Paul M. Stevens

Immunoglobulin Secreting Cells in Normal Human Bronchial Lavage Fluids

Immunoglobulin secreting cells were quantitated in the bronchial lavage fluids of 12 normal volunteers and compared with immunoglobulin secreting cells in peripheral blood, by a reverse hemolytic plaque assay. The mean number of cells secreting immunoglobulin (Ig)G in bronchial lavage fluids was 489 per million lymphocytes vs. a mean of 175 IgG secreting cells per million lymphocytes in peripheral blood (P < 0.02). The mean number of IgA secreting cells in bronchial lavage fluids was 633 per million lymphocytes as compared to 100 per million lymphocytes in peripheral blood (P < 0.005). Thus, compared to peripheral blood, cells from the lavage fluids were relatively enriched for both IgG and IgA secreting cells. However, IgA secreting cells were the major class of immunoglobulin secreting cells in bronchial lavage fluids, whereas IgG secreting cells predominated in peripheral blood. The prominence of IgA secreting cells in bronchial lavage fluids was further demonstrated by a mean ratio of IgA/IgG secreting cells in bronchial lavage fluids of 1.26 compared to a ratio in peripheral blood of 0.57 (P < 0.02). Cells secreting IgM were identified in only four of seven bronchial lavage fluid samples studied but in all peripheral blood samples. IgE secreting cells were not present in normal peripheral blood but could be demonstrated in 5 of 11 lavage fluid specimens. Thus, cells actively secreting immunoglobulins can be identified in the lower bronchial-alveolar tree of normal human subjects. Cells secreting IgG, IgA, or IgM may function in local lung defenses against infection; cells secreting IgE may contribute to hypersensitivity reactions in the lung.

Regional Ventilation and Perfusion after Lung Transplantation in Patients with Emphysema

Abstract Serial 133Xe ventilation and perfusion scans were done on two patients who underwent left-lung transplantation because of severe emphysema associated with alpha1 antitrypsin deficiency. In...

The influence of PEEP on survival of patients in respiratory failure: a retrospective analysis.

Positive end expiratory pressure breathing (PEEP) is used to decrease morbidity and mortality in patients who are hypoxemic despite breathing oxygen in concentrations potentially toxic to their lungs. We reviewed the hospital course of 78 patients whose arterial oxygen tension (PaO2) was less than 70 torr despite a fraction of inspired oxygen (FiO2) of 1.0. Only 60 per cent of these patients were treated with PEEP and their clinical illnesses and severity of cardiopulmonary dysfunction were similar to those in patients not treated with PEEP. PEEP increased the length of survival from 4.2 to 9.2 days (P less than 0.05) whereas over-all survival, defined as hospital discharge, was similar at 31 per cent with and 26 per cent without PEEP. An improvement in PaO2 and decrease in shunt fraction following a trial of PEEP portends a favorable outcome, but its continued use appears to prolong life for a few days without affecting hospital mortality. Survival appears related more to the maintenance of adequate tissue oxygenation as manifested by a high mixed venous oxygen than to improved gas exchange as reflected by an increase in PaO2.

Mathematical Modeling of Pulmonary Airway Dynamics

A mathematical model has been derived that describes the pressure-flow relationship in the ventilatory system under conditions of constant lung volume. The parameters of the model include small airway resistance, large airway resistance, and lung elastic recoil. A collapsible airway segment is included to model compression of the airways during expiration.

Pathophysiology of hereditary emphysema.

Abstract Patients with decreased serum alpha1-antitrypsin were designated as severely deficient (7% to 15% of normal) or intermediately deficient (30% to 65% of normal) by quantitative radial immun...

