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PubMed2004

The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network.

Pediatric asthma remains an important public health concern as its prevalence and cost to the health care system is rising. In order to promote innovative research in asthma therapies, the National Heart, Lung and Blood Institute created the Childhood Asthma Research and Education Network in 1999. As its first study, the steering committee of the Childhood Asthma Research and Education Network designed a randomized clinical trial to determine if persistent asthma could be prevented in children at a high risk to develop the disease. This communication presents the design of its first clinical trial, the Prevention of Asthma in Kids (PEAK) trial and the organization of the Childhood Asthma Research and Education Network that developed and implemented this trial. Studies of the natural history of asthma have shown that, in persistent asthma, the initial asthma-like symptoms and loss of lung function occur predominately during the first years of life. Therefore, in the Prevention of Asthma in Kids study, children 2 and 3 years old with a positive asthma predictive index were randomized to twice daily treatment with fluticasone 88 microg or placebo via metered-dose inhaler and Aerochamber for 2 years. The double blind treatment period was followed by a 1-year observational period. Lung function was measured by spirometry and oscillometry technique at 4-month intervals throughout the study. Bronchodilator reversibility and exhaled nitric oxide (ENO) studies were performed at the end of the treatment and observation periods. The primary outcome measure was the number of asthma-free days. Other secondary outcomes included number of exacerbations, use of asthma medications and lung function. These measures were chosen to reflect the progression of the disease from intermittent wheezing to persistent asthma and measurement of the extent of airflow limitation and airway reactivity.

Administration, Inhalation↗
PubMed2003

Hospitalization for asthma: atopic, pulmonary function, and psychological correlates among participants in the Childhood Asthma Management Program.

BACKGROUND: Asthma in childhood has a significant impact on children and families, in part because of the frequent need for hospital-based care for acute exacerbations. Sensitization and exposure to inhalant allergens have been identified as risk factors for asthma hospitalization. OBJECTIVE: The Childhood Asthma Management Program (CAMP), comprised of 1041 children aged 5 to 12 with mild-to-moderate asthma, provides the opportunity to identify specific risk factors for prior hospitalization for asthma. METHODS: Data gathered during the screening period from CAMP were evaluated to elucidate differences between patients who had ever been hospitalized for asthma before enrollment in CAMP and those who had never been hospitalized. RESULTS: Univariate analyses indicated that prior hospitalization for asthma was associated with a younger age of asthma onset, longer duration of asthma, greater number of positive allergy skin tests, higher serum immunoglobulin E level, greater peripheral blood eosinophilia, greater recent inhaled corticosteroid use, greater airflow obstruction, greater airway hyperresponsiveness, and lower patient intelligence quotient (IQ). Gender, race, and family income did not differ between hospitalized and never-hospitalized patients. The combination of both sensitization and exposure to high levels of dog allergen (Can f1) was associated with greater likelihood of prior hospitalization. Forward multivariate logistic regression analysis identified younger age of asthma onset, longer duration of asthma, recent use of asthma controller therapy, greater airflow obstruction, and lower patient IQ as significant risk factors for prior hospitalization when all risk factors identified by univariate analysis were included in the model. CONCLUSIONS: Children with mild-to-moderate asthma who had a past hospitalization for acute asthma had greater asthma severity, younger age of onset, and lower patient IQ at the time of entry into CAMP. They also had more markers of atopy than children without prior hospitalization, although atopy was not associated with prior hospitalization on multivariate analysis. Although we have identified these risk factors in a retrospective manner, one can speculate that the persistence of these features should alert the clinician to closely follow abnormalities on pulmonary function tests and general features of atopy to potentially identify patients at risk for future hospitalization.

Age of Onset↗
PubMed1991

Facilitated referral to asthma specialist reduces relapses in asthma emergency room visits.

