Comparison of clinic models for patients with work-related asthma.

BACKGROUND: Work-related asthma (WRA) is a prevalent occupational lung disease that is associated with undesirable effects on psychological status, quality of life (QoL), workplace activity and socioeconomic status. Previous studies have also indicated that clinic structure may impact outcomes among patients with asthma. AIMS: To identify the impact of clinic structure on psychological status, QoL, workplace limitations and socioeconomic status of patients with WRA among two different tertiary clinic models. METHODS: We performed a cross-sectional analysis between two tertiary clinics: clinic 1 had a traditional referral base and clinical staffing while clinic 2 entirely comprised Worker's Compensation System referrals and included an occupational hygienist and a return-to-work coordinator. Beck Anxiety and Depression II Inventories (BAI and BDI-II), Marks' Asthma Quality of Life Questionnaire (M-AQLQ) and Work Limitation Questionnaire (WLQ) were used to assess outcomes for patients with WRA. RESULTS: Clinic 2 participants had a better psychological status across the four instruments compared with clinic 1 (for Beck 'Anxiety': P < 0.001 and 'Depression': P < 0.01, 'Mood' domain of M-AQLQ: NS and 'Mental Demands' domain of WLQ: P < 0.01). Clinic 2 had a greater proportion of participants with reduced income. CONCLUSIONS: Our study indicates that clinic structure may play a role in outcomes. Future research should examine this in larger sample sizes.

Salicylate activity. 1. Protection of plants from paraquat injury.

Paraquat (1,1'-dimethyl-4,4'-bipyridinium; methylviologen) is a widely used, nonselective contact herbicide that rapidly stimulates free radical generation. It has been found that the addition of sodium salicylate (sodium 2-hydroxybenzoate; NaSA) to paraquat spray solutions significantly decreased herbicidal activity. This protection was observed in tobacco (Nicotiana tabacum) regardless of whether NaSA was foliar-applied along with or prior to paraquat application or NaSA was soil-applied prior to paraquat application. Because salicylic acid (SA) is an inducer of systemic acquired resistance (SAR) to plant disease, paraquat protection by three SAR inducers (acibenzolar-S-methyl, harpin, and probenazole) and selected salicylate derivatives was assessed. Twenty-two of 24 compounds tested decreased herbicidal activity when foliar-applied with paraquat. Protection from paraquat was greatest with 5-chlorosalicylate, and no protection was observed with benzoic acid. NaSA decreased paraquat activity on npr1-2, an Arabidopsis mutant that is compromised in NaSA-induced SAR, and on ein2-1, an ethylene-insensitive Arabidopsis mutant. Thus, salicylate protection from paraquat is independent of disease resistance and ethylene perception. This suggests the existence of an NaSA-mediated pathway capable of protecting plants from reactive oxygen stress.

Salicylate activity. 2. Potentiation of atrazine.

Atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine] inhibits photosystem II (PSII) and is commonly used to control weeds in maize. It has been found that addition of sodium salicylate (sodium 2-hydroxybenzoate; NaSA) increased the postemergence herbicidal activity of atrazine against dicotyledonous weeds. NaSA also potentiated the activity of bentazon, another PSII-inhibiting herbicide. NaSA increased atrazine activity when applied either as a tank mix or up to 96 h prior to atrazine application. Other salicylates and the plant disease resistance inducers acibenzolar-S-methyl [benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester] and 2,6-dichloroisonicotinic acid also increased atrazine activity. Among the compounds tested, 3-chloro-5-fluorosalicylate, 4-chlorosalicylate, or 2,6-dichloroisonicotinic acid combined with atrazine yielded the greatest increase in herbicidal activity. Potentiation of atrazine by NaSA was greater at higher temperatures (35 and 25 > 15 degrees C). Also, greater potentiation was observed as the light level decreased. In darkness, NaSA alone or in combination with atrazine caused plant death, whereas atrazine alone had little effect. NaSA increased atrazine activity on npr1-2, an Arabidopsis mutant compromised in SA-induced disease resistance. Atrazine activity was also potentiated by NaSA on the ethylene insensitive mutant ein2-1. This indicates that atrazine potentiation is independent of either salicylate-induced disease resistance or ethylene perception.

Salicylate activity. 3. Structure relationship to systemic acquired resistance.

