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PubMed2002

Effects of asthma and asthma therapies on bone mineral density.

With improvements in techniques for measuring bone mass, interest and concern have increased about the effects of asthma therapies, particularly corticosteroids, on bone mineral density. Whether asthma itself causes bone loss remains unclear. Studies evaluating the effect of asthma therapies on bone mineral density are often difficult to interpret because of methodologic problems. These studies show that oral corticosteroids are associated with a reduction in bone mineral density and an increased risk of fracture. Studies evaluating the effects of inhaled corticosteroids on bone mineral density provide conflicting data, but there is increasing evidence that inhaled corticosteroids may have an adverse effect on bone. However, the benefits of inhaled corticosteroids in the treatment of asthma remain far greater than the risks. The data for the effects of other asthma therapies on bone mineral density are limited.

Asthma↗
PubMed2005

Effects of nursing instruction on asthma knowledge and quality of life in schoolchildren with asthma.

The issue of whether nursing instruction efforts could improve asthma knowledge and quality of life among schoolchildren was investigated using a quasi-experimental design. The key instruments were the Asthmatic Knowledge Questionnaire and the Childhood Asthma Questionnaire-Form B. Asthmatic knowledge increased among children who received instruction from nurses (Meanpre/post=22.20/31.87, p<.05). These children also experienced significant improvements in their active quality of life (Meanpre/post=27.53/30.20, p<.05), and decreased distress (Meanpre/post=24.04/10.86, p<.05) and asthma severity (Meanpre/post=13.27/8.3, p<.05). This study finds nursing instruction helpful in improving asthma knowledge. However, in terms of quality of life, elevated knowledge has a marked (negative) correlation only with levels of distress and severity. It shows no detectable relationship with active or passive life quality. Therefore, though nursing instruction can improve schoolchildren's knowledge about asthma, the improvement in knowledge only relates to reducing distress and severity and thus improving quality of life. This result can provide guidance for nursing personnel in developing nursing instruction to improve active quality of life in child patients.

Ambulatory Care↗
PubMed2004

Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma, and their relationships to airway hypersensitivity or maximal airway response to methacholine.

BACKGROUND: The aims of this study were to compare the degree of airway inflammation in cough-variant asthma (CVA) with that in classic asthma (CA), and to examine the relationship between airway inflammation and airway hypersensitivity or maximal airway response to methacholine in both conditions. METHODS: Sputum was induced in 41 CVA patients, in 41 methacholine PC(20)-matched CA patients, and in 20 healthy children. The sputum samples were analyzed for total and differential cell counts, and for eosinophilic cationic protein (ECP). A high-dose methacholine challenge test was performed in CVA and CA patients to determine PC(20) and maximal airway response. RESULTS: Sputum eosinophil percentages and ECP levels were significantly elevated in CVA and CA vs the control, but no significant differences were found between the two asthma groups. In the two asthma groups, neither sputum parameters correlated significantly with methacholine PC(20). However, the absence of a maximal response plateau or its higher level, when present, was associated with increased eosinophil percentages and ECP levels in the CVA group. CONCLUSIONS: The degree of eosinophilic inflammation may not be causally related to differences in presented asthma manifestations. The identification of a maximal response plateau and the level of this plateau in patients with CVA may provide information pertinent to airway eosinophilic inflammation.

Adolescent↗
PubMed2005

Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. METHODS: After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy. RESULTS: Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis. CONCLUSION: Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.

Administration, Inhalation↗
PubMed2005

The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma.

BACKGROUND: Endotoxin, with its potential to enhance type 1 immunity, is a significant player in the hygiene hypothesis. The combined effects of the genetic variants of various molecules in the endotoxin response pathway on asthma related phenotypes are largely unknown. OBJECTIVE: To investigate the effects of the genetic variants of CD14 and TLR4 genes on asthma phenotypes in a large number of asthmatic children. METHODS: 613 asthmatic children were genotyped at the CD14-C159T, TLR4-A896G and TLR4-C1196T loci. IgE, eosinophil numbers and FEV1 were compared in 327 children who were not on any controller medications and were symptom free. Multivariate logistic regression was used to determine the factors associated with total IgE. RESULTS: Among children with atopic asthma, total IgE levels were significantly different among the three genotypes in the co-dominant model [CC: 435 kU/l (interquartile range: 146-820); CT: 361 (140-710); TT 204 (98-435), P = 0.035]. TT genotype was significantly and independently associated with lower IgE levels (OR: 0.5 95%; CI = 0.28-0.90, P = 0.021). Both TLR4-A896G and TLR4-C1196T polymorphisms were more frequent in the mild asthma group with atopy (P = 0.032, 0.018, respectively). The combined effects of the genetic variants in CD14 and TLR4 genes did not improve the observed associations. CONCLUSION: Our study demonstrates that the CD14-C159T promoter variant influences total IgE levels and also indicates that the T allele has a more profound effect on total IgE in children with atopic asthma. Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the population studied.

