Idiopathic acute eosinophilic pneumonia (AEP) is an acute febrile illness that may be mistaken for an infectious pneumonia. Patients are often young and otherwise healthy. Clues to considering this disorder in a differential diagnosis include the acuity and severity of the clinical presentation and an initial chest X-ray with diffuse infiltrates, often interstitial, and the presence of Kerley B lines and/or evidence of pleural fluid. The diagnosis can be made through examination of bronchoalveolar lavage fluid in most cases, with careful exclusion of other similar eosinophilic lung disease. Although it can lead to life-threatening respiratory failure, AEP is easily treatable with corticosteroids. This disease has not been reported to recur in any patients to this point.

Septal capillary injury accompanied by direct and indirect immunofluorescent evidence of humoral immunity is a frequent finding on transbronchial biopsies. The findings suggest that humoral immunity to endothelial-based alloantigen is a common occurrence in lung grafts and may be a critical factor in chronic graft dysfunction.

We have recently recognized humoral rejection (HR) in lung allograft recipients and its association with acute and chronic graft dysfunction. We have shown that C4d, a stable marker of classic complement activation, is deposited in lung allografts, correlating with clinical rejection and parenchymal injury. The antigenic target may be endothelium in the setting of recurrent acute rejection while varying components of the bronchial wall may be important in chronic graft dysfunction. We sought to establish whether there is a role for antibodies with histocompatibility antigen specificity in the lung humoral allograft phenomenon. Flow cytometric and ELISA assays to assess donor-specific antigens were conducted on sera from 25 lung transplant recipients who had experienced one or more episodes of clinical rejection; in addition, the serum samples were tested for evidence of antiendothelial cell antibody activity. Morphologically, each case had biopsies showing septal capillary injury with significant deposits of immunoreactants with microvascular localization and positive indirect immunofluorescent antiendothelial cell antibody assay. Panel-reactive antibody testing showed absence of MHC Class I/II alloantibodies; ELISA based crossmatch detecting donor-specific MHC Class I/II specific antibodies was negative. HR can occur in the absence of antibodies with HLA specificity; antigenic targets may be of endothelial cell origin.

Acute eosinophilic pneumonia should be considered as a possible diagnosis when a previously healthy person presents with acute respiratory failure of unknown origin.

Interstitial lung disease compatible with idiopathic pulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome. Significantly elevated factor VIII levels were seen in 17 of 18 patients tested. Antiphospholipids were present in all 18 patients tested, comprising antibodies of phosphatidylethanolamine, beta-2 glycoprotein, phosphatidylcholine, and/or phosphatidylserine. Anti-Ro and/or anti-ribonucleoprotein (RNP) antibodies were seen in 4 patients. Serologic evidence of infection with cytomegalovirus (CMV) was found in 9 patients and parvovirus B19 (B19) in 9 patients; 1 patient was not tested. Molecular studies revealed B19 DNA in 6 of 6 B19-seropositive patients. In situ hybridization studies revealed CMV RNA in pulmonary cells in patients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, and/or endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPF. This report underscores the potential importance of microvascular injury in the evolution of IPF.

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Animal studies have shown that blockade of complement may reduce the severity of and/or prevent the development of bronchiolitis obliterans syndrome (BOS), suggesting a role for complement activation. We explored the hypothesis that humoral immunity plays a role in the evolution of BOS. Thirteen unilateral lung transplant patients with BOS defined the patient population. Fresh frozen tissue was analyzed for deposition of C1q, C4d, C5b‐9 and immunoglobulin (IgG, IgM, IgA). An indirect immunofluorescent assay was also conducted with patient serum against cytospins of the pulmonary endothelium. In each case the biopsies showed a microvascular injury syndrome involving the bronchial wall characterized by one or more of hemorrhage, fibrin deposition, and endothelial cell necrosis. Other features included bronchial epithelial and chondrocyte necrosis. The end‐stage lesion was a thinned bronchial epithelial lining mural fibrosis. Immunofluorescent analysis showed deposition of C1q, C3, C4d, C5b‐9, and immunoglobulin in the bronchial epithelium, chondrocytes, basement membrane zone of the bronchial epithelium, and bronchial wall microvasculature. The indirect antiendothelial cell antibody assay was positive in all tested. Humoral immunity may play a role in the pathogenesis of BOS; the antigenic targets include the bronchial wall microvasculature, bronchial epithelium, and chondrocytes.