Ozone alters the distribution of beta1 integrins in cultured primate bronchial epithelial cells.

The effects of 0.5 ppm ozone exposure for 6 h on the synthesis and distribution of beta1 integrins were examined in bronchial epithelial cells cultured at an air-cell interface. Ozone exposure damaged cilia and caused significant cell loss. Immunocytochemical localization and quantification of the beta1 subunit in the remaining attached cells using scanning laser cytometry demonstrated time-dependent changes in beta1 distribution in response to ozone. Although no changes were detected immediately after exposure, beta1 immunoreactivity increased 23 +/- 5% and 66 +/- 6% at 6 and 24 h, respectively. The increased immunostaining was localized at the apical surfaces and, to a lesser extent, at cell-cell contacts of cultured cells. Furthermore, integrin redistribution was not due to increased messenger RNA (mRNA) levels and protein synthesis because levels of beta1 mRNA and newly synthesized beta1 protein did not change after ozone exposure. However, immunoprecipitation analysis of beta1 integrins in lysates from equal numbers of cells showed that ozone-exposed cells contained 90 +/- 15% more total beta1 subunit at 24 h after exposure. In addition, our results demonstrated the presence of the alpha5beta1 integrin complex in bronchial epithelial cells and that the detergent-soluble amount of its associated beta1 subunit increased 60 +/- 10% in lysates of ozone-exposed cells. In conclusion, ozone altered cellular distribution of beta1 integrins in the remaining attached cells subsequent to cell injury and loss. The changes in beta1 distribution might be due to increased detergent extractibility of beta1 integrins rather than a real increase in the synthesis of beta1 integrins.

A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. Montelukast Asthma Study Group.

BACKGROUND: The cysteinyl leukotrienes are important mediators of bronchial asthma. The clinical effect of montelukast, a potent cysteinyl leukotriene-receptor antagonist, was investigated in a randomized, placebo-controlled, multicenter, parallel-group, dose-ranging study. METHODS: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled beta-agonists on at least two occasions) were randomly assigned to one of six treatment groups: placebo; 10, 100, or 200 mg once daily montelukast in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout period. All patients used inhaled, short-acting beta-agonists as needed. RESULTS: All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints. The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.56 to 15.04), as-needed beta-agonist use (-0.98 puffs; 95% CI: -1.53 to -0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians' and patients' global evaluations, and asthma-specific quality-of-life scores were all significant (p < or = 0.050). The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment. CONCLUSION: Montelukast caused a significant improvement in chronic asthma at an oral, once daily evening dose as low as 10 mg.

Ozone alters the expression of tenascin-C in cultured primate nasal epithelial cells.

Tenascin-C is an extracellular matrix component which is transiently expressed in association with epithelial cell detachment, proliferation, and migration. This molecule has been identified in respiratory tissue, but little is known about the cellular source of tenascin-C or the factors that regulate its production. Since air pollutants are known to disrupt epithelial integrity, we investigated the regulation of tenascin-C in response to 0.3 ppm ozone in differentiated primate nasal epithelial cells in culture at an air-medium interface. The expression of tenascin-C was upregulated in response to ozone, as determined by Northern blot analysis, Western blotting, and immunofluorescent staining. In contrast, there was no change in the mRNA levels for versican, biglycan, perlecan, or collagen type I. Reduced cellular attachment to the substrate was evident in ozone-treated cultures in association with tenascin-C deposition at the interfaces between cells and basal surfaces. The presence of tenascin-C on denuded areas of the matrix suggests that tenascin-C may have been instrumental in the loss of patches of cells. The modulation of tenascin-C synthesis and distribution may play a significant role in the response of respiratory epithelial cells to ozone exposure.

Release of RANTES from nasal and bronchial epithelial cells.

