Altered pituitary-adrenal interaction in nocturnal asthma.

Martin RJ.

Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, USA.

BACKGROUND: Increased airway inflammation at night contributes to the nocturnal worsening of asthma, but the mechanisms regulating circadian variations in airway inflammation are unknown. OBJECTIVE: We hypothesized that altered hypothalamic-pituitary-adrenal axis function serves as an endogenous controller of inflammation in nocturnal asthma. METHODS: Patients with nocturnal asthma (n = 7), patients with nonnocturnal asthma (n = 13), and healthy control subjects (n = 11) adhered to a regular sleep-wake cycle for 1 week. Corticotropin and cortisol levels were assayed every 2 hours for 24 hours. Low-dose corticotropin stimulation was performed. Circadian hormonal flux was analyzed by means of cosinor modeling and calculation of the area under the 24-hour curve. RESULTS: Corticotropin peak levels and areas under the 24-hour curve were significantly increased in patients with nocturnal asthma versus values in patients with nonnocturnal asthma and control subjects. Patients with nonnocturnal asthma demonstrated significantly increased areas under the 24-hour cortisol curve when compared with control subjects, but peak cortisol levels did not differ between groups. Cortisol levels after low-dose corticotropin stimulation did not differ between groups. Corticotropin and cortisol levels were not correlated with the degree of physiologic impairment. CONCLUSION: Nocturnal asthma is marked by increased corticotropin levels that are not accompanied by commensurate increases in cortisol levels. This observation might indicate blunted adrenal responsiveness in the nocturnal asthma phenotype. Conversely, adrenal response to corticotropin might be enhanced in nonnocturnal asthma, attenuating nocturnal worsening of airway inflammation.

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US childhood asthma prevalence estimates: the Impact of the 1997 National Health Interview Survey redesign.

Parker J.

Infant and Child Health Studies Branch, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD 20782, USA. lea8 cdc.gov

The 1997 redesign of the National Health Interview Survey (NHIS) affected US childhood asthma prevalence estimates. The 1997 asthma attack prevalence estimate for children 0-17 years was 5.4%. Pre-redesign NHIS childhood asthma period prevalence estimates peaked in 1995 at 7.5%. It is unclear whether the difference reflects the change in survey methodology or changing asthma prevalence. To examine the impact of the NHIS redesign on childhood asthma prevalence estimates, the authors analyzed the 1988 NHIS that contained two sets of asthma questions: the core survey used until 1996 and the Child Health Supplement (CHS) with questions more similar to those in the redesigned 1997 NHIS. The authors measured the difference between 1988 core and CHS childhood asthma prevalence estimates to calculate an inflation factor for 1997-2000 NHIS estimates. The 1988 CHS questions produced asthma prevalence estimates 19-34% lower than the 1988 core question, depending on the methodology used to assess the difference. Inflating the 1997 asthma attack prevalence estimate by these differences yielded modified 1997 estimates ranging from 6.5% (95% confidence interval: 5.6%, 7.5%) to 7.3% (95% confidence interval: 6.4%, 8.2%). The change in the 1997 NHIS asthma questions likely explains much of the difference in asthma prevalence estimates between 1995 and 1997.

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Influences of asthma and household environment on lung function in children and adolescents: the third national health and nutrition examination survey.

Perlin SA.

Office of Research and Development, National Center for Environmental Assessment, Environmental Protection Agency, Research Triangle Park, NC, USA.

The authors examined influences of asthma and household environment (passive smoking, use of a gas stove, and having a dog or cat) on five measures of spirometric lung function among 8- to 16-year-old subjects, as measured cross-sectionally in the Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994). In regression models, independent variables included asthma status, household environmental factors, age, and anthropometric measurements. Regression analyses were weighted by the NHANES III examination sample weighting factor, and results were adjusted for clustering in the sampling design. There were distinct sex differences in the results. In girls, lung function was lowest among active asthmatics taking prescription respiratory medicine, whereas lung function in other active and inactive asthmatics did not differ greatly from that in nonasthmatics. In boys, however, all groups of asthmatics had substantially lower lung function than nonasthmatics. Differences in lung function between active asthmatics and nonasthmatics were stable with increasing age. However, the lung function of inactive asthmatic girls and boys returned to and diverged from nonasthmatics' levels, respectively. In asthmatic girls, passive smoking was associated with reduced lung function; having a dog or cat was associated with increased lung function; and gas stove use was associated with reduced lung function among subjects not taking prescription respiratory medicine.

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The BC Community Pharmacy Asthma Study: A study of clinical, economic and holistic outcomes influenced by an asthma care protocol provided by specially trained community pharmacists in British Columbia.

Waller R.

