Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma.

Ozone exposure aggravates asthma, as has been demonstrated in both controlled exposures and epidemiologic studies. In the current double-blind crossover study, the authors evaluated the effects of dietary antioxidants (i.e., 400 IU vitamin E/500 mg vitamin C) on ozone-induced bronchial hyperresponsiveness in adult subjects with asthma. Seventeen subjects were exposed to 0.12 ppm of ozone or to air for 45 min during intermittent moderate exercise. Bronchial hyperresponsiveness was assessed with 10-min sulfur dioxide (i.e., 0.10 ppm and 0.25 ppm) inhalation challenges. Subjects who were given dietary antioxidants responded less severely to sulfur dioxide challenge than subjects given a placebo (i.e., forced expiratory volume in the 1st sec: -1.2% vs. 4.4%, respectively; peak flow: +2.2% vs. -3.0%, respectively; and mid-forced expiratory flow: +2.0% vs. -4.3%, respectively). Effects were more pronounced when subjects were grouped by response to sulfur dioxide at the screening visit. The results suggest that dietary supplementation with vitamins E and C benefits asthmatic adults who are exposed to air pollutants.

Genetic polymorphisms as biomarkers of sensitivity to inhaled sulfur dioxide in subjects with asthma.

BACKGROUND: Individuals with asthma are sensitive to inhaled sulfur dioxide (SO2); decrements in pulmonary function occur after exposure to low concentrations even for a short duration of time. There is a great amount of interindividual variation in response to SO2. OBJECTIVE: It was our objective to determine whether one of the following polymorphism locations linked with asthma is associated with the bronchial hyperresponsiveness to SO2 observed in some asthmatic patients: the beta2-adrenergic receptor, interleukin-4 (IL-4) receptor alpha subunit, Clara cell secretory protein (CC16), TNF-alpha gene promoter, and first intron of the lymphotoxin alpha (LT-alpha) gene. METHODS: Subjects were volunteers with physician-diagnosed asthma requiring regular asthma medication. Spirometry was performed before and after a 10-minute exposure to 0.5 ppm SO2. Subjects were classified as SO2 responders if forced expiratory volume in 1 second (FEV1) decreased > or = 12%. DNA obtained from buccal cell samples was analyzed for genetic polymorphisms. RESULTS: Of the 62 subjects (21 male and 41 female), 13 had a 12% or greater decrement in FEV1 after SO2 exposure (range + 19% to -49%). Response to SO2 was associated with the wild-type allele of the TNF-alpha promoter polymorphism (12 of 12 SO2 responders versus 28 of 46 nonresponders; P < .05) but with no other polymorphisms. Medication category and atopic status showed no association with SO2 sensitivity. CONCLUSIONS: The wild-type allele of the TNF-alpha promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO2.

Sulphur dioxide sensitivity and plasma antioxidants in adult subjects with asthma.

OBJECTIVES: To screen adult subjects with asthma for sensitivity to inhaled sulphur dioxide (SO2) and identify subject characteristics associated with that sensitivity. Medication use, symptoms, and plasma antioxidant nutrients between SO2 responders and non-responders were compared. METHODS: Adult subjects (ages 18-39 years) with asthma were exposed to 0.5 ppm SO2 for 10 minutes during moderate exercise. Pulmonary function tests and symptom ratings were assessed before and after exposure (n = 47). A subject was classified as sensitive to SO2 if forced expiratory volume in 1 second (FEV1) showed a drop > or = 8% over baseline. Blood samples were obtained from subjects (n = 38) before the SO2 challenge; plasma ascorbate, alpha-tocopherol, retinol, carotenoids, and lipids were measured. RESULTS: Of the 47 subjects screened, 53% had a drop in FEV1 > or = 8% (ranging from -8% to -44%). Among those 25 subjects, the mean drop in FEV1 was -17.2%. Baseline pulmonary function indices (FEV1% of predicted and FEV1/FVC% (forced vital capacity)) did not predict sensitivity to SO2. Although use of medication was inversely related to changes in pulmonary function after SO2 (p < 0.05), both SO2 responders and non-responders were represented in each medication category. Total symptom scores after exposure were significantly correlated with changes in FEV1 (p < 0.05), FVC (p < 0.05), and peak expiratory flow (PEF) (p < 0.01) but not forced expiratory flow between 25% and 75% vital capacity (FEF25-75). Plasma beta-carotene concentrations were inversely associated with PEF values and ascorbate concentrations were inversely associated with FEV1 and FEV1/FVC (p = 0.05 in all cases). High density lipoprotein concentrations were positively correlated with FEV1% of predicted (p < 0.05) and inversely correlated with change in FEF25-75 (p < 0.05) after SO2. CONCLUSION: These results show that the response to SO2 among adults with mild to moderate asthma is very diverse. Severity of asthma defined by medication category was not a predictor of sensitivity to SO2. Lung function values were associated with beta-carotene and ascorbate concentrations in plasma; however, plasma antioxidant nutrient concentrations were not associated with sensitivity to inhaled SO2.

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction.

BACKGROUND: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma. OBJECTIVES: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction. METHODS: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results. RESULTS: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P /=0.5-unit change from baseline; P

Inflammatory effects of ozone in the upper airways of subjects with asthma.