RANTES is a chemokine with eosinophil attractant and activating activities. This study was undertaken to determine whether primary cultures of human nasal and primate bronchial epithelial cells produce RANTES and the effect of various cytokines and dexamethasone on the release of this chemokine. Nasal epithelial cells from 32 patients (HNE) and bronchial epithelial cells from 17 Macaca nemestrina monkeys (PBE) were cultured in vitro for 24 to 72 h with LPS, TNF-alpha, IL-1 beta, IFN-gamma and TNF-alpha combined with IFN-gamma and/or dexamethasone at 10 to 1000 micrograms/ml. Culture supernatants were assayed for RANTES by ELISA. RANTES synthesis was measured by immunoprecipitation. HNE and PBE released modest constitutive amounts of RANTES (350 to 1000 pg/ml) which did not increase with time in culture. Release of RANTES was stimulated by all activators except LPS in a time-dependent manner, with the greatest synthesis induced by the combined addition of TNF-alpha and IFN-gamma. The combination of these activators also increased RANTES synthesis as determined by immunoprecipitation. Dexamethasone at 100 and 1000 micrograms/ml produced significant inhibition of stimulated RANTES release. These data indicate that normal nasal and bronchial epithelial cells release RANTES which is upregulated by various cytokines and inhibited by dexamethasone. The enhanced release is due to stimulation of both synthesis and secretion. Production of RANTES by epithelial cells could contribute to the inflammation that characterizes the respiratory tract in asthma and rhinitis and downregulation of RANTES by glucocorticoids may be one mechanism of the therapeutic effect of these agents.

Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma.

BACKGROUND: Cysteinyl leukotrienes mediate signs and symptoms of asthma. In a double-blind, placebo-controlled, crossover study, a new potent and specific cysteinyl leukotriene (LTD4) receptor antagonist, montelukast (MK-0476), was evaluated for tolerability and clinical efficacy in patients with chronic asthma (receiving and not receiving inhaled corticosteroids). METHODS: Twenty-nine nonsmoking patients with asthma (15 treated concomitantly with inhaled corticosteroids) with FEV1 percent predicted values between 50% to 80% received MK-0476, 200 mg, or placebo three times daily for 10 1/3 days (31 doses) in a random, crossover manner, after a 2-week, open, baseline period. Comparisons in FEV1 (mean percent change from baseline after the first and last dose), mean daily daytime asthma and nocturnal awakening scores, and mean daily beta-agonist use were made between treatment periods. RESULTS: Montelukast, compared with placebo, caused improvements in FEV1 (mean percentage point difference of the percentage change from baseline) 3 and 4 hours after dosing on day 1 (hour 3, 9.0%; 95% confidence interval [CI] 0.53, 18.72; hour four, 10.9%; 95% CI -0.25, 20.20) and day 11 (hour 3, 14.0%; 95% CI 0.76, 31.43; hour 4, 13.4%; 95% CI 1.24, 28.83). Reductions were observed in mean daily beta-agonist use (1.0 puff/day [95% CI -1.61, -0.26]), mean daytime symptom scores, and nocturnal awakenings over the 10 1/3 day treatment period. There were no important differences between the groups receiving and those not receiving inhaled corticosteroids. Montelukast was well tolerated with no serious clinical adverse events reported. CONCLUSIONS: In this study Montelukast, 200 mg, administered three times daily for 10 1/3 days, compared with placebo, was generally well tolerated and resulted in significant improvement in chronic asthma, irrespective of the presence of inhaled corticosteroids.

Prevalence of basidiomycete allergy in the USA and Europe and its relationship to allergic respiratory symptoms.

A total of 701 adults living in the USA or Western Europe who had symptoms of allergic respiratory disease were skin prick tested with extracts prepared from eight basidiomycetes species and four Fungi Imperfecti species. In these subjects, the presence of asthma, rhinitis, or both was determined by questionnaire. Overall, 178/701 (25.4%) of the participants reacted to at least one basidiomycete extract. There was no difference in the prevalence of reactivity detected in the USA and Europe (P < 0.005); however, the prevalence of reactors in individual centers from both areas varied significantly. Psilocybe cubensis was the most potent allergen source in both the USA (12.3% reacted) and Europe (16.0%). Pleurotus ostreatus was second overall (10.6%) and in the USA (10.7%), and third in Europe (10.3%). Pisolithus tinctorius and Coprinus quadrifidus produced the least potent allergens, with only 5.4% of the population reacting. There was a significant relationship (P < 0.005) between basidiospore reactivity and the presence of atopy, asthma, and asthma and rhinitis. Basidiospore reactivity was not associated with the presence of rhinitis alone (P = 0.312). These results suggest that basidiomycetes are important sources of aeroallergens in geographically disparate regions and may be particularly important in patients with asthma.