Adolescent↗
PubMed2005

Influence of an asthma education program on parents with children suffering from asthma.

Several studies have evaluated the effectiveness of various methods of asthma education for parents. This study adds a qualitative and inner perspective from the families of children suffering from asthma. The aim was to illuminate the influence of an asthma education program (AEP) for parents. The study sample consisted of nine parents of five children with moderate to severe asthma in the 2-6 years age group. Data were collected by interviews and qualitative analyses were used. The main findings were that the parents experienced an increased understanding of their child's experience of asthma after having participated in the program. Three themes were revealed: sharing experiences, accepting the illness, and partnership building. In conclusion, the parents in the study expressed that they promote increased self-understanding by meeting other parents in groups.

Asthma↗
PubMed1997

The free-running asthma screening test: an approach to screening for exercise-induced asthma in rural Alabama.

This study documented the prevalence of exercise-induced asthma (bronchospasm) in rural elementary schools and described the use of a free-running asthma screening test (exercise-challenge) and peak expiratory flow rate measurements for screening in a school setting. Of 437 children screened, 25 (5.72%) had a > or = 15% decrease in post-exercise peak expiratory flow rate which is indicative of exercise-induced asthma. Absenteeism and poverty were associated with findings of exercise-induced asthma. Early detection of exercise-induced asthma in school-age children through screening would facilitate early treatment, enhance exercise-related activities, and decreases school absences.

Absenteeism↗
PubMed2006

Partners in school asthma management: evaluation of a self-management program for children with asthma.

The "Partners in School Asthma Management" program for inner-city elementary school children comprises (1) case finding; (2) linkage of school nurses, parents, and clinicians; (3) a computer-based tailored educational program; and (4) school environmental assessment and intervention. Case finding identified 1730 children in 60 elementary schools with probable asthma; 835 (96% Hispanic or African American) joined the study. Baseline, posttest, and follow-up measures of asthma knowledge, self-efficacy, and self-management behavior were obtained from the children, and data on symptoms, emergency department visits, and hospitalizations were obtained from their parents. The schools provided data on grades and absences. Each school had a baseline and follow-up environmental assessment. The children in the intervention group showed greater increases in knowledge, self-efficacy, and some aspects of self-management. No differences between groups were found in health status variables, school performance, attendance, or levels of environmental allergens in schools. In 15 schools, an enhanced intervention allowed children and their parents to meet with a project physician, develop an asthma action plan, and receive a 1-month supply of medication; the project physician then followed up with the child's community physician. Children participating in this enhanced intervention had better school performance and fewer absences than the comparison group. Overall, the program was effective in improving children's asthma self-management but not in improving their health status. While the case-finding, computer-based self-management training program and linkage system were successfully implemented, the program failed in creating needed changes in the medical (action plans by community physicians) and physical environments (reduced school allergen levels) of the children.

Absenteeism↗
PubMed1993

Steroid prescribing for asthmatics: relationship with Asthma Symptom Checklist and Living with Asthma Questionnaire.

Psychosocial consequences of asthma were assessed for 42 patients attending an out-patient clinic using the Asthma Symptom Checklist (ASC), a five-dimensional scale of experience during asthma attacks, and the Living with Asthma Questionnaire (LWAQ), a unidimensional scale of experience between attacks. Although all subscales of the ASC and the LWAQ correlated with the physician's prescription of steroids, multiple regression showed that 32 per cent of the prescription decision variance was accounted for by two dimensions of the ASC, panic-fear and irritability. The LWAQ did not explain additional prescription variance, indicating that the physician's decisions were influenced by psychological reactions during asthma attacks rather than between attacks. Prescription decisions were not influenced by clinic-measured respiratory function. The results show some differences with previous studies; implications for patient management are discussed.