Facilitated asthma-specialist care delivered by allergists was compared to generalist care on the rate of relapse of asthma emergency room (ER) visits and hospitalizations and on asthma control in a prospective, controlled study of San Diego Kaiser Health Plan members with asthma. Subjects with asthma between the ages of 6 and 59 years presenting for acute ER care for asthma were systematically assigned by alternating, consecutively, the day of their ER visit to receive either (1) facilitated referral to an asthma specialist within the allergy department and concomitant comprehensive ongoing asthma care (intervention group, n = 149) or (2) continued outpatient management from generalist physicians (control group, n = 160). The course of their asthma was evaluated blindly during the subsequent 6 months by review of medical records, initial and follow-up questionnaires, and spirometry. Compared to the control group, the intervention group noted (1) a 75% reduction in the number of, and percent of, subjects with asthma awakenings per night (p less than or equal to 0.0001), (2) an almost 50% reduction in asthma ER relapses (p = 0.017) resulting from a reduction in the frequency of multiple relapse (p = 0.005), and (3) a greater use of inhaled corticosteroids (p less than 0.00001) and cromolyn (p = 0.002). Thus, facilitated referral of subjects with asthma to specialists in asthma therapy after acute ER therapy appears to reduce asthma ER relapses and to improve asthma outcome.

Adult↗
PubMed2006

Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists.

BACKGROUND: The development of the Asthma Control Test (ACT), a short, simple, patient-based tool for identifying patients with poorly controlled asthma, was recently described in patients under the routine care of an asthma specialist. OBJECTIVES: We sought to evaluate the reliability and validity of the ACT in a longitudinal study of asthmatic patients new to the care of an asthma specialist. METHODS: Patients (n=313) completed the ACT and the Asthma Control Questionnaire (ACQ) at 2 physician visits (4-12 weeks apart). Pulmonary function was measured, and asthma specialists rated asthma control. RESULTS: Internal consistency reliability of the ACT was 0.85 (baseline) and 0.79 (follow-up). Test-retest reliability was 0.77. Criterion validity was demonstrated by significant correlations between baseline ACT scores and baseline specialists' ratings of asthma control (r=0.52, P<.001) and ACQ scores (r=-0.89, P<.001). Discriminant validity was demonstrated, with significant (P<.001) differences in mean ACT scores across patients differing in asthma control, pulmonary function, and treatment recommendation. Responsiveness of the ACT to changes in asthma control and lung function was demonstrated with significant correlations between changes in ACT scores and changes in specialists' ratings (r=0.44, P<.001), ACQ scores (r=-0.69, P<.001), and percent predicted FEV1 values (r=0.29, P<.001). An ACT score of 19 or less provided optimum balance of sensitivity (71%) and specificity (71%) for detecting uncontrolled asthma. CONCLUSIONS: The ACT is reliable, valid, and responsive to changes in asthma control over time in patients new to the care of asthma specialists. A cutoff score of 19 or less identifies patients with poorly controlled asthma. CLINICAL IMPLICATIONS: In a clinical setting the ACT should be a useful tool to help physicians identify patients with uncontrolled asthma and facilitate their ability to follow patients' progress with treatment.

Adolescent↗
PubMed2005

Higher BMI is associated with worse asthma control and quality of life but not asthma severity.

Asthma and obesity tend to co-occur, but relatively few studies have linked obesity, measured using body mass index (BMI), to clinically relevant measures of asthma morbidity. This study assessed BMI in a Canadian sample of asthma outpatients, and evaluated associations between BMI and levels of asthma severity, asthma control, and asthma-related quality of life. A total of 382 adult asthma patients underwent demographic and medical history interviews on the day of their clinic visit. Patients' self-reported height and weight were used to calculate BMI (kg/m(2)). Asthma severity was classified according the GINA (2002) guidelines. Patients completed the Asthma Control (ACQ) and Asthma Quality of Life (AQLQ) Questionnaires and underwent standard pulmonary testing (spirometry). A total of 139 (36%) patients had a normal BMI; 149 (39%) patients were overweight; and 94 (25%) patients were obese. There was no relationship between BMI and asthma severity when controlling for age and sex. Patients with higher BMI scores had higher ACQ and lower AQLQ scores, independent of age, sex and asthma severity. Results identify higher BMI and obesity as potential behavioral factors related to worse asthma control and quality of life, but not asthma severity, and suggest important avenues for asthma management and control initiatives.