Multiple chemical sensitivity syndrome: a clinical perspective. I. Case definition, theories of pathogenesis, and research needs.

Multiple chemical sensitivity syndrome (MCS) does not appear to fit established principles of toxicology. Yet social, political, and economic forces are demanding that MCS be defined medically, even though to date scientific studies have not identified pathogenic mechanisms for the condition or any objective diagnostic criteria. Consequently, a working definition of MCS can rely only on an individual's subjective symptoms of distress and attribution to environmental exposures rather than currently measurable objective evidence of disease. Nevertheless, patients labeled with MCS are clearly distressed and many are functionally disabled. In this review, four theories of causation are explored: (1) MCS is a purely biologic/physical or psychophysiologic reaction to low-level chemical exposures. (2) MCS symptoms may be elicited by low-level environmental chemical exposures, but the sensitivity is initiated by psychologic stress. (3) MCS is a misdiagnosis and chemical exposure is not the cause. The symptoms may be due to misdiagnosed physical or psychologic illness. (4) MCS is an illness belief system manifest by culturally shaped illness behavior. Areas for further research regarding the etiologies of MCS are suggested. Recognizing that the cause of the syndrome may be multifactorial, strategies are proposed for clinical evaluation and management in Part II of this manuscript using a biopsychosocial model of illness.

Multiple chemical sensitivity syndrome: a clinical perspective. II. Evaluation, diagnostic testing, treatment, and social considerations.

Multiple chemical sensitivity syndrome (MCS) does not appear to fit established principles of toxicology. Social, political, and economic forces are demanding that MCS be defined medically, even though scientific studies have failed as yet to identify pathogenic mechanisms for the condition or any objective diagnostic criteria. Consequently, a working definition of MCS can only rely on a person's subjective symptoms of distress and attribution to environmental exposures rather than currently measurable objective evidence of disease. Nevertheless, patients labeled with MCS are clearly distressed and many are functionally disabled. Without reconciling the different theories of etiology of MCS discussed in Part I of this report, and recognizing that the cause of the syndrome may be multifactorial, strategies are proposed for clinical evaluation and management of patients with MCS using a biopsychosocial model of illness. The social implications of this illness are also discussed.

Synthesis of interleukin-1 alpha, interleukin-6, and interleukin-8 by cultured human nasal epithelial cells.

Nasal epithelium forms the initial barrier between the environment and the respiratory system and may be a potential source of proinflammatory interleukins, which contribute to the pathophysiology of allergic and nonallergic rhinitis. To explore this possibility, epithelium and cultured human nasal epithelial cells from nasal turbinates of patients undergoing surgery for treatment of upper airway obstruction were examined for the spontaneous expression of interleukin (IL)-1 alpha, IL-1 beta, IL-6, and IL-8. Human nasal epithelial cell lysates and culture supernatants were assayed by two-site ELISAs specific for IL-1 alpha, IL-1 beta, IL-6, or IL-8. Maximum concentrations of these cytokines in supernatants ranged from approximately 0.2 to 2 ng/ml for IL-1 alpha, 1.5 to 7 ng/ml for IL-6, and 100 to 3000 ng/ml for IL-8. IL-1 alpha was predominantly cell-associated, whereas most of the IL-8 and all of the IL-6 were detected in the supernatant. Little or no IL-1 beta was detected by ELISA in the supernatants or cell lysates. Whole tissue turbinates and isolated epithelium were also examined for IL-1 beta, IL-6, and IL-8 mRNA expression by Northern blot analysis. IL-6 and IL-8 mRNAs were detected, whereas IL-1 beta mRNA was not. Furthermore, IL-6 and IL-8 release from human nasal epithelial cell cultures was enhanced by addition to the cultures of lipopolysaccharide, and IL-6 release was inhibited by polymyxin B. Thus human nasal epithelium may be a major source of IL-1 alpha, IL-6, and IL-8 in allergic and nonallergic rhinitis. Production of those proinflammatory cytokines by epithelial cells of the nasal and sinus mucosa may contribute to the pathologic and clinical events that occur in these diseases.

The effects of ozone exposure on lactate dehydrogenase release from human and primate respiratory epithelial cells.

