James N. Allen

Acute Eosinophilic Pneumonia as a Reversible Cause of Noninfectious Respiratory Failure

Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well characterized. We describe the clinical features, results of bronchoalveolar lavage, and follow-up studies of four patients with acute eosinophilic pneumonia. The patients presented with an acute febrile illness, severe hypoxemia (partial pressure of arterial oxygen less than 60 mm Hg), diffuse pulmonary infiltrates, an increased number of eosinophils (mean +/- SEM, 42 +/- 4.8 percent) in bronchoalveolar-lavage fluid, and an absence of infection and previous atopic illness. The illness resolved rapidly after treatment with erythromycin and corticosteroids. The patients received doses of oral prednisone that were tapered over 10 days to 12 weeks, and none have relapsed since the steroids were discontinued. After a minimum follow-up period of five months, clinical evaluation, chest radiography, and pulmonary-function tests have shown no residual abnormalities attributable to the acute eosinophilic pneumonia. Follow-up bronchoalveolar lavage has demonstrated less than or equal to 1 percent eosinophils in all patients. We believe that we are describing an acute form of eosinophilic lung disease distinct from previously described syndromes. It can be diagnosed by bronchoalveolar lavage and seems to respond to treatment with corticosteroids.

Bedside tracheostomy in the intensive care unit: a prospective randomized trial comparing open surgical tracheostomy with endoscopically guided percutaneous dilational tracheotomy.

Objectives Objectives of the study were 1) to analyze the complication incidence and resource utilization of two methods of bedside tracheostomy and 2) to define selection criteria for bedside tracheostomy.

Electrocardiographic Diagnosis of Right Ventricular Infarction

The electrocardiographic findings in 11 cases of acute right ventricular infarction associated with acute left ventricular inferior wall myocardial infarction are described. The diagnosis of right ventricular infarction was proved by autopsy findings in five cases and supported by hemodynamic data in the other six. Ten of the 11 patients had typical electrocardiographic changes of acute inferior myocardial infarction and one had that of inferior wall injury. Transient S-T segment elevation was present in one (lead V1) or more of the right precordial leads in eight cases. In the absence of other explanations for the S-T segment elevation, acute right ventricular infarction was most likely the cause. Therefore, when acute inferior myocardial infarction is accompanied by S-T segment elevation in the right precordial leads, the coexistence of right ventricular infarction should be suspected. The sensitivity and specificity of this electrocardiographic sign are yet to be determined.

Drug-induced eosinophilic lung disease

For most patients who have suspected drug-induced eosinophilic lung disease, the history provides a presumptive diagnosis that can be confirmed by pulmonary findings and eosinophilia after cessation of the drug. As new drugs are developed and released for clinical use, many will result in eosinophilic lung disease in susceptible patients. Therefore, development of pulmonary abnormalities in conjunction with blood or lung eosinophilia after prescription ofa newly released medication should raise the possibility of drug-induced lung disease, even if that medication has not yet been reported to cause eosinophilic lung disease. In all patients, the diagnosis requires exclusion of other causes of eosinophilic lung disease by history, and, if necessary, laboratory testing or lung biopsy.

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis

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.

Measurement of Outcomes in Adults Receiving Pharmaceutical Care in a Comprehensive Asthma Outpatient Clinic

We hypothesized that a pharmacist‐provided comprehensive education program in conjunction with care provided by a pulmonologist would lead to improved economic, clinical, and humanistic outcomes in adults with asthma, compared with similar patients receiving care from a pulmonologist alone. The experimental group reported receiving more information about asthma self‐management (p=0.001), were more likely to monitor peak flow readings (p=0.004), and had increased satisfaction with care, and perceived higher quality of care. Both groups had less lost productivity, fewer emergency department visits, fewer hospitalizations, and fewer physician visits, as well as improvement in symptoms scores within 45 days. Both groups improved in all functional status domains except the mental component score of the SF‐12. Our results show a positive impact on outcomes in adults with asthma who received pharmaceutical care.