Adaptation, Psychological↗
PubMed1988

Asthma deaths in England and Wales 1931-85: evidence for a true increase in asthma mortality.

A recent increase in asthma mortality has been reported in several countries. Such increases can be brought about by changes in factors acting close to the time of death, but they may also be caused by risk factors determined by the generation into which a person is born, as indicated by the year of birth. Asthma mortality rates since 1931 are independently associated with birthdate as well as date of death. In particular there has been an increase in asthma mortality in birth cohorts born since the 1940s. Such changes are unlikely to be due to a change in reporting of asthma deaths, and other evidence including the reported increase in the prevalence of eczema in succeeding National Birth cohorts supports the view that these changes may be due to an increased prevalence of atopy. In the absence of any further improvements in the management of asthma, such an increased prevalence of atopy implies that the mortality rate is unlikely to decline substantially for some years to come.

Adolescent↗
PubMed1988

Asthma in the army: a retrospective study and review of the natural history of asthma and its implications for recruitment.

In an attempt to define the problem of asthma in the British Army and to relate it to recruiting policy, records were obtained for all discharges from the Army and all admissions to hospital for 48 hours or more with a principle diagnosis of asthma over four years. There were approximately 50 medical discharges from asthma per year, representing about 1 in 3400 of the held strength of the Army and 6.3% of the discharges from all medical causes. The average number of non-effective days before discharge was about 20 and those discharged were generally young (57% aged 20 years or less), of short service (47% less than 2 years service) and of low rank (86% privates, apprentices or juniors). Three hundred and fifty two individuals were admitted to hospital on 415 occasions in 4 years, of whom 82 were eventually discharged from the service for medical reasons. Average non-effective days for this group was 11. There was only one death. Of 108 discharged soldiers who were eventually shown to have a history of asthma in childhood (HAC), this was identified at recruit examination in only 43%. Before enlistment, only 20% were referred for consultant opinion and only 6% had exercise testing. 28% were probably current asthmatics on entry. From available records, age of remission of childhood asthma was most commonly 10-14 years (64%). Relapse was commonest at age 17-21 years (76%) with 25% of relapses occurring at 18 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Relation of measures of asthma severity and response to treatment to outcome in acute severe asthma.

BACKGROUND: It would be helpful if patients with asthma who require admission to hospital for an acute attack could be identified. METHODS: The relation between the severity of an attack of asthma as determined by admission assessment and the eventual outcome was studied in 52 asthmatic patients aged 14 to 44 years and admitted to an asthma emergency room. The patient's history, including medication and previous admissions to hospital, was recorded and a clinical assessment, including a full inspiratory and expiratory flow-volume loop, was performed on four occasions: on admission, at two hours and at 12-18 hours after the start of a standardised treatment, and two weeks later on an outpatient basis. Patients who were discharged and who had an uneventful follow up at the two week assessment were defined as good responders. Patients who had to be admitted to hospital after 12 to 18 hours or were readmitted during the two weeks, or both, were defined as poor responders. RESULTS: Thirty eight patients were good responders and 14 were poor responders (seven admitted at 12 to 18 hours, seven returned to hospital). All four patients with a raised arterial carbon dioxide tension (PaCO2) (> or = 6 kPa) and the three with cyanosis were in the poor responder group, and this group had lower peak expiratory flow (PEF) values (21% v 30% predicted) on admission. There was, however, considerable overlap in PEF between the two groups and no clinical measure was able to distinguish between the good and the poor responders reliably. Poor responders had a history of more chronic systemic steroid administration, regular use of inhaled beta agonists, and asthma related hospital admissions. Nearly all the subjects showing a good response to standardised treatment had a PEF > 75% predicted and an FEV1 > 65% predicted 12 to 18 hours after the start of treatment. CONCLUSION: Prediction of outcome at admission was not possible in individual patients. A history of poor long term control of asthma, a PEF < 30% of predicted, a PaCO2 > or = 6 kPa, the presence of cyanosis, and lack of early response to treatment indicated a group of asthmatic patients who are less likely to respond to conventional emergency treatment over a short period.

Acute Disease↗
PubMed1993

Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness.