Salicylic acid (2-hydroxybenzoic acid; SA) is a primary signal inducing plant defenses against pathogens. This plant disease resistance, known as systemic acquired resistance (SAR), is an attractive target for the development of new plant protection agents. SAR induction is a multistep process that includes accumulation of pathogenesis-related (PR) proteins. The structure-activity profile of salicylates and related compounds has been evaluated using an inducible PR protein (PR-1a) and plant resistance to tobacco mosaic virus (TMV) as markers. Among the 47 selected monosubstituted and multiple-substituted salicylate derivatives tested, all 8 derivatives that induced more PR-1a protein than SA were fluorinated or chlorinated in the 3- and/or 5-position (3,5-difluorosalicylate > 3-chlorosalicylate > 5-chlorosalicylate > 3,5-dichlorosalicylate > 3-chloro-5-fluorosalicylate > 3-fluorosalicylate > 3-fluoro-5-chlorosalicylate > 3,5-dichloro-6-hydroxysalicylate > SA). In general, substitutions for or on the 2-hydroxyl group or at the 4-position of the ring reduced or eliminated PR-1a protein induction. In contrast, substitutions in positions ortho (3-position) or para (5-position) to the hydroxyl group with electron-withdrawing groups other than chlorine or fluorine decreased induction, and electron-donating groups in these positions also had a deleterious effect on PR-1a induction. PR-1a protein accumulation and reduction in TMV lesion diameter exhibited a log-linear relationship. The seven salicylate derivatives that were the most active TMV resistance inducers were all halogenated in the 3- and/or 5-position (3-chlorosalicylate > 3,5-difluorosalicylate > 3,5-dichloro-6-hydroxysalicylate > 3,5,6-trichlorosalicylate > 5-chlorosalicylate > 5-fluorosalicylate > 3,5-dichlorosalicylate > 4-fluorosalicylate > 3-fluorosalicylate > 3-chloro-5-fluorosalicylate > 4-chlorosalicylate > SA). The correlation between PR-1a protein induction and resistance to TMV confirms the value of using PR-1a induction as a screening tool for developing new plant disease control agents.

DNA topoisomerase I in the mouse central nervous system: Age and sex dependence.

Topoisomerase I (topo I) is a nuclear enzyme responsible for the topological state of DNA and therefore participates in most DNA transactions, particularly in transcription. Topo I, a ubiquitous enzyme, was identified and characterized in various cell types and tissues; however, the characterization of topo I in the intact central nervous system was not performed. Here we investigated, for the first time, the activity, level, and distribution pattern of topo I in the various selected brain regions in the mouse. In the visual cortex, cerebellum, and striatum the activity of topo I was 3-4-fold higher compared to that found in the hippocampus and hypothalamus. Immunohistochemical and immunofluorescence analyses revealed specific distribution patterns of topo I protein in neurons of each of the areas examined. The highest topo I levels were observed in inhibitory neurons. In addition to the expected nuclear localization of this protein, some neurons exhibited significant cytoplasmic content as well. The activity and level of topo I is age- and gender-dependent. It increases from birth to maturity and decreases, more significantly in males, with senescence. These results point to a possible importance and involvement of topo I activity and regulation in various brain functions.

Psychological features of subjects with idiopathic environmental intolerance.

OBJECTIVES: Idiopathic environmental intolerance (IEI) is associated with unexplained symptoms attributed to non-noxious levels of environmental substances. Clinically, some of the symptoms of IEI overlap with those of panic disorder (PD). We have recently reported a link between IEI and panic responses to a single inhalation of 35% carbon dioxide (CO(2)), a reliable panic induction challenge. This study assessed depression, stress, anxiety, and agoraphobic symptoms among IEI subjects from our previous study versus healthy controls. METHODS: Thirty-six IEI and 37 control subjects with no preexisting psychiatric history were compared on self-report psychological questionnaires. RESULTS: IEI subjects scored significantly higher than controls on the Agoraphobic Cognitions Questionnaire (ACQ), Depression Anxiety Stress Scales (DASS), and Mobility Inventory for Agoraphobia (MI) (Student's t, P<.05). CONCLUSIONS: IEI subjects represent a group with morbidity significantly higher than a control population but less than what would be expected for a clinical psychiatric population.

Post-coma paraschizophrenia and quality of life in patients with closed-head injuries.

