Decreased tobacco-glycoprotein-induced lymphocyte proliferation in vitro in pulmonary eosinophilic granuloma.

Pulmonary eosinophilic granuloma is a disorder caused by localized collections of proliferating histiocytes in the lung. Little is known about its etiology except that the majority (58 to 97%) of patients are current or ex-smokers, making the potential etiologic role of tobacco products an important area for research. Tobacco glycoprotein (TGP) is a potent immunostimulator that has been isolated from cigarette smoke. TGP-specific lymphocyte proliferation, and cytokine production in vitro, were measured in three patients with pulmonary eosinophilic granuloma in remission and in three closely matched normal subjects with similar smoking histories. One patient with eosinophilic granuloma of bone and a matched control subject were also studied. Peripheral blood mononuclear cells were cultured with TGP, the recall antigen streptokinase (SK), and the mitogen concanavalin A (Con A). All three of the patients with pulmonary eosinophilic granuloma exhibited significant decreases in lymphocyte stimulation to TGP, despite normal responses to SK and Con A. In contrast, the response of the patient with eosinophilic granuloma of bone was higher than her matched control. The mean responses of the patients with pulmonary eosinophilic granuloma to TGP was significantly lower than the mean of nondiseased smokers or of normal nonsmokers. Twenty-four-hour culture supernatants were collected and assayed for cytokine levels (IL-1, IL-2, and IL-6). TGP-stimulated IL-2 production was significantly lower in the patients with pulmonary eosinophilic granuloma than in the normal subjects, confirming the reduced T-cell proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased immune reactivity to house dust mites in adults with chronic rhinosinusitis.

Sixty-three adults with symptomatic chronic rhinosinusitis had computerized tomographic (CT) scans of the paranasal sinuses, which were used to quantify disease severity. These patients were divided into three closely age- and sex-matched groups: a CT scan-negative group (chronic rhinitis only), a mild sinusitis group and a severe sinusitis group. Serum dust mite-specific IgG levels were found to be significantly elevated in the sinusitis patients compared with a matched group of asymptomatic normal individuals. Levels were highest in the more severe sinusitis group, in which the mean titre was 559 U/ml and the incidence of titres greater than 400 U/ml was 48%, as compared with a mean titre of 139 U/ml and only a 10% incidence of titres greater than 400 U/ml in the normal subjects (P < 0.005 and < 0.01). In contrast, although the frequency of immediate hypersensitivity to dust mite, as assessed by intradermal skin tests, tended to be higher in patients with sinusitis, it was not significantly different from normal individuals. The association between mite IgG and disease was most striking in the patient sub-group with negative mite skin tests. In this group, mite IgG levels were significantly higher than normal, even in those patients with only chronic rhinitis. These findings demonstrate that increased serum levels of IgG against dust mites are strongly associated with chronic rhinosinusitis, especially in the sub-group of patients who are not allergic to mites.

Pneumocystis carinii pneumonia presenting as asthma: increased bronchial hyperresponsiveness in Pneumocystis carinii pneumonia.

Two male patients presented with clinical and laboratory findings consistent with typical bronchial asthma and subsequently developed Pneumocystis carinii pneumonia (PCP). Only on subsequent questioning did both admit to homosexuality and behavior associated with a high risk of HIV-infection. In order to determine how frequently reversible airway obstruction is seen in patients with PCP, we measured peak expiratory flow rates (PEFR) before and after bronchodilator administration in 37 of these patients. Initial PEFR measurements revealed a significant decrease in PEFR (< 80% predicted) in 84%, with 54% of these exhibiting a significant bronchodilator response (> or = 15% increase). For comparison, peak flow measurements were made in a control group of 31 HIV-infected patients without acute PCP, divided between those with asymptomatic HIV-infection, AIDS-related complex (ARC), and AIDS, (including patients with previous PCP). Only 23% of these individuals had low PEFR, and only 3% exhibited bronchodilator responses. In order to confirm the existence of bronchial hyperreactivity in patients with PCP, another 16 patients with PCP were tested by methacholine bronchial challenge and 50% were found to have positive responses. These findings suggest that both reversible airway obstruction and airway hyperreactivity are found in association with acute PCP and that as a result some patients with PCP may present with symptoms of asthma. It is important for physicians to have a high degree of suspicion to avoid missing a diagnosis of PCP in a patient presenting with apparent asthma.