BACKGROUND: Bronchial mucosal inflammation and epithelial damage are characteristic features of asthma. Activation of T helper lymphocytes may contribute to this process by mechanisms including the release of cytokines promoting eosinophil infiltration and activation. METHODS: Bronchial washings and bronchoalveolar lavage fluid were obtained from 29 atopic asthmatic patients (19 with current symptoms and 10 symptom free) and 13 normal volunteers. Flow cytometry was used to assess T cell phenotype and activation status in bronchoalveolar lavage fluid and peripheral blood, and differential cell counts were made on bronchial washings and bronchoalveolar lavage fluid. Findings were related to severity of disease as reflected by symptom scores, baseline lung function, and airway responsiveness. RESULTS: CD4 T lymphocytes in bronchoalveolar lavage fluid and blood from asthmatic patients were activated by comparison with controls (CD4 CD25, median 16.8% v 8.7% for bronchoalveolar lavage fluid, and 15.3% v 8.7% in blood). Bronchoalveolar lavage fluid CD4 T cells from both asthmatic patients and controls were of memory phenotype (95.8% and 96.8% CD45RO and 1.7% and 0.4% CD45RA respectively), whereas both CD45RO and CD45RA T cells were present in blood. Patients with asthma and current symptoms showed increased bronchoalveolar T cell activation compared with patients without symptoms (CD4 CD25 18.7% v 12.3%). Within the asthmatic group there was a significant association between CD4 CD25 lymphocytes and asthma symptom scores (rs = 0.75), airway methacholine responsiveness (log PC20, rs = -0.43) and baseline FEV1 (rs = -0.39). A correlation was also found between CD4 CD25 lymphocytes and eosinophils in bronchoalveolar lavage fluid (rs = 0.48). Eosinophils in bronchoalveolar lavage fluid were increased in asthmatic patients compared with controls and the percentage of eosinophils in bronchoalveolar lavage fluid correlated with asthma symptom score. A relation was found between percentage of epithelial cells in bronchoalveolar lavage fluid and FEV1 and methacholine PC20. CONCLUSION: These results support the hypothesis that selective activation of memory CD4 T cells contributes to eosinophil accumulation, bronchial hyperresponsiveness, and symptoms in asthma.

Adult↗
PubMed1997

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Administration, Inhalation↗
PubMed1997

An evaluation of colchicine as an alternative to inhaled corticosteriods in moderate asthma. National Heart, Lung, and Blood Institute's Asthma Clinical Research Network.

Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 microg daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomized to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81+/-1.38 versus 2.11+/-2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.

Administration, Inhalation↗
PubMed2000

Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFN-gamma-producing CD8(+) T cells in asthma.

Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-gamma were detected in T cells and CD8(+) T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-gamma. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-gamma was found, which was related to an increased capacity of CD8(+) T cells to produce IFN-gamma. The number of IFN-gamma-producing CD8(+) T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-gamma-producing CD8(+) T cells in the blood, possibly controlled by IL-12.

Adult↗
PubMed1977

Fate of occupational asthma. A follow-up study of patients with occupational asthma due to Western Red Cedar (Thuja plicata).

Thirty-eight patients with red cedar asthma proved by inhalation provocation test were studied after they had left exposure for more than 6 months. Twenty-seven patients became asymptomatic, with normal lung function (group A). Three patients had persistent chronic bronchitis with a moderate degree of airway obstruction, probably as a result of cigarette smoking (group B1). Eight patients continued to have recurrent attacks of asthma that decreased in severity after cessation of exposure, and their symptoms were probably due to previous exposure (group B2). The effect of breathing helium on maximal expiratory flow at 50 per cent of the vital capacity was studied. All except one patient in group A were responders (change in maximal expiratory flow at 50 per cent of vital capacity greater than 30 per cent). Two patients in group B1 and 2 in group B2 were nonresponders, suggesting obstruction in the small airways. All patients with red cedar asthma demonstrated bronchial hyperreactivity to methacholine to the same extent as patients with nonoccupational asthma. This hyperreactivity persisted after they left exposure, irrespective of symptoms. It is not known at present whether bronchial hyperreactivity is the predisposing factor in occupational asthma or is the result of the disease.

Adult↗
PubMed2004

Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.

Adrenal Cortex Hormones↗