Background. Organic brain damage is traditionally an excluding criteria for a psychiatric diagnosis of mental illness. In fact, however, the neurobehavioral disturbances exhibited by many CHI patients, especially those who have been comatose for more than a month, are strikingly similar to the symptoms of Type II schizophrenia. The authors propose to use the term "post-coma paraschizophrenia" to describe these disturbances and discuss their negative impact on the quality of life of CHI patients.
Material and methods. The experimental group (Group CHI) consisted of 15 CHI patients, 7 males and 8 females, ranging in age from 17 to 58, treated in the Department of Medical Rehabilitation at the Cracow Rehabilitation Center and the Rehabilitation Clinic at the Bydgoszcz Medical University. All these patients had incurred a closed-head injury resulting in a coma lasting at least one month. He control group (Group SCHI) consisted of 15 patients diagnosed with Type II schizophrenia, matched by age, sex, and level of education to the patients in Group CHI, under treatment in the Psychiatry Department at the Wroclaw Medical University and the Bydgoszcz Medical University. The data reported were based on clinical observation, patient and family interviews, standard neuropsychological tests, the Frontal Behavioral Inventory, and the Quality of Life Scale for Patients with Traumatic Brain Injuries.
Results. Standard neuropsychological tests showed similar dysfunctions in general intelligence and memory, with a tendency in both groups to lower scores in non-verbal parameters. Some interesting qualitative differences in performance are presented. All the CHI patients showed significant signs of frontal syndrome, with a profile resembling fronto-temporal dementia, while the test results from the SCHI patients were more similar to those associated with severe clinical depression. All of the patients in the CHI group exhibited at least some of the symptoms traditionally regarded as indicative of schizophrenia. Positive (formative) symptoms of schizophrenia were found much more often in the patients from Group SCHI, whereas the percentages for the occurrence of particular negative (defective) symptoms are quite similar in both groups.
Conclusions. Patients with closed-head injuries may present with quasi-psychotic symptoms, here termed "post-coma paraschizophrenia". Among the most significant common features of the two syndromes are disorganized behavior, apathy, and disturbances of executive functions. Post-coma paraschizophrenia, which mostly remains untreated because of the lack of neuropsychiatric diagnosis, has a significant negative on the quality of life of CHI patients, and should receive further attention in both theoretical research and clinical practice.

"Towards a Better Life": a program of comprehensive rehabilitation for elderly patients following revision hip arthroplasty.

Introduction. The aim of the research was to evaluate the quality of life of patients recovering from revision hip arthroplasty, who underwent rehabilitation under the "Towards a Better Life" program (TBL). In the TBL Program, appropriate physical exercises, relaxation techniques, seminars, and panel discussions are combined to support general improvement in both physical and psychological condition, thus improving the patients' quality of live.
Material and methods. The effectiveness of the TBL approach was evaluated in a clinical experiment involving 36 patients recovering from revision hip arthroplasty, treated under the standard rehabilitation program in general use at the centers represented by the authors. The patients were divided into two equal groups, matched by age and sex: an experimental group E (n = 18), with patients who received additionally the "Towards a Better Life" Program, and a control group K (n = 18), consisting of patients who did not receive this program. The methods used to evaluate the outcome of rehabilitation included clinical interview and observation, the Medical Outcomes Study (MOS-100) and the Self-Evaluating Quality of Life Scale (QOL). The patients were tested before rehabilitation commenced and re-tested two months later.
Analysis of results. On the Physical Index of the MOS-100 scale considerably greater progress was observed in patients from Group E in terms of reduced pain, increased coordination and fluency of movement, improved respiratory capacity, regulation of blood pressure and pulse, functioning of the digestive system, reduced body weight, and improved walking distance. In this group somewhat greater improvements were noted on the Psychological Index of the MOS-100, especially in cognitive functions (perception and attention) and emotional factors (increased satisfaction with life, reduced anexiety, depression, and irritability). The QOL parameters most sensitive to the difference between the TBL Program and the standard program were pain management, independence and self-care, and especially improved self-image and reduced anxiety. The improvements noted by Group E were in many subtest two or three times higher than in Group K.
Conclusions. The greater improvements recorder by patients participating in the "Towards a Better Life" Program in all measured parameters indicates that the program is highly effective in comparison to the standard model. The patients from Group E were much more satisfied with the results they had achieved in rehabilitation, and attained a higher degree of independence and self-determination. The TBL Program can be used to improve the quality of life of patients recovering from revision hip arthroplasty.

Cyclooxygenase metabolites play a different role in ozone-induced pulmonary function decline in asthmatics compared to normals.