EXTERNAL RADIOFLUX DETECTION: NONINVASIVE MEASUREMENT OF PROTEIN LEAKAGE IN ASSESSING LUNG MICROVASCULAR INJURY

Microvascular injury in the lung, by any mechanism, must invariably cause an alteration of protein permeability in perfused vessels. In animal models, detection and quantification of this change in the endothelial conductance of fluid and solute have facilitated study of the mediators involved in acute lung injury. We have described a noninvasive method for measuring the pulmonary transvascular flux of radioisotopically tagged tracer proteins that may be clinically useful.’,2 The validity of this technique, external radioflux detection, has been demonstrated by comparison of our indirect measurements with the directly measured accumulation of tracer protein in the lung lymph of sheep.’ This was done under conditions of both normal and increased vascular permeability. In normal man, our studies revealed a more rapid equilibration of In“’labeled transferrin between the vascular and interstitial spaces of the lung than was seen in the sheep. Time to half-maximum concentration of the diffusible tracer under baseline conditions was 51.9 -t 13.0 minutes (mean standard deviation, n = 9) in man and 151 _t 32 minutes [mean f SD, n = 10) in sheep. Transferrin, a &globulin, has a molecular weight of 75-80 thousand. It is normally present in human plasma at a concentration of 300 mg/dL (approximately 4.1% of total plasma protein]. In the past, we have assumed that pulmonary transvascular flux of transferrin was closely correlated with permeability to the more abundant, and oncotically important, albumin molecule. We will report measurements of pulmonary transvascular flux of albumin in normal human volunteers and in patients with chronic renal failure undergoing maintenance hemodialysis. Plasma activation by cupraphane dialysis membranes may result in lung microvascular injury,’.* and could thus serve as a readily available “model” of noncardiogenic pulmonary edema in man.

GENERAL ASSESSMENT AND SUPPORT OF THE ADULT RESPIRATORY DISTRESS SYNDROME

Adult respiratory distress syndrome (ARDS) is a catastrophic illness characterized by hypoxernia usually refractory to increasing concentrations of inspired oxygen administration. It is often accompanied by radiographic evidence of diffuse interstitial and alveolar infiltration. Athough the chest radiograph may be relatively clear in spite of severe and refractory-, hypoxemia, radiographic changes denoting increased lung water usually become obvious within 24 hours. The diagnosis is made by excluding pulmonary edema due to cardiogenic hydrostatic forces and other chronic or acute primary lung diseases, such as interstitial, bacterial, fungal, or viral pneumonias. Regardless of the specific etiology, the primary mechanism causing ARDS is a sudden increase in capillary endothelial and perhaps alveolar epithelial permeability, allowing rapid and massive accumulation of protein-rich fluid into the interstitial and alveolar space of the lung. I shall limit this discussion to only three clinical areas of importance that relate to the management of this syndrome: first, the clinical factors operative in the genesis and natural history of ARDS; second, the methods available for diagnosis and assessment of its severity; and third, the conventional approaches to therapy with recommendations as to alternate methods to improve the otherwise dismal prognosis.

Human lung allotransplantation. Report of two cases.

Abstract Although canine lung allografts have survived with function for periods up to five years, to date human lung allotransplantation has been unsuccessful with the exception of one patient now surviving more than six months after operation. This report reviews two cases of left lung transplantation for terminal pulmonary emphysema associated with serum alpha-1 globulin or antitrypsin deficiency. These patients died twenty-six and ten days after operation, respectively, and the causes of death were herpes simplex viral pneumonia in the first and bacterial pneumonia with lung abscess formation in the second. The second case was particularly disappointing in that mechanical lymphocyte depletion rather than conventional immunosuppressive therapy was employed in an attempt to prevent infectious complications. Problems encountered in the management of these patients are numerous. Many of the findings of previous experimental studies may not be applicable to the clinical situation, and much remains to be learned about human lung allotransplantation.

An unusual cause of cyanosis in a patient with a carcinoid tumor.

We report the second case of a right-to-left interatrial shunt due to a carcinoid tumor, which was successfully corrected by surgery. The patient had closure of a patent foramen ovale and tricuspid valve replacement. One and a half years after surgery, the patient had no symptoms related to heart disease.

Pulmonary coccidioidal pseudomycetoma

Coccidiomycosis is rarely associated with a pulmonary mycetoma. We report a patient with progressive cavitary coccidiomycosis, whose initial radiographic and clinical appearance simulated a mycetoma. Examination of the surgically resected lung showed necrotizing Coccidioides immitis granulomas with spherules and arthroconidialike structures, but no evidence of a mycetoma. We propose the term pulmonary coccidioidal pseudomycetoma as the best descriptor for this patients clinical, radiographic, pathologic, and microbiologic presentation.