The objective of this study was to determine whether exposure to ozone causes inflammatory or functional changes in the upper or lower airways of asthmatic and nonasthmatic individuals. Ten asthmatic and eight nonasthmatic subjects were exposed to clean air, 120 ppb ozone, or 240 ppb ozone for 90 min during intermittent moderate exercise using a head dome exposure system. Pulmonary function tests, posterior rhinomanometry, and nasal lavage were performed before and after exposure. Leukocyte counts and chemotactic factors leukotriene B4 (LTB4), platelet-activating factor (PAF), and interleukin-8 (IL-8) were analyzed from nasal lavage fluid. In subjects with asthma, a significant increase (p < 0.05) in the number of white blood cells in lavage fluid was detected both immediately and 24 h after exposure to 240 ppb ozone, as was a significant increase in epithelial cells immediately after exposure (p < 0.05). No significant cellular changes were seen in nonasthmatic subjects. A significant correlation was observed between IL-8 and white blood cells counts after exposure to 240 ppb ozone (r = 0.76) in asthmatic subjects. No significant changes in pulmonary or nasal function or biochemical mediators were found in either the asthmatic or nonasthmatic subjects. These data indicate that asthmatic individuals are more sensitive to the acute inflammatory effects of ozone than nonasthmatic individuals.

Respiratory effects of inhaled sulfuric acid on senior asthmatics and nonasthmatics.

The objective of this study was two-fold: (1) to investigate the response of asthmatic subjects who were 60 to 75 y of age to inhaled sulfuric acid, and (2) to compare that response to findings from healthy subjects in the same age group. Nine subjects who had asthma and eight healthy subjects participated. Each subject was exposed to clean air, an inert ammonium sulfate aerosol, or 70 micrograms/m3 sulfuric acid during a 40-min exposure period composed of 30 min at rest and 10 min of light exercise on a treadmill. The sulfuric acid was delivered twice, one preceded by a lemonade drink to neutralize oral concentrations of ammonia. Exposures were separated by at least 1 wk. Oral ammonia levels and pulmonary function parameters (forced expiratory volume in one second, forced vital capacity, and total respiratory resistance) were measured before and after each exposure. None of the functional parameters in either group showed significant changes. However, total respiratory resistance changes from baseline after sulfuric acid exposure were significantly higher (+16%) in the asthmatic subjects, compared with the healthy subjects (-6%). These data suggest that older subjects are not at increased risk for adverse respiratory effects from inhalation of sulfuric acid by virtue of age alone, and older subjects with asthma are slightly more vulnerable than are their healthy peers.

Theophylline mitigates the bronchoconstrictor effects of sulfur dioxide in subjects with asthma.

The objective of the study was to investigate the ability of a sustained-release (SR) theophylline tablet (Uniphyl; Purdue Frederick Co., Norwalk, Conn.) to block or mitigate sulfur dioxide (SO2)-induced bronchoconstriction in adult subjects with asthma. Eight subjects participated in a double-blind, crossover study with a 400 mg theophylline tablet or placebo once a day for a week before a 10-minute SO2 challenge. FEV1 and total respiratory resistance (RT) were measured before and after the SO2 challenge and on a different day before and after an air exposure. After exposure to SO2, average values of FEV1 dropped 16% after placebo treatment and 7% after theophylline treatment. The corresponding percentages for RT were a 37% increase after placebo and a 7% increase after theophylline treatment. Analysis of variance demonstrated a significant difference between the SO2-induced decrease in FEV1 and increase in RT after SR theophylline treatment compared with that of placebo treatment. Thus, we conclude that SR theophylline tablets, taken at this concentration for 1 week, mitigate SO2-induced bronchoconstriction.

Predicting outcome in schizoaffective psychosis.

Predictors of long-term outcome are identified for 68 patients with schizoaffective psychosis from the Chestnut Lodge Follow-up Study. Two dimensions regularly predicted better outcome: better developed premorbid instrumental skills and fewer typically schizophrenic symptoms.

Therapeutic monitoring of theophylline. Rationale and current status.

Theophylline has been demonstrated to be a useful agent in the therapy of chronic asthma. Its use must be tempered with knowledge of its adverse effects and that these effects are related primarily to serum concentration. Accordingly, it is mandatory to monitor serum theophylline concentrations on a regular basis with any patient receiving maintenance therapy with theophylline. It is also necessary to recognise the potential side effects of theophylline therapy, and when such a patient displays symptoms of vomiting, headache or seizures, serum theophylline concentration must be checked even if a recent concentration was within the therapeutic range. The means for monitoring theophylline concentrations are now available even to the average physician who does not have immediate access to a laboratory that can provide timely serum theophylline determinations.

Schizoaffective psychosis. II. Manic, bipolar, and depressive subtypes.

Three schizoaffective subtypes-manic, bipolar, and depressive-were compared across multiple baseline (demographic, premorbid, morbid) and long-term outcome dimensions. Though the subtypes were comparable at baseline, the patients with depressive schizoaffective disorder scored consistently better at follow-up, although none of these differences was statistically significant. Results failed to support the validity of such subtyping in schizoaffective disorder, at least in predominantly chronic populations.

Schizoaffective psychosis. I. Comparative long-term outcome.

Patients from the Chestnut Lodge (Rockville, Md) follow-up study with schizoaffective (SA) psychosis (n = 68) were compared with patients with DSM-III schizophrenia (S, n = 163), bipolar disorder (n = 19), and unipolar disorder (n = 44) on multiple premorbid, morbid, and outcome dimensions. This study required that patients with SA disorder satisfy DSM-III criteria for both S and affective disorder (minus mutual exclusionary criteria). The SA cohort demographic and premorbid profile paralleled that of the cohort with unipolar disorder. At follow-up, however, the profile of SA psychosis paralleled that of S, with no significant differences between these patients on virtually all outcome measures. Results suggest that among samples of long-term inpatient, SA psychosis as defined herein is closer to S than affective disorder.