Indomethacin has been used to demonstrate that cyclooxygenase (COX) metabolites of arachidonic acid play a mechanistic role in ozone-induced spirometric decline in normals (Nm). Since the weight of evidence suggests that asthmatics (Asth) do not differ substantially from Nm subjects in the magnitude of their spirometric response to ozone, we sought to determine whether COX metabolites play a similar role in the asthmatic response to ozone. Thirteen (n = 13) Asth and nine (n = 9) Nm volunteers were pretreated with indomethacin or placebo (3 days, 75 mg/day), then exposed for 2 h to 400 ppb ozone or clean air while performing mild intermittent exercise (Vi(min) = 30 L/min.). Baseline changes in spirometry (FVC, FEV(1), FEF(25), FEF(50), FEF(60p), FEF(75)) and soluble markers of COX metabolism (prostaglandin [PG] F2-alpha) were measured from induced sputum samples. Results showed similar reductions in FVC (Asth = 12%, Nm = 10%) and FEV(1) (Asth = 13%, Nm = 11%) in Asth and Nm following ozone. Variables representing small-airways function demonstrated the greatest ozone-induced decline in Asth (FEF(75) = 25%). Indomethacin pretreatment significantly attenuated ozone-induced decreases in FVC and FEV(1) in Nm, but not in Asth. Marked attenuation of ozone-induced decrements in FEF(75) and FEF(60p) was observed in Asth but not in Nm. PGF2-alpha levels were similar in both groups prior to ozone exposure with indomethacin (Asth = 65 pg/ml, Nm = 59 pg/ml), but postexposure levels in Asth were significantly elevated (118 pg/ml) compared to Nm (54 pg/ml). We conclude that COX metabolites, such as PGF2-alpha, play an important but different role in asthmatics than normals with respect to ozone-induced pulmonary function decline. Specifically, COX metabolites contribute to restrictive-type changes in normals and obstructive-type changes in small airways in asthmatics.

Asthmatic subjects symptomatically worse at work: prevalence and characterization among a general asthma clinic population.

STUDY OBJECTIVES: To assess the prevalence of a historical occupational component to asthma in an adult asthma clinic and to compare characteristics of asthmatic subjects with and without work-attributed symptoms. DESIGN: A retrospective review of data obtained from a physician-administered questionnaire, answers to which were obtained at the initial patient visit of asthmatic subjects, and which included specific questions regarding the relationship of work to symptoms. Chart review data were used to supplement information on workplace exposures and investigations. SETTING: A university-based secondary- and tertiary-referral asthma clinic. PATIENTS: Seven hundred thirty-one adult asthmatic subjects who were referred for assessment and management of asthma. INTERVENTIONS: Statistical analyses of asthmatic subjects with and without work-attributed symptoms and a determination, from chart review, of the likelihood of causes for symptomatic worsening of asthma at work. MEASUREMENTS AND RESULTS: Sixty percent of the patients (435) had adult onset of asthma, among whom 310 patients (71%) were employed at the time of their visit. Fifty-one patients reported their asthma to be worse at work (ie, 16% of adult-onset working asthmatic subjects). Sixteen of these patients (31%) had likely or possible sensitizer-induced occupational asthma (OA), and 49% likely had aggravation of underlying asthma. The other 20% of patients had possible OA or aggravation of underlying asthma at work. CONCLUSIONS: Adult-onset asthmatic subjects commonly report a worsening of asthma at work, more commonly on the basis of likely aggravation of underlying asthma than on the basis of likely or possible OA.

Uncoupling salicylic acid-dependent cell death and defense-related responses from disease resistance in the Arabidopsis mutant acd5.

Salicylic acid (SA) is required for resistance to many diseases in higher plants. SA-dependent cell death and defense-related responses have been correlated with disease resistance. The accelerated cell death 5 mutant of Arabidopsis provides additional genetic evidence that SA regulates cell death and defense-related responses. However, in acd5, these events are uncoupled from disease resistance. acd5 plants are more susceptible to Pseudomonas syringae early in development and show spontaneous SA accumulation, cell death, and defense-related markers later in development. In acd5 plants, cell death and defense-related responses are SA dependent but they do not confer disease resistance. Double mutants with acd5 and nonexpressor of PR1, in which SA signaling is partially blocked, show greatly attenuated cell death, indicating a role for NPR1 in controlling cell death. The hormone ethylene potentiates the effects of SA and is important for disease symptom development in Arabidopsis. Double mutants of acd5 and ethylene insensitive 2, in which ethylene signaling is blocked, show decreased cell death, supporting a role for ethylene in cell death control. We propose that acd5 plants mimic P. syringae-infected wild-type plants and that both SA and ethylene are normally involved in regulating cell death during some susceptible pathogen infections.