Adult↗
PubMed1998

Difficult-to-control asthma: clinical characteristics of steroid-insensitive asthma.

BACKGROUND: Although widely used, little is known regarding the patterns of response that subjects with severe asthma exhibit to oral glucocorticoid (GC) therapy. METHODS: We retrospectively reviewed the charts of 164 consecutive adolescents admitted to the National Jewish Medical and Research Center for difficult-to-control asthma. Data collected included medical history, pulmonary function measures by plethysmography, methacholine challenge results, AM cortisol levels, serum IgE, total eosinophil counts (TEC), serum eosinophil cationic protein (ECP), soluble IL-2 receptor (sIL-2R), and spirometry. RESULTS: Eighty-seven patients (53%) required a GC burst during the hospitalization secondary to poor asthma control. Those requiring a GC burst had a significantly longer history of asthma, a greater degree of bronchial hyperresponsiveness, and lower pulmonary function. Twenty-one patients (24%) failed to respond with a greater than 15% improvement in their AM prebronchodilator FEV1 after the GC burst and were termed steroid insensitive (SI). Although those with SI asthma had a similar duration of asthma, they required oral GC therapy at a younger age, required a larger maintenance oral GC dose on admission, and were more likely to be African-American, compared with those with steroid-sensitive asthma. Furthermore, two distinct spirometry patterns were noted among the SI asthmatic subjects: "chaotic" and "nonchaotic." Patients with the chaotic pattern were characterized by a significant degree of variability (greater than 30%) in daily pulmonary function, whereas those with nonchaotic, SI asthma were characterized by less than 15% variability in daily lung function. Those with nonchaotic SI were diagnosed with asthma and treated with oral GCs at a later age. CONCLUSIONS: This retrospective study suggests that SI asthma is quite common (25%) among adolescents with severe asthma evaluated at a national referral center. In addition, two distinct patterns of SI asthma have been identified that may constitute different pathophysiologic processes. Finally, the overrepresentation of African-Americans in the SI group supports the need for further epidemiologic studies investigating the prevalence of SI asthma and the impact early asthma intervention may have on this severe form of asthma.

Adolescent↗
PubMed2001

The relationships between patients' related variables in asthma: iplications for asthma management.

OBJECTIVE: Understanding patients' personal characteristics is essential for better asthma management. This study assessed the relationships between patients' related variables in asthma and identified key associations relevant to asthma management. METHODOLOGY: Subjects were recruited from the Alfred Hospital Asthma and Allergy Clinic (Melbourne, Victoria, Australia) and general practices. Their clinical and demographic characteristics, asthma knowledge, impact of asthma on their quality of life, their self-management skills and attitudes to asthma were assessed. RESULTS: One hundred and sixty-nine subjects participated in the study. Fifty-seven per cent had one or more previous hospital admissions, 94% had either moderate or severe asthma, and 51% reported nocturnal symptoms in the last 6 weeks. Patients who spoke only English, had been admitted to an intensive care unit, had a peak flow meter, and an asthma action plan had significantly better asthma knowledge than those who did not. The impact of asthma was greatest in patients who had a peak flow meter, used oral steroids, had exercise limitation, and developed asthma between the ages of 31-45 years. Female patients had better self-management skills than males. Patients with asthma-related distress were more likely to use oral steroids or theophylline and to have a history of previous hospital admissions. Patient self-confidence was negatively correlated with age. CONCLUSIONS: There are significant relationships between many of patients' variables related to asthma, including their personal clinical, demographic and psychological characteristics. The findings have implications for optimizing asthma management.

Activities of Daily Living↗
PubMed1996

The asthma year in Swedish pharmacies: a nationwide information and pharmaceutical care program for patients with asthma.

