Asthma variability in patients previously treated with beta2-agonists alone.

Dorinsky PM.

Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

BACKGROUND: According to national asthma guidelines, asthma severity can be classified as intermittent, mild, moderate, or severe on the basis of lung function, symptoms, nighttime awakenings, and exacerbations. Although it is widely believed that patients might not remain consistently in any given severity category over time, few studies have examined this directly. OBJECTIVE: We sought to assess the variability in disease severity-control among patients with persistent asthma who have not yet received an asthma maintenance treatment. METHODS: We performed an analysis of asthma severity-control over time in placebo-treated patients (n = 85) from 2 randomized, double-blind, 12-week clinical trials in patients with asthma previously receiving beta(2)-agonists alone. Asthma severity-control was assessed on the basis of morning percent predicted peak expiratory flow, albuterol use, and symptoms. RESULTS: At baseline, all patients met the criteria for moderate or severe persistent asthma (mean FEV(1) of 64% of predicted value or albuterol use and symptoms on 4.7 and 6.0 days per week, respectively). The mean percentage of treatment weeks that patients met all criteria for intermittent, mild, moderate, and severe asthma were 9%, 14%, 71%, and 6%, respectively. On the basis of morning peak expiratory flow, patients were classified as having intermittent-mild, moderate, or severe disease on 52%, 41%, and 7% of days, respectively. With regard to days per week with albuterol use or asthma symptoms, patients spent 59% and 45% of weeks, respectively, in the intermittent and mild categories. CONCLUSION: Asthma control cannot be adequately assessed in many patients by using discrete point-in-time assessments of lung function, short-acting beta-agonist use, or asthma symptoms. This might lead to underestimation of disease severity and contribute to inadequate therapy and, ultimately, asthma morbidity.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14657863&dopt=Abstract asthma, asthma drug, asthma medicine




Association between beta2-adrenoceptor polymorphisms and asthma diagnosis among Mexican adults.

Barrera-Saldana HA.

Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon (UANL), Monterrey, Mexico.

BACKGROUND: Recent studies demonstrate that genetic variations in the human beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. OBJECTIVE: We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype. METHODS: This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis. RESULTS: A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). CONCLUSIONS: Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14657864&dopt=Abstract asthma, asthma drug, asthma medicine




Classifying asthma: disagreement among specialists.

Hen J Jr.

Children's Medical Group, 299 Washington Avenue, Hamden, CT 06518, USA. kirsten pol.net

OBJECTIVE: The asthma practice guidelines developed by the National Institutes of Health include a system for classifying asthma severity. The goal of the present study was to assess the interrater reliability of this classification system by measuring agreement among pediatric asthma specialists. DESIGN: A survey containing eight case summaries was mailed to 24 board-certified pediatric allergists and pulmonologists, who were asked to classify each case according to the national guidelines. The case summaries included the patient's medical history, physical examination, and chest radiograph and pulmonary function test results. Physicians were also asked to interpret the pulmonary function tests, to indicate the main factors used to classify each case (daytime symptoms, nighttime symptoms, pulmonary function testing, or various combinations), and to make treatment recommendations. kappa statistics were used to measure agreement. RESULTS: Fourteen of 24 surveys mailed (58%) were completed and returned. Agreement was poor for classifying asthma (kappa = 0.29; 95% confidence interval [CI], 0.25 to 0.33) and for the main factors used to make the classifications (kappa = 0.19; 95% CI, 0.14 to 0.23). Specialists exhibited higher agreement in their interpretation of pulmonary function tests (no asthma, kappa = 0.66; asthma on baseline, kappa = 0.53; exercise-induced asthma, kappa = 0.65). While physicians' treatment recommendations were consistent with their severity classifications, the low level of agreement in those classifications led to substantial variability in the treatments recommended. CONCLUSIONS: The low level of agreement among pediatric asthma specialists in classifying asthma severity suggests the need to refine the classification system used in the national guidelines to help ensure the consistent application of those guidelines.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14665495&dopt=Abstract asthma, asthma drug, asthma medicine




Detection of influenza, parainfluenza, adenovirus and respiratory syncytial virus during asthma attacks in children older than 2 years old.

Grumach AS.

Medical School, University of Sao Paulo, Brazil.

BACKGROUND: Viral upper respiratory tract infections (URTI) have been correlated with the onset of asthma attacks in children and viral identification was reported in 14-49 % of nasal samples. The aim of the present study was to detect influenza, parainfluenza, adenovirus and respiratory syncytial virus (RSV) in older children during acute asthma attacks. METHODS: A total of 104 children (2-14 years) were included in four groups: group I: asthmatics with acute attack and URTI; group II: asthmatics without URTI (group I children, 30 days later); group III: non-asthmatics with URTI; group IV: non-asthmatic, asymptomatic children. A diagnosis of URTI was considered when (3 symptoms (cough and/or sneeze, nasal obstruction, hypertrophy of turbinates, pain and/or retropharynx hyperemia, headache and fever) in asthmatics and at least 2 symptoms in non-asthmatics were present, starting within 7 days. Samples of nasal mucosa cells (n = 123) were collected, and culture and indirect immunofluorescence were carried out to identify respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1,2 and 3 and rhinovirus. RESULTS: Viral identification rates were higher in the asthmatic groups: 13.9 % in group I, 11.1 % in group II; 2.8 % in group III and 0 in group IV. The following viruses were identified: RSV 2/36, rhinovirus 1/36, adenovirus 1/36 and parainfluenzae 1/36 in group I; adenovirus 2/18 in group II; RSV 1/36 in group III. CONCLUSIONS: The rate of viral identification was higher in asthmatic children, whether symptomatic or not, suggesting a possible susceptibility to viral infections. Virus could also be a triggering factor in attacks, although it is not the most preponderant in older children.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14670285&dopt=Abstract asthma, asthma drug, asthma medicine




Does passive smoke exposure trigger acute asthma attack in children?