Induced sputum: comparison of postinfectious cough with allergic asthma in children.

BACKGROUND: Cough persisting after a respiratory infection is common in children and is often managed as asthma. However, little is known about the pathophysiologic mechanisms of such cough and how it compares with asthma. OBJECTIVE: We used the technique of induced sputum to examine the inflammatory index values associated with persistent cough or allergic asthma in children. We hypothesized that the sputum from children with persistent postinfectious cough would differ from that of children with allergic asthma in that the former would lack eosinophils compared with the latter. STUDY DESIGN: Sputum production was induced with hypertonic saline solution in 34 children: 12 with cough persisting for 1 month or more after an apparent respiratory tract infection, not treated with corticosteroid; 11 with untreated atopic asthma, not using inhaled corticosteroid; and 11 with treated atopic asthma using inhaled corticosteroid. RESULTS: The percentage of eosinophils in the sputum of children with cough was significantly lower than in the sputum of children with untreated allergic asthma (median 0.5% vs 14.5%, P <.0001). Similarly, the percentage of eosinophils in the sputum of children with asthma treated with inhaled steroids was significantly lower compared with untreated asthmatic children (1.5% vs 14.5%, P <.0001). The peripheral blood eosinophils, serum eosinophil cationic protein, and nasal percent eosinophils of the patients with cough were also significantly lower than those from patients with untreated asthma. Methacholine challenge in 6 of the 11 cough patients tested showed mild-to-moderate hyperresponsiveness, whereas the other 5 had a negative methacholine challenge. CONCLUSIONS: Children with persistent postinfectious cough do not have airway eosinophilia typical of untreated asthma. Despite the absence of eosinophilic inflammation, some of the patients with chronic cough had reactive airways. These results suggest that postinfectious cough in children has different pathophysiologic features than allergic asthma and probably represents a different disease.

Carbon dioxide inhalation challenges in idiopathic environmental intolerance.

BACKGROUND: Idiopathic environmental intolerance (IEI) is associated with unexplained physical symptoms, which overlap considerably with those of panic disorder (PD). OBJECTIVE: This study tested the hypothesis that patients with symptoms to suggest IEI exhibit features of PD in response to nonnoxious environmental stimuli. METHODS: A single-blind, case-control 35% carbon dioxide inhalation challenge was conducted at a university-based occupational health unit with the use of standardized psychologic questionnaires involving 36 patients with IEI and 37 healthy control subjects. The main outcome measures included panic attack symptoms and scores on the Anxiety Sensitivity Index, a measure of panic-related anxiety. RESULTS: Patients with IEI scored significantly higher on the Anxiety Sensitivity Index than control subjects did (P <.05). Significantly more patients with IEI (71%) than control subjects (26%) fulfilled panic attack criteria after carbon dioxide (P <.001). Physiologic responses to the challenge were not significantly different between groups. CONCLUSIONS: Results suggest that, similar to patients with PD, patients with IEI display high anxiety sensitivity and in response to carbon dioxide inhalation tend to experience heightened anxiety and panic attacks.

A comparison of biomarkers of ozone exposure in human plasma, nasal lavage, and sputum.

We examined ozone-induced upper and lower airway inflammatory responses and the concentrations of hydroxylated salicylate metabolites using nasal lavage fluid and induced sputum, in order to identify noninvasive and sensitive biomarkers for ozone exposure and effects. A time course for plasma concentration of 2, 3-dihydroxybenzoic acid (2,3-DHBA, a salicylate metabolite and an indicator for hydroxyl radical) in response to 0.12 ppm ozone was also studied. Healthy, young, nonsmoking volunteers were given acetylsalicylic acid (ASA, 975 mg) or placebo orally. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Blood was collected hourly over a 4-h period. After exposure, nasal lavage fluid was collected, and sputum was induced using hypertonic saline. Results show that in sputum the percentage of neutrophils was significantly higher after the subjects were exposed to 0.4 ppm ozone (p<.05) than after they were exposed to filtered air or 0.12 ppm ozone. The absolute number and the percentage of macrophages were significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The percentage of lymphocytes in sputum was also significantly lower at 0.4 ppm ozone than for filtered air control or 0.12 ppm ozone. The sputum cellular responses to ozone were not significantly altered by ASA treatment. In nasal lavage, cell counts and differentials did not change significantly after exposure to ozone in comparison to filtered air control. The cellular data indicate an acute inflammation developed during ozone exposure in the lower respiratory tract. The concentrations of total protein and interleukin-8 and the activity of N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) in nasal lavage and sputum did not change significantly following exposure to ozone in comparison to filtered air control. Plasma 2,3-DHBA concentration increased significantly following exposure to 0.12 ppm ozone in an exposure-dependent temporal pattern. Salicylate metabolites in nasal lavage fluid and sputum did not increase significantly following exposure to ozone. There was a marked variation of 2,3-DHBA concentrations in airway fluids. Data suggest that plasma 2,3-DHBA is a sensitive marker indicating acute ozone exposure, even at an ozone concentration that causes minimal observable airway effects in healthy subjects.