Sandwich ELISA formats designed to detect 17 kDa IL-1β significantly underestimate 35 kDa IL-1β☆☆☆

Abstract The IL-1β precursor (proIL-1β) represents a significant component of total IL-1β production in certain cell types such as keratinocytes, fibroblasts and alveolar macrophages. It has been presumed that immunodetection systems for the mature 17 kDa IL-1β can be used interchangeably for the 35 kDa intracellular proIL-1β. However, during attempts to purify alveolar macrophage proIL-1β, we found that conventional enzyme-linked immunoassays (ELISAs) (using antibodies directed against the 17 kDa mature IL-1β) underestimated the amounts of 35 kDa proIL-1β by at least ten-fold compared to detection by Western blot techniques. This difference was due to the fact that ELISAs, with an antigen capture format (i.e., that use more than one epitope), can more readily see these distinct epitopes on mature or partially processed IL-1β than on the proIL-1β molecule. This problem does not occur with the Western blot technique, either because only one antibody is needed and hence there is no stearic blockade of a second epitope or because it denatures 35 kDa proIL-1β during the immobilization step, presumably better exposing epitopes as expressed on mature 17 kDa IL-1β. The problem with the ELISA can be partially corrected by proteolytic removal of the aminoterminus of 35 kDa proIL-1β with neutrophil elastase. More accurate determinations of proIL-1β by ELISA can be made by using 35 kDa proIL-1β as the reference standard (when the 35 kDa proIL-1β is free of lower molecular weight IL-1β). These data suggest that there are conformational differences between the carboxyterminus of 35 kDa proIL-1β and mature 17 kDa IL-1β which may affect immunodetection when using antibodies directed against mature 17 kDa IL-1β.

Detection of IL-5 and IL-1 receptor antagonist in bronchoalveolar lavage fluid in acute eosinophilic pneumonia

BACKGROUND Acute eosinophilic pneumonia is an idiopathic cause of respiratory failure, characterized by very high numbers of alveolar eosinophils without significant blood eosinophilia. OBJECTIVE The purpose of this study was to determine which cytokines are associated with acute eosinophilic pneumonia. METHODS Soluble IL-1 type II receptor and the cytokines IL-1 beta, IL-1ra, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha were measured in serum and in bronchoalveolar lavage fluid from two patients with acute eosinophilic pneumonia during both acute and convalescent phases. RESULTS Compared with patients with adult respiratory distress syndrome, the patients with acute eosinophilic pneumonia had high bronchoalveolar lavage fluid levels of IL-5, IL-1ra, and soluble type II IL-1 receptor but not IL-1 beta, tumor necrosis factor-alpha, IL-3, or granulocyte-macrophage colony-stimulating factor. Bronchoalveolar lavage fluid levels of IL-5 and IL-1ra fell after resolution of symptoms. In the serum of patients with acute eosinophilic pneumonia, IL-5 was not detectable, and IL-1ra was initially high but fell after corticosteroid treatment. CONCLUSION Acute eosinophilic pneumonia is characterized by locally high levels of IL-5, IL-1ra, and soluble type II IL-1 receptor in the alveolar space.

The Role of Anti–Endothelial Cell Antibody–Mediated Microvascular Injury in the Evolution of Pulmonary Fibrosis in the Setting of Collagen Vascular Disease

We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immuno-fluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjögren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half. All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western Blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins. Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response.

Transfusion-Associated Graft-vs-Host Disease A Fatal Case Caused by Blood From an Unrelated HLA Homozygous Donor

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare complication of transfusion. We report fatal TA-GVHD in a 63-year-old coronary artery bypass patient of European descent after an RBC transfusion from an unrelated donor. The patient had mild lymphocytopenia and received 2 80-mg doses of methylprednisolone and 7 units of RBCs. On day 14 after the transfusion, he had fever, elevated liver enzyme levels, and a macular rash. Pancytopenia and bone marrow aplasia developed. On day 26, he had a massive gastrointestinal hemorrhage and died. At autopsy, histopathologic findings of the skin, liver, bone marrow, and gastrointestinal tract were consistent with TA-GVHD. One donor of the transfused RBCs (3 days old at transfusion) had a 1-way HLA match with the patient. A method using multiplex polymerase chain reaction is presented. This patient with TA-GVHD and mild immune suppression suggests that blood component irradiation guidelines may need to be reevaluated.