An experimental study on the regulation of expression of Th2 cytokines from T lymphocytes by protein kinase C in asthma.

Fu J.

Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.

To explore the regulatory role of protein kinase C (PKC) in the expression of Th2 cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5) by T lymphocytes in asthma. T lymphocytes were isolated and purified from blood and bronchial alveolus lavage fluid (BALF) of each guinea pig of normal control group and asthmatic group and from peripheral blood of the asthmatic patients and normal controls, and were stimulated with PKC accelerant phorbol 12-myristate 13-acetate (PMA) and inhibitor Ro31-8220. The expression of IL-4 and IL-5 mRNA and protein was detected by using in situ hybridization staining and ELISA respectively. The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA was significantly higher than that of asthmatic T lymphocytes stimulated without PMA respectively (P < 0.01) and that of normal T lymphocytes stimulated with PMA respectively (P < 0.01). The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA and Ro31-8220 was significantly lower than that of asthmatic T lymphocytes stimulated only with PMA respectively (P < 0.01). It was concluded that PKC might participate in regulating the expression of IL-4 and IL-5 in asthmatic T lymphocytes, and the activation of PKC in T lymphocytes might play an important role in the pathogenesis of asthma.

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Urinary leukotriene E4 and 9 alpha, 11 beta-prostaglandin F concentrations in mild, moderate and severe asthma, and in healthy subjects.

Thompson PJ.

Cooperative Research Centre for Asthma, The University of Western Australia, Perth, Australia.

BACKGROUND: Airway inflammation in asthma is associated with cysteinyl leukotriene and prostaglandin D(2) production. Measurement of urinary metabolites of these eicosanoids may be useful for monitoring asthma patients. However, the influence of asthma phenotype and severity on basal urinary excretion of these metabolites is unknown. OBJECTIVE: To compare urinary leukotriene (LT)E(4) and 9 alpha, 11 beta-prostaglandin (PG)F(2) concentrations in large groups of mild, moderate and severe asthmatic patients and healthy control subjects. METHODS: Asthma severity, treatment and aspirin sensitivity were assessed by questionnaire in 168 asthmatic patients. Basal LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations were measured in urine samples from these patients and from 175 control subjects using enzyme immunoassays. RESULTS: Urinary LTE(4) was correlated with 9 alpha, 11 beta-PGF(2) in both control subjects and asthmatic patients (P<0.002). Median LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations in patients with severe asthma were significantly reduced compared with mild asthmatic patients (P<0.05 and <0.001, respectively). Urinary 9 alpha, 11 beta-PGF(2), but not LTE(4) was lower in asthmatic patients using inhaled corticosteroids (P<0.02). Multiple regression analysis indicated that urinary 9 alpha, 11 beta-PGF(2) concentration was negatively correlated with asthma severity (P=0.003) and also with % predicted FEV(1) (forced expiratory volume in 1 s) (P=0.005). CONCLUSIONS: Baseline urinary LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations are of limited value in discriminating between patients with different severities of asthma. Reduced urinary LTE(4) and 9 alpha, 11 beta-PGF(2) in patients with severe asthma suggest that direct or indirect effects of high-dose corticosteroid therapy combined with other factors associated with severe asthma may influence eicosanoid production. However, the negative association of urinary 9 alpha, 11 beta-PGF(2) with lung function suggests an adverse effect of chronic PGD(2) production on lung function in asthma, irrespective of severity.

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Relationship of outdoor air quality to pediatric asthma exacerbations.

Hornung RW.

Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. michelle.lierl chmcc.org

BACKGROUND: Although exposure to outdoor air pollutants has been shown to be associated with exacerbations of asthma, there are relatively few admissions for asthma to Cincinnati Children's Hospital, Cincinnati, OH during the summer months when air quality tends to be worst. OBJECTIVE: The objective of this study was to determine the relationship of outdoor air quality parameters to asthma exacerbations in children. METHODS: The number of emergency room visits and hospitalizations for asthma were determined by review of emergency department logs and the hospital computer database. Outdoor air concentrations of ozone, particulates of < 10 microm diameter (PM-10), pollens, and fungal spores were obtained from the Hamilton County Department of Environmental Services. Multiple regression analysis was performed, looking for relationships between the daily number of asthma visits and the air quality data for the same day and for 1 through 5 days before the visits. RESULTS: A significant association was found between the number of asthma visits and the daily pollen count (P = 0.014, SE = 0.001). The effect was stronger for visits 1, 2, and 3 days after the pollen count (P < 0.001 for pollen count lagged 3 days). High PM-10 counts were synergistic with the pollen count as a predictor of asthma visits. There was no association between asthma visits and the ozone concentration or fungal spore count. CONCLUSIONS: Exacerbations of asthma severe enough to require visits to the hospital were associated with elevated concentrations of airborne pollens and particulates, with a significant delayed effect. Ozone, in the concentrations measured here, was not a risk factor for severe asthma exacerbations in children.