Ozone is the most persistent, wide-spread air pollutant in the United States. Over one half of the population of the US lives in cities or suburban areas which do not meet the National Ambient Air Quality Standard for ozone which is 0.12 ppm averaged over 1 h. Controlled laboratory exposures of human subjects have shown that ozone exposure produces decreased pulmonary function, hyperresponsiveness to inhaled methacholine, inspiratory pain, and airway inflammation as assessed by bronchoalveolar lavage. However, the cellular mechanisms responsible for such effects are incompletely known. The present study examined the effects of ozone exposure at 0.50 ppm for 3 h on three types of cultured respiratory epithelial cells; primary cultures of human nasal cells and primate bronchial cells, and the A549 type II pneumocyte-derived cell line. Cells were grown to confluent monolayers in plastic 6-well plates and then exposed to ozone or filtered air on a tilting platform over a heated water bath. Lactose dehydrogenase release was significantly increased following ozone exposure of all cell types; a 75% increase from human nasal cells (P = 0.0002), a 79% increase from primate bronchial cells (P = 0.003), and a 69% increase from A549 cells (P = 0.02). These data suggest that even brief ozone exposure causes membrane injury to cultured human respiratory epithelial cells.

Cytokines and eosinophil-derived cationic proteins upregulate intercellular adhesion molecule-1 on human nasal epithelial cells.

BACKGROUND: Allergic and nonallergic rhinitis with eosinophilia syndrome are characterized by tissue eosinophilia and nasal mucosal injury. Recently, it has been shown that the adherence of eosinophils and other leukocytes to epithelial cells is mediated by intercellular adhesion molecule-1 (ICAM-1) and related adherence-promoting glycoproteins. METHODS: In this study we examined the constitutive expression of ICAM-1 on human nasal epithelial cells (HNECs), and the effects of interferon-gamma, tumor necrosis factor-gamma eosinophil major basic protein, and eosinophil cationic protein on the regulation of ICAM-1 expression on these cells. Similar studies were performed with A549 pneumocytes as comparative epithelial cells. RESULTS: Constitutive expression of ICAM-1 was significantly higher on cultured HNECs than on A549 cells, although nasal epithelial cells in tissue specimens did not demonstrate detectable levels of ICAM-1. This spontaneous expression of ICAM-1 on cultured HNECs may explain the unique susceptibility of the nasal mucosa to rhinovirus infection, because ICAM-1 is the epithelial cell receptor for most rhinoviruses. Physiologic concentrations of major basic protein and eosinophil cationic protein stimulated significant upregulation of ICAM-1 on HNECs, which was comparable to that produced by interferon-gamma and tumor necrosis factor-alpha. In contrast, these eosinophil constituents did not stimulate ICAM-1 upregulation on A549 alveolar epithelial cells, although A549 cells did respond to interferon-gamma and tumor necrosis factor-alpha. CONCLUSION: The observation that eosinophil products upregulate ICAM-1 on HNECs suggests a positive feedback mechanism, in which the products released from migrating eosinophils might promote additional HNEC-leukocyte adherence by enhancing interactions between leukocyte beta 2 integrins (CD11/18) and nasal epithelial ICAM-1.

Partial characterization of proteoglycans synthesized by human gingival epithelial cells in culture.