OBJECTIVE: To increase the understanding of asthma among patients and the general public in Sweden and to increase the collaboration among healthcare personnel for the benefit of asthma patients. DESIGN: Based on the results from problem detection studies, Apoteksbolaget, the national organization for pharmacies in Sweden, designed a program to educate healthcare professionals and the public about asthma. Entitled the "Asthma Year," all pharmacy staffs were offered education on asthma, patients were provided written information and audiovisual materials, and the general public was made more aware of asthma through local media. SETTING: Pharmacies, healthcare centers, hospital outpatient areas, libraries, places of work, and domestic airports. PARTICIPANTS: All pharmacy staffs (12,000 persons) were offered an education on asthma. Patients with asthma were offered brochures and leaflets in pharmacies and information in the pharmacy magazine Apoteket. The general public received information about asthma through posters, radio, and television. MAIN OUTCOME MEASURES: The evaluations of the Asthma Year indicate that the activities had an impact on the public, on patients with asthma, and on the pharmacy staffs. RESULTS: About 4.5 million people in Sweden (42% of the population) observed the Asthma Year or received information about asthma, and 49% of the patients learned something new about their disease. Twice as many patients used steroid therapy regularly after the campaign than before. Of the pharmacy staffs, 96% were favorable to the idea of working with campaign years and 85% believed that they were personally involved with the activities. CONCLUSIONS: Patient outcomes in terms of reduced morbidity have not been possible to document, but the number of deaths from asthma in Sweden decreased from 438 during the previous year to 398 during the Asthma Year.

Adolescent↗
PubMed2002

Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids.

BACKGROUND: Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP). STUDY OBJECTIVE: s: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels. DESIGN: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy. PATIENTS: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 micro g bid, or placebo. RESULTS: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma. CONCLUSIONS: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.

Administration, Inhalation↗
PubMed1996

Improving the treatment of nocturnal asthma: use of an office questionnaire to identify nocturnal asthma symptoms.

Nocturnal asthma is a major problem in many asthma patients and it is important to recognize and treat it. We previously reported the incidence of nocturnal asthma in our practice (1); the current study was done to try to improve upon the incidence of nocturnal asthma in our patients. After our previous survey, which indicated a 67% incidence of nocturnal asthma in our practice, we instituted a previsit questionnaire regarding nocturnal asthma to be filled out by all follow-up asthma patients in our office. After a period of time, we mailed a nocturnal asthma questionnaire to all asthma patients to see if the intervention had improved our incidence of nocturnal asthma. This questionnaire was identical to the one used in our prior study and was mailed to 2019 patients. We had 602 responders, 560 of whom had asthma. A total of 328 of these patients (59%) had nocturnal asthma. This was similar to the results of our previous survey, and our initial conclusion was that the new in-office questionnaire that we instituted had not improved the situation. Then we discovered that the in-office questionnaire had inadvertently been distributed only to the patients of one or our physicians (Dr. A). His patients were then compared with those of the other two doctors (Drs. B and C), and it was found that Dr. A's patients had fewer nocturnal symptoms than did the patients of the other doctors. The percent of asthmatics with nocturnal asthma 4-7 nights per week (more than half the nights in a week) for Dr. A was 16%, for Dr. B 47%, and for Dr. C 39%. The use of a short office questinnaire for asthma patients before they see the doctor for follow-up visits leads to greater recognition and better treatment of nocturnal asthma.

Asthma↗
PubMed2001

Impact of a targeted asthma intervention program on treatment costs in patients with asthma.

OBJECTIVE: To evaluate the impact of a targeted asthma intervention on treatment costs, utilization of medical services, number of prescription drugs filled, and trends of medication use from a third-party perspective. STUDY DESIGN: Longitudinal population-based study. METHODS: Study asthmatic patients were classified into intermittent and persistent asthma groups according to the Health Plan Employer Data and Information Set (HEDIS) 2000 asthma measurement. The intervention instituted appropriate asthma drug therapy according to National Heart, Lung, and Blood Institute guidelines. A paired t test and analysis of covariance were used to compare treatment costs and the number of prescriptions dispensed in the 9 months before and the 9 months after the intervention. RESULTS: The study patients (n = 1616) included 566 with intermittent asthma and 1050 with persistent asthma. After the intervention, treatment costs per patient increased significantly by $122 in the intermittent asthma group (P = .001) but decreased significantly by $247 in the persistent asthma group (P < .001). Costs incurred by patients with persistent asthma decreased by $149 for hospitalization (P = .003), $16 for emergency room visits (P < .001), $82 for physician visits (P < .001), and increased by $1 for asthma medications (P = .938). The number of asthma medication prescriptions per patient increased by 0.72 prescriptions in the intermittent asthma group (P < .001), whereas the persistent asthma group had a per patient reduction of 0.99 prescriptions (P < .001). CONCLUSION: A targeted asthma intervention resulted in decreased hospitalization, emergency room, and physician visit costs in patients with persistent asthma.