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Trends and ethnic differences in asthma hospitalization rates in Singapore, 1991 to 1998.

Tan WC.

Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore, Singapore. cofngtp nus.edu.sg

BACKGROUND: A few reports have indicated that asthma hospitalization rates in several countries have stopped rising or started falling in the 1990s. AIM: To describe recent trends and ethnic differences in asthma hospitalization rates in Singapore from 1991 to 1998. METHODS: Asthma hospitalization rates in all hospitals were analyzed by age groups, sex, ethnicity, and individual years, using aggregated data for asthma (ICD-9 493 and ICD-10 J45, J46) from 1991 to 1998, when nationwide data from the Central Claims Processing System were available. RESULTS: Between 1991 and 1998 there were a total of 37,615 hospital admissions for asthma, giving an annual average rate of 17.1 hospital admissions per 10,000 persons. Overall, the rates of asthma hospitalization fell by 28% from 21.7 per 10,000 in 1991 to 15.4 per 10,000 in 1998 (3.5% annually). The trends were broadly based across all age, sex, and ethnic groups. Hospitalizations were more common in boys than in girls aged 0 to 4 (male/female ratio 1.69), but less common in men than women aged 35 to 64 (male/female ratio 0.81). Rates of asthma hospital admissions were higher in Malays (32.8 per 10,000) and Indians (40.8 per 10,000) than Chinese (11.9 per 10,000). CONCLUSIONS: In line with findings from several countries, there have been recent declines in rates of hospital admissions for asthma in Singapore in the 1990s. The declines were broadly based across all population subgroups and parallel previously observed declines in mortality in adults. However, considerable ethnic differences in levels of asthma hospitalization still exist.

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Lower physician estimate of underlying asthma severity leads to undertreatment.

Wu AW.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Suite 7400, 1830 E Monument St, Baltimore, MD 21205, USA. gdiette mail.jhmi.edu

BACKGROUND: Asthma undertreatment has been linked to poor outcomes. National guidelines recommend that physicians classify asthma severity based on pretreatment symptoms and titrate care as the disease changes in the individual patient. This study evaluated the extent to which the physician estimate of underlying severity affects a patient's asthma care. METHODS: Data used were collected from a cohort of adults with asthma enrolled in managed care. Eligible patients were adults enrolled in managed care with medical encounters coded for asthma. Physicians were eligible if they were main asthma providers. The patient survey covered demographics, symptoms, asthma treatment, and self-management knowledge. Physicians were asked to assess the underlying severity of their patients' asthma. RESULTS: There were 4005 patients with asthma with physician estimates of underlying severity. Of the patients, 70.1% were female (mean age, 44.8 years) and 83.5% were white. Most patients' current asthma symptoms were moderate (39.4%) and severe (50.1%). Most physician estimates of underlying severity were mild (44.6%) and moderate (44.5%). Among those patients reporting moderate symptoms, daily inhaled corticosteroid use was reported in 35.2% when physician estimates were mild, 53.0% when moderate, and 68.1% when severe (P =.001). Rates of peak flowmeter ownership, allergy testing, and self-management knowledge tracked similarly with physician estimates of underlying severity. CONCLUSIONS: Physician estimates of underlying asthma severity appear to determine asthma care. For patients with inadequate symptom control, lower physician estimates of underlying severity were associated with care that is less consistent with national guidelines. To improve the quality of asthma care, physicians need to update treatment based on their patients' current symptoms and adapt care accordingly.

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Complexity of terminal airspace geometry assessed by computed tomography in asthma.

Tanizaki Y.