Natural immunity to dust mites in patients with chronic rhinosinusitis.

Chronic rhinosinusitis is an extremely common clinical problem of which the etiology is poorly understood. To understand the role of common environmental antigens in this disease, natural immunity to antigens derived from the house dust mite was evaluated in 22 adults with chronic rhinosinusitis and compared to a carefully matched group of patients with chronic asthma or to a group of normal individuals. Allergic reactivity to dust mites was very common in patients with chronic rhinosinusitis, with 68% exhibiting a positive immediate skin test reaction and 41% exhibiting elevated levels of mite-specific serum IgE; 72% of patients with rhinosinusitis also exhibited markedly elevated levels of mite-specific serum IgG, which were present in both mite-allergic and nonallergic patients. IgG titers were much higher in the group with rhinosinusitis than in patients with asthma, whereas allergic reactivity to dust mites was significantly higher in the patients with asthma. Mite-specific immunity was low or absent in the group of normal individuals. These findings demonstrate that natural immunity to dust mites is very common in patients with chronic rhinosinusitis and suggest that immunity to mites may be involved in this syndrome. Furthermore, the data indicate that there may be significant differences in the ability of patients with rhinosinusitis or asthma to produce mite-specific antibodies of the IgG class.

Effect of inoculation of sarcoid tissue into athymic (nude) mice.

Previous reports have suggested that the inoculation of sterile homogenates of human sarcoidosis tissue produce pathological changes or death in T cell deficient mice, while other reports have challenged these results. Because of the importance of this point, the potential infectiousness of human sarcoid tissue was investigated using athymic (nude) mice. Eight tissue specimens were obtained from patients with sarcoidosis and inoculated once into a total of sixty-two nude mice. These experiments were conducted over a period of two years. The tissue specimens inoculated included biopsies of lung, lymph node and muscle. A non-tissue buffer was used as a sham control and inoculated into ten nude mice. Of the eight tissue specimens, six were found to contain non-caseating granulomas consistent with sarcoidosis. Only one of these six specimens induced significant pathological changes when injected into nude mice: two mice developed reticulum cell sarcoma and one developed membranous glomerulonephritis. Five inoculations of sarcoid tissue into a new athymic mouse colony housed in resterilized cages produced no detectable pathology. Two different tissue specimens not containing sarcoid granulomas were inoculated into two groups of nude mice. Both of these specimens induced pathological changes. One mouse developed a reticulum cell sarcoma, one developed lymphoma and one developed interstitial nephritis. A saline control inoculation produced no pathology in any mice. Mortality rates were similar in sarcoid inoculated, normal tissue inoculated and saline inoculated mice. These findings suggest that if sarcoidosis has an infectious etiology, the responsible agent is not one that easily infects athymic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Sarcoid and cytotoxic lung antibodies.

Fifteen cases of Sarcoidosis were investigated for the presence of complement dependent cytotoxicity against human lung cells grown in tissue culture. Significant levels were found in eleven cases. Absorption studies revealed that these antibodies associated with sarcoidosis could be absorbed by human lung fibroblasts but not by fibroblasts derived from human foreskin or kidney. Although we found a similar antibody frequently associated with extrinsic asthma we have only rarely found these antibodies in cases of tuberculosis, carcinoma of the lung, emphysema and intrinsic asthma.

Antilung antibodies in asthma.

Twenty-four asthmatic patients were evaluated for the presence of circulating cytotoxic lung antibodies. These patients were further classified as either extrinsic or intrinsic asthmatics on the basis of skin testing, age of onset, and atopic history. Of the 12 patients considered to have extrinsic asthma, 10 had positive titers, one borderline, and one negative for cytotoxic lung antibodies. In the group of 12 patients classified as intrinsic asthmatics, eight had negative titers, two borderline, and two positive for cytotoxic lung antibodies. Adsorption studies indicated that these antibodies were organ-specific. Twenty normal non-smoking controls were also tested, all of whom were negative. Five patients with allergic rhinitis, positive intradermal skin tests, and no history of asthma were found to be negative for cytotoxic lung antibodies.