Pharmaceutical Outcomes Research Unit, Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. wmclean ottawahospital.on.ca

OBJECTIVES: Despite advances in recent years, asthma morbidity and mortality have been noted to be on the increase in the past decade. The present study examined the failures and recommendations of past studies and introduced a new milieu for asthma care--the community pharmacy. The study incorporated a care protocol with the important ingredients of asthma education on medications, triggers, self-monitoring and an asthma plan, with pharmacists taking responsibility for outcomes, assessment of a patient's readiness to change and tailoring education to that readiness, compliance monitoring and physician consultation to achieve asthma prescribing guidelines. METHODS: Thirty-three pharmacists in British Columbia, specially trained and certified in asthma care, agreed to participate in a study in which experienced pharmacists would have asthma patients allocated to enhanced (pharmaceutical) care (EC) or usual care (UC). Pharmacists less experienced were clustered by geography and had their pharmacies randomized to two levels of care; each pharmacy then had patients randomized to EC versus control, UC versus control or EC versus UC depending on their pharmacy randomization. Six hundred thirty-one patients provided consent, of which 225 in EC or UC were analyzed for all outcomes. Patients were followed for one year. RESULTS: Compared with patients in the UC group, the results of those in the EC group were as follows: symptom scores decreased by 50%; peak flow readings increased by 11%; days off work or school were reduced by approximately 0.6 days/month; use of inhaled beta-agonists was reduced by 50%; overall quality of life improved by 19%, and the specific domains of activity limitations, symptoms and emotional function also improved; initial knowledge scores doubled; emergency room visits decreased by 75%; and medical visits decreased by 75%. A patient satisfaction survey revealed that the population was extremely pleased with their pharmacy services. Cost analysis reinforces the EC model, which is more cost effective than UC in terms of most direct and indirect costs in asthma patients. CONCLUSION: Specially trained community pharmacists in Canada, using a pharmaceutical care-based protocol, can produce impressive improvements in clinical, economic and humanistic outcome measures in asthma patients. The health care system needs to produce incentives for such care.

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Increased exhaled 8-isoprostane in childhood asthma.

Montuschi P.

Department of Pediatrics (Drs. Baraldi, Ghiro, Piovan, and Carraro), School of Medicine, University of Padova, Padova, Italy.

STUDY OBJECTIVE: To quantify lung oxidative stress in asthmatic children by measuring concentrations of 8-isoprostane, a marker of oxidative stress, in exhaled breath condensate (EBC), which is a noninvasive method of sampling airway secretions. Secondary objectives were as follows: (1) to measure levels of exhaled prostaglandin (PG) E(2), since impaired PGE(2) production has been implicated in the pathogenesis of asthma in adults; and (2) to measure levels of fractional exhaled nitric oxide (FeNO), which is a marker of airway inflammation. DESIGN: Single-center, cross-sectional study. PATIENTS: Twelve healthy children, 12 steroid-naive asthmatic children, and 30 children in stable condition with mild-to-moderate persistent asthma who were being treated with inhaled corticosteroids (ICSs) [average dose, 300 micro g per day] were studied. INTERVENTIONS: Subjects attended the outpatient clinic on one occasion for the collection of EBC and FeNO measurements. Measurements and results: 8-Isoprostane and PGE(2) concentrations in EBC were measured with specific radioimmunoassays. FeNO was measured online by a chemiluminescence analyzer. 8-Isoprostane was detectable in the EBC of healthy children (mean [+/- SEM], 34.2 +/- 4.5 pg/mL), and its concentrations were increased in both steroid-naive asthmatic children (mean, 56.4 +/- 7.7 pg/mL; p < 0.01) and steroid-treated asthmatic children (mean, 47.2 +/- 2.3 pg/mL; p < 0.05). There was no difference in exhaled 8-isoprostane concentrations between the two groups of asthmatic children (p = 0.14). By contrast, exhaled PGE(2) concentrations were similar among the three study groups (p = 0.56). FeNO levels were higher in steroid-naive children with asthma (49.2 +/- 9.6 parts per billion [ppb]; p < 0.05) and, to a lesser extent, in steroid-treated asthmatic children (37.8 +/- 6.6 ppb; p < 0.05) compared with healthy children (15.2 +/- 1.7 ppb). CONCLUSIONS: Lung oxidative stress is increased in children who are in stable condition with asthma, as reflected by increased exhaled 8-isoprostane concentrations. This increase seems to be relatively resistant to treatment with ICSs. Decreased PGE(2) lung production is unlikely to play a pathophysiologic role in childhood asthma.

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Living with asthma in Sweden--the ALMA study.

Lundback B.