Department of Medicine, Misasa Medical Branch, Okayama University Medical School, Tottori, Japan. fumin cc.okayama-u.ac.jp

Low attenuation areas in computed tomography images from patients with chronic obstructive pulmonary disease have been reported to represent macroscopic and/or microscopic emphysema. The cumulative size distribution of the clusters has been shown to follow a power law characterized by the exponent D, a measure of the complexity of the terminal airspace geometry. We have previously found increased low attenuation areas in nonsmoking subjects with asthma. We examined the size distribution of the clusters in nonsmoking subjects with asthma compared with both nonsmoking control subjects and subjects with asthma with a smoking history. The percentage of lung field occupied by low attenuation areas (LAA%) and D in subjects with asthma with a smoking history differed significantly from nonsmoking subjects with asthma and control subjects. In nonsmoking subjects with asthma, both parameters differed significantly between severe asthma and mild or moderate asthma. The LAA% differed significantly between moderate and mild asthma, but D did not. In mild and moderate asthma, a highly significant correlation between LAA% and D was observed in patients with a smoking history, but not in nonsmoking subjects with asthma. Our results suggest that decreased D is mostly related to emphysematous change, and both measurements of LAA% and D may provide useful information to characterize low attenuation areas in subjects with asthma.

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Discriminant analysis in allergic rhinitis and asthma: methacholine dose-response slope allows a good differentiation between mild asthma and rhinitis.

Olaguibel-Rivera JM.

Department of Allergy, Hospital Virgen del Camino, Pamplona, Spain. jmolaguibel telefonica.net

Asthma and rhinitis frequently coexist in allergic patients, but nasal symptoms may predominate, leading to asthma underdiagnosis and undertreatment. Discriminant analysis obtains the best differentiation between groups using one or one set of variables. Our aim was to identify the laboratory test [allergen exposure, total and specific serum IgE, lung function, blood eosinophils and, bronchial response and sensitivity to methacholine (Mth) and allergen] or combination of them that allowed the best differentiation between mild asthma and allergic rhinitis. A cross-sectional analysis was performed in 86 Dermatophogoides pteronyssinus allergic rhinitis patients, who were classified according to clinical data as rhinitis plus mild asthma (n = 62) or "pure" rhinitis (n = 24). Bronchial symptoms had been exhaustively evaluated during a 2-years pre-inclusion period. Patients underwent skin tests and bronchial challenge with Mth and allergen. The exposure to D. pteronyssinus allergen (Der pl) was quantified in dust samples. Dose-response curves with Mth [until the FEV1 fell by 40% or the maximal dose (200 mg/ml) was inhaled] were attained. We developed multiple models of discriminant analysis in order to evaluate the capacity of the above variables to differentiate groups. Asthma patients had higher total and specific IgE levels and a greater sensitivity (PD20 values) and response [dose-response slope (DRS)] to both Mth and allergen. The model entering these variables was the one that correctly classified more patients (79.2%). The discriminative power of the model that only included Mth-DRS values was similar to the above (78.8%). Bronchial response to Mth is quantitatively different in allergic rhinitis patients who display mild asthma symptoms when compared to those that only report rhinitis, suggesting a distinct bronchial intrinsic behavior. The utilization of complete dose-response curves with Mth allows a good separation between mild asthma and "pure" rhinitis patients and might be useful in the diagnosis of mild asthma. Whether the early detection and treatment of these patients prevents the development of symptomatic asthma needs further evaluation.

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The role of concomitant respiratory diseases on the rate of decline in FEV1 among adult asthmatics.

Barbee R.

Arizona Respiratory Center, The University of Arizona, Tucson, AZ 85724, USA. duane resp-sci.arizona.edu

Several recent reports have presented evidence suggesting that adults with asthma have an accelerated rate of decline in pulmonary function compared with nonasthmatics. However, most of these studies have not taken into account the possible effect of comorbid lung disease in addition to asthma. This study was designed to determine if comorbid respiratory diseases modify or otherwise change the estimates of decline in forced expiratory volume in one second (FEV1). Study subjects were White, non-Mexican, American participants, who were > or = 20 yrs of age at the initial survey and had at least one pulmonary function testing. Respiratory disease status, based on self-reported questionnaires and pulmonary function tests, were assessed during 12 surveys spanning a period of up to 20 yrs. There were 2,926 subjects who met the inclusion criteria, 214 (7.3%) had physician-confirmed asthma, 325 (11.1%) chronic obstructive pulmonary disease (COPD), and 125 (4.3%) both physician-confirmed asthma and COPD. Longitudinal analysis revealed that among those with longstanding asthma, FEV1 values were low but did not decline at a more rapid rate than normal. Likewise, subjects with both asthma and COPD had the lowest levels of FEV1, but also a rate of decline that was not significantly increased. Only those with COPD in the absence of asthma experienced both a low initial FEV1 level and a significantly steeper rate of decline. Based on these findings, the authors conclude that forced expiratory volume in one second does not decline more rapidly in asthmatics or in those with asthma and chronic obstructive pulmonary disease, compared with nonasthmatics.

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