Proteoglycans (PGs) were extracted from the [35S]-sulfate labelled medium and cell layer of proliferating human gingival epithelial cells and analyzed by ion exchange and molecular sieve chromatography, and by SDS-PAGE. The majority of the incorporated radioactivity secreted into the medium eluted from a DEAE Sephacel ion exchange column as a single peak at 0.44 M NaCl with a small shoulder at 0.52 M NaCl. This material, when chromatographed on Sepharose CL-6B contained two species--a quantitatively major peak at K(av) = 0.30 (M(r) congruent to 235,000 on SDS-PAGE) and a quantitatively minor peak at K(av) = 0.39. The major peak was sensitive to alkaline borohydride, shifting to K(av) = 0.45, and nitrous acid degradation, indicating the presence of heparan sulfate PG with glycosaminoglycan chains with M(r) congruent to 26,000. The minor peak is chondroitin/dermatan sulfate PG with glycosaminoglycan chains of M(r) = 22,200 as indicated by sensitivity to alkaline borohydride (shifting to K(av) = 0.48) and chondroitin ABC lyase digestion. The [35S]-sulfate labelled material from the cell layer eluted in a broad peak between 0-0.50 M NaCl from DEAE Sephacel. Chromatography of this material on Sepharose CL-6B revealed the presence of three peaks at K(av) = 0.20, 0.31, and 0.75. The largest peak (K(av) = 0.20 and M(r) congruent to 245,000 on SDS-PAGE) shifted elution position to K(av) = 0.50 after alkaline borohydride treatment and was completely sensitive to nitrous acid degradation. These results indicate that this peak contains heparan sulfate PG with glycosaminoglycan chains of M(r) congruent to 20,000. Two peaks containing [35S]-sulfate labelled glycosaminoglycan chains were detected by chromatography of the cell layer extract over Sepharose CL-6B with K(av)S = 0.42 (M(r) congruent to 30,500) and 0.75 (M(r) congruent to 5300). The larger peak was predominantly chondroitin/dermatan glycosaminoglycan as indicated by susceptibility to chondroitin ABC lyase while the chains at K(av) = 0.75 were predominantly heparan sulfate with 83% susceptibility to nitrous acid. These results indicate that cultured human gingival epithelial cells synthesize and secrete principally heparan sulfate PGs with small amounts of chondroitin/dermatan sulfate PGs. This work will serve as a basis for future studies designed to examine those factors involved in regulation of PG synthesis by these cells.

Once-a-day dosing with theophylline: a comparison of four sustained-release products.

This study compared once-a-day dosing of Slo-bid, Theo-Dur, Theo-24 and Uniphyl, sustained release theophylline preparations, in the treatment of 12 mild to moderate asthmatic patients (FEV1 greater than 60%). Eight hundred milligrams was given once-a-day in the morning for 2 weeks for each drug in this 4-way, crossover, open-label study. At the end of each 2-week period, pharmacokinetics were assessed by measuring theophylline levels every two hours for 24 hours. Efficacy was evaluated by spirometry, physical examination, daily peak flow measurements, and daily symptom diaries. In an additional 2-week period, Slo-bid 800 mg, was taken once-a-day after the evening meal and the same measures of pharmacokinetics and efficacy were performed. Slo-bid (range 8.8, coefficient variation 19.5) exhibited significantly less intrapatient variability than Theo-Dur (range 12.2, coefficient of variation 36.5) and Theo-24 (range 8.2, coefficient of variation 25.8). Patients taking Slo-bid also had significantly better evening peak flow values than patients taking Theo-Dur (424.5 L/min versus 395.4 L/min). Analysis of other measures of theophylline pharmacokinetics (area under the curve, minimum serum level, occupancy times) as well as diary variables, physical examination findings, and spirometry values showed no differences among the four formulations, although expected individual variability in pharmacokinetics was observed. When Slo-bid was dosed in the evening, higher blood levels were achieved compared with morning administration, suggesting a therapeutic advantage of evening dosing with this product.

Adrenal function in adult asthmatics during long-term daily treatment with 800, 1,200, and 1,600 micrograms triamcinolone acetonide. Multicenter study.

A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.

Neutrophil-mediated damage to human gingival epithelial cells.

Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of inflammatory gingivitis and periodontitis. To further study the role of PMNs in mediating gingival injury, we cocultured these cells in vitro with monolayers of human gingival epithelial cells. Scanning electron microscopy revealed that the epithelial cells were homogeneous and SDS-PAGE/immunoblot analysis identified the presence of keratins K3, K13 and the K6/16 pair which authenticated the oral origin of the cells. Injury to the gingival cells was determined by scanning electron microscopy and measurement of cell detachment and cytolysis. Unstimulated PMNs produced minimal lysis or detachment, but PMNs stimulated by phorbol myristate acetate produced marked epithelial cell detachment without lysis, which was time- and PMN-dose-dependent. Supernatants of activated PMNs were similarly effective, indicating that the mediator was a stable soluble substance. Elastase and cathepsin G, two neutral proteases of PMN origin, produced time- and concentration-dependent detachment of gingival epithelial cells, suggesting that these enzymes may mediate this form of injury. In other studies, gingival epithelial cells were exposed to PMN myeloperoxidase (MPO), chloride and glucose plus glucose oxidase (GO) as a hydrogen peroxide (H2O2) generating system. The toxic oxygen species produced by this system caused lysis of the epithelial targets which was dependent on the duration of incubation and the concentrations of MPO and GO. Azide, an inhibitor of MPO, and catalase, a scavenger of H2O2, inhibited the lytic activity of this system. Scanning electron micrographs of gingival epithelial cells cocultured with activated PMNs showed lifting of the cells from the plating surface, while target cells attacked by the MPO system revealed extensive damage of cell membranes. These studies indicate that activated PMNs cause nonlytic detachment injury to gingival epithelial cells which may be mediated by digestion of their extracellular matrix by granule neutral proteases. Furthermore, PMN MPO is capable of generating toxic oxygen species which can lyse these epithelial cells. Collectively, these actions could have profound adverse effects on the function and integrity of the gingival epithelium.