Adolescent↗
PubMed2025

Cumulative Genetic Risk for Asthma Contributes to Disease Severity in Children with Asthma living in Urban Environments.

BACKGROUND: Childhood-onset asthma is highly heritable, with nearly 200 risk loci identified in genome-wide association studies. Aggregated polygenic risk scores can be used to quantify genetic predisposition to asthma, but their power to predict asthma severity in multi-ancestral groups has not been determined. OBJECTIVE: Our aim was to examine the predictive power of biobank-derived asthma polygenic risk scores in children with asthma living in urban environments. METHODS: We generated polygenic risk scores for asthma, derived from a large-scale genome-wide association meta-analysis, in four multi-ancestry asthma study cohorts of children living in urban environments. We assessed genetic predictions across different subphenotypes of asthma and tested for associations between genetic asthma risk and measures of asthma severity. RESULTS: Genetic asthma prediction was significantly stronger for more symptomatic asthma phenotypes (P<0.001). Polygenic risk scores were significantly higher in difficult-to-control vs. easy-to-control asthma (P=0.02). Genetic risk was also significantly associated with more frequent exacerbations (P=0.03), higher blood eosinophil levels (P=0.01), and lower lung function (P<0.001). CONCLUSION: Cumulative genetic risk for asthma is associated with disease severity and exacerbation risk in children with asthma living in urban environments.

Journal Article↗
PubMed2000

Does influenza vaccination exacerbate asthma? Analysis of a large cohort of children with asthma. Vaccine Safety Datalink Team.

CONTEXT: Although influenza vaccination is recommended for children with asthma, only a minority are vaccinated. One reason for low influenza vaccine coverage among children with asthma may be concern that influenza vaccination may induce an exacerbation of asthma. OBJECTIVE: To evaluate the safety of influenza vaccination in children with asthma, we studied the incidence of hospitalizations and emergency department visits for asthma following influenza vaccination. DESIGN: Retrospective cohort study-analysis of population-based computerized medical and vaccination records. SETTING: : Four large health maintenance organizations on the West Coast of the United States. SUBJECTS: Children with asthma 1 through 6 years of age, identified by search of computerized databases of medical encounters and pharmacy prescriptions. MAIN OUTCOME MEASURES: Exacerbations of asthma. RESULTS: In unadjusted analyses vaccination was associated with high rates of asthma exacerbations. However, after adjusting for asthma severity using a self-control method, the incidence rate ratios of asthma exacerbations after vaccination were 0.58 (95% confidence interval, 0.36-0.95), 0.74 (95% confidence interval, 0.47-1.17), and 0.98 (95% confidence interval, 0.76-1.27) during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination does not result in acute asthma exacerbations in children. Concern about possible exacerbation of asthma is not a valid reason to not vaccinate children with asthma against influenza.

Asthma↗
PubMed2004

Childhood asthma: exhaled markers of airway inflammation, asthma control score, and lung function tests.

