Airway obstruction was a prominent feature in all cases attributed to epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema, and compounded by compression from hyperplastic lymphoid follicles. These findings inform our understanding of RSV pathogenesis and may facilitate the development of new approaches for prevention and treatment.

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

“…A number of proinflammatory cytokines and chemokines, including CXCL8, CXCL10, and CCL5, correlate positively with disease severity (5,6). Gross and microscopic pathology from fatal cases of RSV infection are characterized by edema; small airway necrosis and sloughing; small airway plugs consisting of mucus, neutrophils, and sloughed epithelial cells; peribronchiolar and perivascular cuffing; interstitial infiltration and alveolar filling; and occasional giant cells (7)(8)(9)(10)(11). As a consequence of bronchiolitis, excess mucus production also is characteristic of RSV disease (12,13).…”

Challenges and Opportunities for Respiratory Syncytial Virus Vaccines

“…The pathologic manifestations of bronchiolitis in infants include influx of monocytes, CD3+ double-negative T-cells, CD8+ T-cells, and neutrophils into the airway smooth muscle, epithelium, and lumen. (Johnson et al, 2007) The airway obstruction in RSV-induced bronchiolitis in infants is caused by luminal epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema, in addition to extrinsic airway compression by hyperplastic lymphoid follicles. (Johnson et al, 2007) Several investigative teams have attempted to determine the immune response profile associated with severe RSV bronchiolitis in order to understand the pathogenic mechanisms leading to morbidity associated with airway obstruction during infection.…”

“…(Johnson et al, 2007) The airway obstruction in RSV-induced bronchiolitis in infants is caused by luminal epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema, in addition to extrinsic airway compression by hyperplastic lymphoid follicles. (Johnson et al, 2007) Several investigative teams have attempted to determine the immune response profile associated with severe RSV bronchiolitis in order to understand the pathogenic mechanisms leading to morbidity associated with airway obstruction during infection. Bronchoalveolar lavage (BAL) is a technique to sample the alveolar lining fluid and cells in the airway, while nasal lavage can be performed to measure the mediators and cells in the nose as a representation of the upper airway.…”

Comparing the Efficacy of 7%, 3% and 0.9% Saline in Moderate to Severe Bronchiolitis in Infants

“…On the other hand epithelial regeneration with nonciliated cells happens thus decreasing mucociliary clearance. Lymphocytic infiltration may result in submucosal edema (7). Johnson et al (7) demonstrated that, airway obstruction in bronchiolitis was because of epithelial and inflammatory cell debris.…”

“…Lymphocytic infiltration may result in submucosal edema (7). Johnson et al (7) demonstrated that, airway obstruction in bronchiolitis was because of epithelial and inflammatory cell debris. And they did not observe bronchial smooth muscle constriction.…”