Acute consumption of C1 inhibitor in a patient with acquired C1-inhibitor deficiency syndrome.

Acquired C1-inhibitor (C1 INH) deficiency is usually found in association with an underlying disease that is believed to be responsible for increased C1 INH catabolism, ultimately leading to the development of C1 INH deficiency. We report a remarkable patient with acquired C1 INH deficiency in whom a unique progression of complement- and contact-system abnormalities has been observed. S. G. suffers from recurrent episodes of angioedema and hypotension. Results of repeated complement studies were initially normal, and the patient was diagnosed as having idiopathic anaphylaxis. Two years later, the patient was found to develop acute consumption of C1 INH with activation of the complement and contact systems during episodes of angioedema. The patient continued to have normal C1 INH levels and to have no evidence for complement- or contact-system activation between attacks of angioedema. One year later, her course evolved into a more typical course for acquired C1 INH deficiency consisting of continuously low functional C1 INH levels with evidence of activation of the complement and contact systems. S. G. provides a unique insight into the development of acquired C1 INH deficiency.

Depression and panic attacks related to phenol-formaldehyde composite material exposure in an aerospace manufacturing plant.

In a case series study we evaluated 53 composite-materials workers in an aerospace plant who filed workers' compensation claims for illness allegedly related to phenol-formaldehyde resin exposure. Symptoms ranged from mucosal and skin irritation to depression and cognitive impairment. Certain health practitioners implying they had immunologic dysfunction and organic brain injury, led workers to believe they were chemically poisoned. Industrial hygiene evaluation failed to show levels of chemicals above permissible levels. Thorough evaluation by our multidisciplinary panel failed to find significant objective abnormalities by physical exam and laboratory testing. Thirty-nine percent of the workers had sensory irritation and/or skin complaints that generally resolved rapidly with removal from exposure. Psychiatric diagnoses (including major depression and/or panic attacks) were made in 74% of the workers, but only 26% of these had antecedent disease. Fourteen (26%) had multiple somatic complaints that generally persisted despite removal from exposure, but they also had long histories of significant pre-existing psychological illness. Detailed neuropsychologic testing failed to show any definite evidence or organic brain dysfunction in any of the workers tested. We speculate that sensory irritation from low-level volatile organic compounds with autonomic arousal, reinforced by the belief they were "chemically poisoned," led to psychogenic illness.

Effects of albuterol and procaterol on exercise-induced asthma.

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.

Clinical and immunologic evaluation of 37 workers exposed to gaseous formaldehyde.

Thirty-seven workers exposed to formaldehyde (F) were evaluated to determine whether any of their respiratory or ocular symptoms were mediated by an immunologic response to F. Because there has never been a case of defined immunologically mediated respiratory or ocular disease as a result of exposure to gaseous F, we used clinical and immunologic criteria developed for immunologic respiratory diseases that result from inhalational exposure to trimellitic anhydride. A clinical assessment included review of a medical summary of history, physical examination, chest x-ray films, and pulmonary function studies. Serologic assessment was made with an ELISA for IgE and IgG to F human serum albumin. The final evaluation for immunologically mediated disease was based on both the clinical and serologic assessments. None of the workers had IgE or IgG antibody to F-human serum albumin or an immunologically mediated respiratory or ocular disease caused by F; however, some of the workers appeared to experience irritant symptoms caused by workplace exposure to F or other irritant chemicals.