Exhaled markers of airway inflammation become increasingly important in the management of childhood asthma. The aims of the present study are: 1) to compare exhaled markers of inflammation (nitric oxide, carbon monoxide, and acidity of breath condensate) with conventional asthma measures (lung function tests and asthma control score) in childhood asthma; and 2) to investigate the detectability of albumin, CRP, IL-6, IL-8, TNF-alpha, sICAM-1, and sTNF-R75 in the exhaled breath condensate (EBC) of asthmatic children. Thirty-two children with mild to moderate persistent asthma and healthy controls aged 6-12 years were studied. We measured exhaled NO and CO, and subsequently EBC was collected. Inflammatory mediators in EBC were measured using an enzyme-linked immunosorbent assay. Respiratory symptoms and asthma control were assessed using the asthma control questionnaire (ACQ) of Juniper et al. (Eur Respir J 1999;14:902-907). Exhaled NO showed a significant correlation with exhaled CO (r = 0.59, P < 0.05) and FEV1 (r = -0.59, P < 0.05), but not with ACQ score (r = 0.48, P = 0.06). Exhaled CO was correlated with prebronchodilator FEV1 (r = -0.45, P < 0.05), but not with asthma control (r = 0.18, P = 0.35). Acidity of EBC was significantly lower in asthmatic children than in healthy controls (P < 0.05), but did not correlate with any of the conventional asthma measures. We were not able to demonstrate the presence of CRP, IL-6, IL-8, TNF-alpha, sICAM-1, and sTNF-R75 in EBC. Albumin was found in two EBC samples of asthmatic children. We conclude that exhaled NO had a better correlation with lung function parameters and asthma control than exhaled CO and acidity of EBC, in mild to moderate persistent childhood asthma. However, exhaled NO, CO, and deaerated pH of EBC did not differ between asthmatic children and controls, possibly because of a too homogeneous and well-controlled study population. To further evaluate the clinical utility of exhaled markers in monitoring childhood asthma, more studies are required on a wider range of asthma severity, and preferably with repeated measurements of markers and of asthma control.

Adolescent↗
PubMed2005

Are psychiatric disorders associated with worse asthma control and quality of life in asthma patients?

BACKGROUND: Achieving good asthma control has become the major goal of asthma treatment. Studies have reported a high rate of psychiatric disorders among asthma patients, though the impact of these disorders on asthma control and quality of life remains unexplored. This study evaluated the prevalence of psychiatric disorders in 406 adult asthma patients, and associations between psychiatric status, levels of asthma control, and asthma-related quality of life. METHODS: Consecutive asthma patients presenting to the asthma clinic underwent a brief, structured psychiatric interview, completed the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), and reported the frequency of bronchodilator use in the past week. All patients underwent standard pulmonary function testing. RESULTS: A total of 34% (n=136) of patients had one or more psychiatric diagnosis, including major depression (15%), minor depression (5%), dysthymia (4%), panic disorder (12%), generalized anxiety disorder (5%), and social phobia (4%). Though there were no differences in pulmonary function, patients with versus without psychiatric disorders had worse ACQ and AQLQ scores and reported greater bronchodilator use, independent age, sex and asthma severity. CONCLUSIONS: Results suggest that psychiatric disorders are prevalent among asthmatics and are associated with worse asthma control and quality of life. Physicians should be aware of the potential risk of poorer asthma control and functional impairment in this population.

Adult↗
PubMed1997

Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma.

BACKGROUND: Intrinsic asthma is characterized by an increased number of activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchial mucosa. OBJECTIVE: This study was carried out to investigate the expression of alpha GM-CSF receptor (alpha GM-CSFr) messenger RNA and protein in the bronchial mucosa of patients with intrinsic or atopic asthma and of control subjects and to correlate the expression of alpha GM-CSFr to the number of EG2+ cells (eosinophils) and CD68+ cells (macrophages) and pulmonary function. METHODS: Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic subjects) were recruited, and FEV1 (percent predicted) and PC20 were measured before bronchoscopy. Endobronchial biopsy specimens were obtained and examined for membrane-bound alpha GM-CSFr by using in situ hybridization and immunocytochemistry. RESULTS: alpha GM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens from all four groups studied. There was no significant difference in the number of cells expressing alpha GM-CSFr mRNA and protein in patients with atopic asthma compared with atopic and nonatopic control subjects. However, the numbers of alpha GM-CSFr mRNA- and protein-positive cells were significantly higher in nonatopic patients with asthma compared with atopic patients with asthma and atopic and nonatopic control subjects (p < 0.001). In the patients with intrinsic asthma, the number of alpha GM-CSFr mRNA-positive cells per millimeter of basement membrane correlated with numbers of CD68+ cells (r2 = 0.87, p < 0.001) but not with EG2+ cells, and colocalization studies demonstrated that 80% of the cells expressing alpha GMCSFr mRNA were CD68+. The expression of GM-CSF was also significantly increased in patients with intrinsic asthma compared with those with atopic asthma and control subjects (p < 0.05). In addition, in intrinsic asthma, there was a correlation between alpha GM-CSFr mRNA and FEV1 (r2 = 0.61, p < 0.05). CONCLUSION: These results demonstrate that elevated numbers of cells expressing alpha GM-CSFr can be detected in nonatopic asthma but not in atopic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma.

