Pichinde virus-induced respiratory failure due to obstruction of the small airways: structure and function.

Respiratory distress that leads to death is seen in patients with Lassa fever. The development of this respiratory problem was studied using a Pichinde virus model (10(4) plaque forming units, IP, survival time 20 +/- 1 days) in strain 13 guinea pigs (n = 35, 229-353 g) of this lethal human contagious infectious disease. Extravascular lung water to bloodless dry lung weight (EVLW/BDLW) ratio showed a modest yet significant increase in animals 13 and 18-21 days postinoculation (PI). In contrast, residual lung blood and lung radioactive 125I-labeled human serum albumin activity index were elevated only in the 18- to 21-day group. These data are consistent with the progressive severity of perivascular edema, lymphocytic pneumonitis, and some alveolar protein between days 13 and 18-21 PI. Lymphocytic pneumonitis appeared to be distributed near most airways and was proportional to the degree of Pichinde virus antigen staining of alveolar macrophages, large mononuclear cells within the pulmonary vascular and extravascular spaces, and alveolar-capillary membranes. These findings suggest that lymphocyte recruitment to the lung reflects the Pichinde virus-induced cell-mediated immune response. Obstructed small bronchi with some lumenal cell debris and hypertrophied epithelial cells were found associated with the areas of marked pneumonitis. The severe hypoxemia and modest anaerobic metabolism in association with marked tachypnea and normocapnia are consistent with small airway obstruction and wasted ventilation, since no change in arterial blood pressure, heart rate, hematocrit, hemoglobin, or blood volume was noted. These data suggest that Pichinde virus-induced respiratory failure was due to obstruction of the small airways with wasted ventilation in association with lymphocytic pneumonitis.