Helen A. Dickie

Nitrogen dioxide-induced pulmonary disease: five new cases and a review of the leterature.

Twenty-three patients exposed to nitrogen dioxide in agriculture or industry were referred to the University of Wisconsin Medical Center. Eighteen experienced a transient upper respiratory tract syndrome; five developed pulmonary edema or bronchiolitis obliterans. This latter group responded to steroid therapy but all demonstrated evidence of persistent pulmonary dysfunction on follow-up studies. Combining our findings with those in the literature we concluded: (1) exposure to NO2 is more common than generally appreciated; (2) case fatality is high--29% for silo-fillers disease; (3) steroids are effective therapy and should be continued for at least eight weeks; (4) although the majority recover without significant sequelae, some individuals may develop persistent functional abnormalities; (5) there is no evidence that long-term exposure to low concentrations of NO2 leads to chronic airway obstruction; and, (6) NO2-induced pulmonary disease could be elminated with appropriate preventive measures.

Relationships between prednisone therapy, disease activity, and the total serum IgE level in allergic bronchopulmonary aspergillosis☆

Allergic bronchopulmonary aspergillosis (ABPA) is an unusual syndrome caused by hypersensitivity to Aspergillus spores growing in the bronchii. Previous investigators have suggested that the IgE levels and precipitating antibodies may vary according to disease activity. We have been able to closely follow 12 out of a group of 40 ABPA patients with IgE and serum precipitating antibody measurements. Our results confirm that both the total serum IgE and the precipitin response vary according to ABPA disease activity. In particular the IgE trend appears to mirror the disease activity in that a rising level may portend a flare, while a stable or declining value implies disease remission.

Antigens in moldy hay as the cause of farmer's lung.

Summary Sera from farmers lung patients and non-farmers lung control individuals were reacted with trichloroacetic acid extracts of moldy hays. All the sera from patients with acute symptoms and two-thirds of the total which included recovered farmers lung patients formed specific precipitin lines with the moldy hay extracts. No precipitin lines were obtained with sera from healthy farmers who had no history of farmers lung or with extracts of good hay. Evidence is presented to show that farmers lung is associated with the presence of specific antibodies in the patients“sera against antigens found in moldy hays and that these antigens are the cause of farmers lung.

Farmer's lung.

Excerpt We have previously described the clincal features of an acute granulomatous interstitial pneumonitis that occurred in 39 agricultural workers after exposure to moldy organic farm dusts (1)....

Pathogenicity of specific glycopeptide antigen in farmer's lung.

Summary Six patients with Farmers Lung and 10 controls were challenged with an antigen extracted from moldy hay by aerosol inhalation. Precipitin reactions in agar gel im-munodiffusion were strongly positive in 4 patients, weakly reactive in one, and not present in one. Clinical, hematologic and physiologic data are presented on the 6 patients challenged in an identical manner and on the 10 control subjects. Responses to this challenge in the patient group were qualitatively identical to the reaction each patient experienced when exposed to moldy hay in the barn or silo. These moldy hay antigens are, thus, concluded to be the etiologic agents responsible for the disease, Farmers Lung.

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.

Lymphocyte subpopulations in the peripheral blood of patients with farmer's lung.

The numbers of mononuclear cells having receptors for sheep red blood cells (T lymphocytes) or complement (B lymphocytes) in the peripheral blood of farmers lung patients were determined. In patients recovering from a clinical episode of farmers lung or exposed to moldy hay or fodder, both the percentage of T lymphocytes and the T lymphocytes per mm3 were reduced, whereas the number of B lymphocytes remained within normal limits. Farmers lung patients having no exposure to moldy hay or fodder had T and B lymphocyte numbers similar to a normal population.

Preliminary observations on a new derivative of isoniazid (Ro 2-4969).

Summary 1. Ro 2-4969, a compound of low solubility, related to isoniazid, has been administered experimentally to human subjects to determine the rate and extent of absorption from the gastrointestinal tract. 2. The compound or its derivatives appeared in the plasma and, probably because of slow absorption, detectable and clinically significant amounts remained for a longer period than when the highly soluble isoniazid was administered. 3. The drug administered in a single daily dose of 10 mg/kg/day was found to maintain drug concentrations of one μg/ml of plasma without dangerous cumulative effect. 4. No toxic reactions have been observed in 26 patients treated for 2 months or more.

SUMMARIES OF RESEARCH REPORTS

At the Research Workshop, the first paper :* was presented by Donald P. Schlueter, M.D. His coinvestigators were Drs. Jordan N. Fink and George P. Hensley, all members of The Medical College of Wisconsin. Dr. Schlueter described two paper mill workers with the clinical manifestations and laboratory findings consistent with the chronic form of hypersensitivity pneumonitis, which is also known as extrinsic allergic alveolitis. At the onset of their illness, these two patients experienced recurrent acute and sub-acute episodes of cough, dyspnea and fever, which resolved spontaneously within hours to days when they were away from the environment related to their occupation of bark stripping and chipping of logs in the production of wood pulp. Failure to recognize the early stages of this hypersensitivity pulmonary disease led to their continued exposure and the development of an advanced form of pulmonary disease, which resembled idiopathic pulmonary fibrosis. Chest x-rays showed bilateral nodular infiltrations. The abnormal pulmonary function tests demonstrated a primary restrictive type impairment with a diffusion defect. A lung biopsy also showed an interstitial granulomatous pneumonitis consistent with the diagnosis of a hypersensitivity pneumonitis. An environmental survey of their work area at the mill revealed the presence of a variety of common soil molds, which included Alternaria, Homeodendrum, Rhizopus and other varieties of contaminating molds. By means of immunodiffusion testing of the patients’ sera, precipitating antibodies were demonstrated against several of these mold antigens, with the highest titer directed against an extract of Alternaria. Both of these patients had advanced and irreversible pulmonary disease when they were first seen by these investigators. Challenge by inhalation exposure with an extract of Alternaria was attempted. Both patients developed pulmonary and systemic reactions within six hours following challenge with the alternaria antigen. It is well recognized that hypersensitivity pneumonitis may be the result of either the inhalation of a variety of fungal spores, or the dust derived from material heavily contaminated by fungi. This report is the first to describe this entity resulting from the inhalation of the common soil mold, Alternuria. Although other molds were identified within the occupational dust, the patients demonstrated lower titers of precipitating antibody to several of these molds. Unfortunately the investigators were unable to rechallenge these two paper mill