Adult↗
PubMed2003

Sputum eosinophilia in cough-variant asthma as a predictor of the subsequent development of classic asthma.

BACKGROUND: A significant proportion of patients diagnosed with cough-variant asthma eventually manifest classic asthma signs, such as wheezing and dyspnoea. The aim of this study was to investigate whether the percentage of eosinophils and/or concentration of eosinophilic cationic protein (ECP) in sputum induced from patients with cough-variant asthma can predict the development of classic asthma. METHODS: Sixty-two children with cough-variant asthma were prospectively studied for 4 years. At the initiation of the study, sputum was induced with hypertonic saline, and the sputum samples were analysed for total and differential cell counts, and for ECP. Each subject was checked clinically at least every 3 months, and details of classic asthma signs experienced during the intervening periods were taken. RESULTS: Twenty-four (47.1%) of the 51 subjects available for follow-up developed signs of classic asthma, while 27 did not. The only significant difference in the sputum parameters between these two groups was a higher percentage of sputum eosinophils in subjects who developed classic asthma. A significant association was found between sputum eosinophil percentage and classic asthma development, but not between the concentration of sputum ECP and classic asthma development. CONCLUSION: Sputum eosinophilia in cough-variant asthma may be a correlate of the later development of classic asthma. This suggests that sputum differential cell counts may be useful in the clinical management of patients with cough-variant asthma, as they may enable the prediction of the subsequent classic asthma development.

Adolescent↗
PubMed1999

Chemotherapy reduces the prevalence of asthma symptoms in children with cancer: implications for the role of airway inflammation in asthma.

OBJECTIVE: Asthma is common in Australian children, with a prevalence of 30%. Airway inflammation is an important determinant of asthma symptoms. Chemotherapy used for the treatment of many childhood cancers suppresses inflammation. The prevalence of asthma symptoms in children treated with chemotherapy is unknown. METHODOLOGY: We therefore performed a survey of symptoms of asthma in children attending the oncology clinic at John Hunter Children's Hospital during the first 6 months of 1996. RESULTS: Fifty children aged 1-17 years were surveyed. Thirty-two of the children were in remission and had completed treatment with chemotherapy and 18 were currently undergoing treatment with chemotherapy. There was no significant difference in the prevalence of asthma in children before, during and after chemotherapy (26%, 22% and 34%), or in the prevalence of asthma in their siblings (28%). No child was classified as having persistent asthma while on chemotherapy and there was a significant reduction in the requirement for preventive asthma drugs 12% versus 0% (P = 0.03) being reported during chemotherapy. CONCLUSION: The prevalence of asthma in children who develop cancer is similar to their siblings and the same as the population as a whole. While asthma symptoms do not disappear completely during chemotherapy, the severity of asthma symptoms is less, with no need for asthma preventive treatment. The immunosuppressive side effects of the chemotherapy used in the treatment of childhood cancer appear to induce a remission in asthma symptoms. The ongoing requirement for bronchodilator therapy in patients whilst on chemotherapy suggests airway hyperreactivity persists in children while they are on chemotherapy. Prospective study of the airways of this group of patients promises to provide insights into the relationships between airway hyperreactivity, airway inflammation and asthma.

Adolescent↗