Trosa Health Care Centre, 619 33 Trosa, Sweden. b.stallberg salem.mail.telia.com

BACKGROUND: Recently performed studies have found a number of limitations in the daily lives of asthmatics, and a large disparity between the perception of the sufferers and what health care professionals believe matters to asthmatics. AIM: What matters to Swedish asthma patients, what medicines do they use, and are they compliant with given prescriptions? A further aim was to compare perceptions about asthma and asthma management in asthmatics and among Swedish general practitioners (GP). DESIGN: A structured telephone interview of a representative sample of Swedish asthmatics, and a mailed questionnaire survey among GPs from different parts of Sweden. METHODS: Screening by telephone of a random sample of 10,350 subjects aged 18-45. Of those, 240 were subsequently selected for a detailed structured telephone interview about their asthma. A mailed structured questionnaire containing similar questions to those asked of the asthmatics was sent to 600 GPs, and 139 returned completed answers. RESULTS: 16% of the asthmatics reported (asthma) symptoms occurring every day during the previous month. Nocturnal symptoms at least twice per week were reported by 19%. Both these were reported by considerably higher proportions of the asthmatics than the GPs had expected. A large majority classified their disease as mild or very mild, although great majority reported frequent symptoms. Activities or situations which caused symptoms of asthma often or "now and then" were physical exertion, 67%; bad weather, 59%; contact with animals/pets, 58%; and visits to cafes or restaurants, 36%; and several asthmatics avoided these activities due to their asthma. CONCLUSION: A great majority of asthmatics report a large number of symptoms and limitations in their daily living in proportions which were roughly expected by the GPs.

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Eosinophils from patients with asthma express higher levels of the pan-leucocyte receptor CD45 and the isoform CD45RO.

Walsh GM.

Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen Medical School, Aberdeen, UK.

BACKGROUND: Eosinophils and their secreted mediators are heavily implicated as effector cells in asthma and other allergic diseases. Comparisons were made between expression of CD45, CD45RA, CD45RB and CD45RO by eosinophils from asthmatic patients and non-asthmatic atopic and non-atopic, non-asthmatic control subjects. METHODS: Twenty-seven patients with asthma and 33 control subjects were recruited for the study. Eosinophil expression of CD45, CD45RA, CD45RB and CD45RO was established by immunostaining and flow cytometry was performed on whole leucocyte samples. Eosinophil apoptosis in response to CD45 and CD45 isoform monoclonal antibody (mAb)-dependent receptor ligation was assessed by binding of annexin V and flow cytometry. RESULTS: Eosinophils from patients with asthma expressed significantly (P<0.05) higher levels of pan-CD45 and CD45RO compared with eosinophils from non-asthmatic, non-atopic subjects. No significant correlations were found between expression of either pan-CD45 or CD45RO and the degree of symptoms in the asthmatic patients as defined by lung function (FEV1 and FEF25-75) and methacholine PD20. Increased expression of pan-CD45 or CD45RO did not appear to be a consequence of the atopic phenotype. Higher expression of pan-CD45 or CD45RO by eosinophils from asthmatic patients was not associated with greater sensitivity to CD45 and CD45RO mAb receptor ligation-induced eosinophil apoptosis. CONCLUSION: Higher expression of CD45 and CD45RO by eosinophils from asthmatic patients appeared to be a consequence of asthma rather than atopy and further supports a role for activated eosinophils in asthma.

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Effectiveness of Acute Asthma Care Among Inner-city Adults.

Khan DA.

Division of General Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 75390-9103, USA. yvonne.coyle utsouthwestern.edu

BACKGROUND: Acute asthma often requires expensive emergency department visits and hospitalizations, especially among economically disadvantaged inner-city adults. However, few studies have examined approaches for improving acute asthma care in this population. METHODS: We conducted a cohort study involving patients who were discharged from a public hospital emergency department following acute asthma care between March 31, 1997, and August 5, 1999, to identify processes of care effective for improving peak expiratory flow rate at a 2- to 3-week follow-up. Adult patients who met the predetermined criteria for asthma, who underwent a baseline peak expiratory flow rate reading, and who did not have concurrent acute sinusitis or pneumonia were eligible (N = 448). Of the 365 patients enrolled in the study, 309 (84.7%) completed it. We used a multiple linear regression analysis adjusted for patient risk to assess the association between acute asthma care processes derived from the National Asthma Education Prevention Program guidelines (inhaled beta2-agonists, inhaled corticosteroids, systemic corticosteroids, asthma care follow-up, and patient asthma education) and percentage peak expiratory flow rate change at follow-up. RESULTS: Systemic corticosteroids had a significant effect for increasing percentage peak expiratory flow rate change at the 2- to 3-week follow-up for all asthma exacerbation severity levels (beta = 26.1; 95% confidence interval, 1.8-50.5; P =.04) and severity levels specified by the National Asthma Education Prevention Program guidelines (beta = 31.6; 95% confidence interval, 8.1-55.1; P =.01). CONCLUSION: Outpatient systemic corticosteroids were effective for improving lung function 2 to 3 weeks after acute asthma care, and their use should reduce asthma-related morbidity, especially among economically disadvantaged inner-city adults.

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