Dagli E.

Marmara University, Division of Pediatric Pulmonology, Istanbul, Turkey. bkaradag hotmail.com

The relationship between asthma and passive smoking has been well established. However, it is still not clear whether an acute asthma attack can be induced by acute smoke exposure. The specific aims of this study were: 1- To assess the degree of smoke exposure through urinary cotinine levels in asthmatic children during and 4 weeks after asthma attacks and, 2- To evaluate the reliability of parental questionnaires in asthmatic children by comparing the data obtained from cotinine measurements and parental reports. Thirty-two consecutive asthmatic children who were admitted to the emergency clinic were included in the study. Parents were asked to complete a questionnaire about their smoking habits and housing conditions. Urinary cotinine and creatinine levels were measured in children during and 4 weeks after the acute asthma attack. The mean age of the patients was 5.7 +/- 3.2 years. The mean attack rate was 3.5 +/- 3.8 per year. Thirty-eight percent of the patients were taking no preventive treatment. In 80 % of patients, urinary cotinine and creatinine ratios (CCR) were significantly above the non-exposed, non-smoker levels. However, CCR levels during acute asthma attacks were not higher than those measured 4 weeks after the acute attack (314.6 +/- 299.1 vs. 203.8 +/- 165.2 ng/mg respectively, p > 0.05). Although parental reports of passive smoke exposure was 71 %, CCR levels revealed that 81 % and 97 % of children were exposed to passive smoke during acute attacks and asymptomatic periods, respectively. In conclusion, although the proportion of children with acute asthma attacks who were exposed to passive smoking was high, the degree of passive smoke exposure was not higher during acute attacks. Parental questionnaires were found to be unreliable in reporting passive smoke exposure in asthmatic children during acute attacks.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14670286&dopt=Abstract asthma, asthma drug, asthma medicine




Increased risk of asthma among Finnish construction workers.

Uitti J.

Tampere Regional Institute of Occupational Health and Clinic of Occupational Medicine, Tampere University Hospital, Tampere, Finland.

AIM: To determine the risk of asthma among 7891 Finnish construction workers in the Pirkanmaa Region of southern Finland. METHOD: Retrospective cohort study of hospital records of the Tampere University Hospital. A population of Pirkanmaa paper mill workers (n=2686) and the Pirkanmaa working age population (n=252,500) served as reference populations. RESULTS: There were 147 new cases of asthma among the construction workers in 1991-1995. The annual rate was 37 per 10,000 workers and the odds ratio was 2.1 [95% confidence interval (CI)=1.2-3.6] for the women and 1.8 (95% CI=1.5-2.2) for the men when compared with the general working age population. In general, the risk of asthma among the paper mill workers did not differ from the risk of asthma among the general working age population. The construction workers had an increased risk for asthma, although the number of reported cases of occupational asthma was lower for the construction workers than for the paper mill workers or for the working population. CONCLUSION: Construction work, especially dusty tasks, was associated with an elevated risk of asthma. Thus the effect of exposure to irritant agents may have a role in the development of asthma among construction workers. For the most part, these cases of asthma do not meet the criteria for occupational asthma because the specified causal agent can not be defined. The aetiologic agents and mechanisms of asthma in construction work should be clarified for preventive measures.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14673127&dopt=Abstract asthma, asthma drug, asthma medicine




Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children.

The Lazio Association of Pediatric Allergology (APAL) Study Group.

Department of Pediatrics, San Camillo de Lellis Hospital, Rome, Italy.

BACKGROUND: It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children. METHODS: This was a case-controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests to 10 prevalent allergens at the time of examination. RESULTS: Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma. CONCLUSIONS: This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14674941&dopt=Abstract asthma, asthma drug, asthma medicine




Association of tumor necrosis factor polymorphisms with asthma and serum total IgE.

Park CS.

Department of Genetic Epidemiology, SNP Genetics Inc, Chongro-Gu, Seoul, Korea.

Tumor necrosis factors (TNF; TNFA and TNFB) are major pro-inflammatory cytokines that are thought to be important in the pathogenesis of asthma. However, the functions of genetic polymorphisms in these cytokines have not been thoroughly examined in the context of asthma pathology. In an effort to discover polymorphism(s) in genes whose variant(s) have been implicated in asthma phenotypes, we examined the genetic effects of TNF (TNFA and TNFB) polymorphisms on asthma and total serum IgE level. Seven common single-nucleotide polymorphisms (SNP) in TNF genes were genotyped in a Korean asthma cohort (asthmatics n=550, normal controls n=171). Six common haplotypes could be constructed in the TNF gene cluster due to very strong LD between TNFA and TNFB, located 13 kb apart on chromosome 6p21. One SNP (TNFA-308G>A) showed a significant association with the risk of asthma (P=0.0004). The frequency of TNFA-308A allele-containing genotype in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The protective effects of this polymorphism on asthma were also evident in separated subgroups by atopic status (P=0.05 in non-atopic subjects and P=0.003 in atopic subjects). The most common haplotype of the TNF gene (TNF-ht1[GGTCCGG]) was associated with total serum IgE (immunoglobulin E) levels in asthma patients, especially in non-atopic patients (P=0.004). Genetic variants of TNF might be involved in development of asthma and total serum IgE level in bronchial asthma patients. The results of this study could be helpful to understand the function of important TNF genes in asthma and IgE production.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14681301&dopt=Abstract asthma, asthma drug, asthma medicine