Effect of exposure to low levels of ozone on the response to inhaled allergen in allergic asthmatic patients.

STUDY OBJECTIVES: In a previous study published by our group, six out of nine subjects with mild allergic asthma were shown to have an enhanced response to allergen challenge following a 1-h exposure in an 0.8-m3 exposure chamber (modified from a body plethysmograph) to an average of 120 parts per billion (ppb) ozone at rest. Other studies failed to confirm this effect. In the present study, using a similar design, we reexamined this effect using a larger group of asthmatics and a larger chamber allowing minimal fluctuations in ozone levels during exposures. DESIGN: Prospective, randomized single-blinded crossover study. SETTING: Pulmonary function laboratory equipped with an exposure chamber. SUBJECTS: Fifteen subjects had mild allergic asthma; 9 men and 6 women; the mean (SD) age was 32.5 (10) years; FEV1 was 3.4 (0.8) L; baseline methacholine provocation concentration causing a 20% fall in FEV1 was (PC20) 3.28 (4.1) mg/mL. INTERVENTIONS: Each participant was exposed, at rest, on 1 day to filtered air and on another day to ozone (mean level=120 ppb) in a larger exposure chamber than the one used in our first study with less variability in ozone level (110 to 130 vs 85 to 175 ppb) using a random, single-blinded design. After each exposure, the subject was challenged with allergen (nine with grass pollen extract and six with ragweed extract) and allergen PC15 was measured. RESULTS: Ozone preexposure did not affect allergen PC15 when compared with clean air preexposure (allergen PC15 dilution 1/114 vs 1/119, respectively). Ozone vs air preexposure resulted in an allergen PC15 that was lower in five subjects, higher in six, and unchanged (within one doubling dose) in four. CONCLUSIONS: At this low level with less variability and lower peaks than our previous study, ozone had no significant effect on airway allergen responsiveness.

In vivo salicylate hydroxylation: a potential biomarker for assessing acute ozone exposure and effects in humans.

Ozone is known to yield hydroxyl radical, which may contribute to ozone-mediated lung injury. In the presence of hydroxyl radical, salicylate is hydroxylated to form 2,3-dihydroxybenzoic acid (2,3-DHBA). There is no evidence of enzymatic formation of 2,3-DHBA. We hypothesized that salicylate hydroxylation might be used as a biomarker indicating human exposure to ozone. Healthy, nonsmoking volunteers, 18 to 34 yr of age, were given acetylsalicylic acid (975 mg) or placebo orally 0.5 h before an exposure. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Results indicate significant decrements in FVC, FEV1.0, forced expiratory flows at 50% and 75% of FVC, and peak expiratory flow rate, and an increase in airway resistance, after exposure to 0.4 ppm ozone in comparison with air control (p < 0.05). Exposure to 0.4 ppm ozone also resulted in increased symptom numbers and severity (p < 0.05). When subjects were exposed to 0.12 ppm ozone, changes of pulmonary function and symptoms reported were minimal. Plasma concentration of 2,3-DHBA was significantly increased after exposure to 0.12 and 0.4 ppm ozone in comparison with air control (p < 0.05). There was a significant correlation between ozone-induced changes of pulmonary function and normalized salicylate hydroxylation (p < 0.05). The results indicate that exposure to ozone can initiate in vivo production of hydroxyl radical, a potent reactive agent. Salicylate hydroxylation may then serve as a sensitive dosimetric biomarker for ozone exposure, even at subclinical ozone exposure levels.