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Prevalence and risk factors of work related asthma by industry among United States workers: data from the third national health and nutrition examination survey (1988-94).

OBJECTIVES: To estimate the prevalence of work related asthma and work related wheezing in United States workers. To identify high risk industries that could be targeted for future intervention. To determine the population attributable risk of work related asthma and work related wheezing. METHODS: The third national health and nutrition examination survey, 1988-1994 (NHANES III) was analyzed to determine the prevalence of work related asthma and wheezing and to identify initially defined industries at risk among United States workers aged 20 and older. Separate logistic models were developed with work related asthma and work related wheezing as outcomes. Work related asthma was defined as affirmative response to questions on self reported physician diagnosed asthma and work related symptoms of rhinitis, conjunctivitis, and asthma. Work related wheezing was defined as affirmative response to questions on self reported wheezing or whistling in the chest in the previous 12 months and work related symptoms of rhinitis, conjunctivitis, and asthma. All analyses were adjusted for age, sex, smoking, and atopy. RESULTS: The prevalence of work related asthma was 3.70% (95% confidence interval (95% CI) 2.88 to 4.52) and the prevalence of work related wheezing was 11.46% (95% CI 9.87 to 13.05). The main industries identified at risk of work related asthma and wheeze included the entertainment industry; agriculture, forestry, and fishing; construction; electrical machinery; repair services; and lodging places. The population attributable risk for work related asthma was 36.5% and work related wheezing was 28.5%. CONCLUSIONS: The findings provide impetus for further research and actions by public health professionals which prioritise occupational asthma on the public health agenda. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace.

Adult↗

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood.

BACKGROUND: The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma. METHODS: Healthy non-selected newborn infants (n = 1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on > or = 2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (> or = 4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS: The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION: The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.

Adolescent↗

Prevalence of untreated asthma in a population sample of 6000 older adults in Bristol, UK.

BACKGROUND: A study was undertaken to estimate the prevalence of untreated asthma in older adults. METHODS: A cross sectional population based survey of 6000 men and women aged 65 years and over was performed in 21 general practices in north Bristol, south west England. The main outcome measure was untreated asthma as defined by a two stage process comprising a respiratory questionnaire (symptoms suggestive of asthma or doctor diagnosed asthma not receiving respiratory treatment) followed by lung function tests (significant reversibility following bronchodilators or corticosteroids and/or significant within day variability in peak expiratory flow). RESULTS: 4792 of the 6000 participants (80%) completed the respiratory questionnaire and, of those not receiving respiratory treatment, 55 reported a previous doctor diagnosis of asthma and a further 696 had symptoms suggestive of asthma. Lung function testing in 280 of 501 randomly selected individuals from these groups resulted in 38 being defined as having asthma and an estimated population prevalence for untreated asthma of 2.4% (95% CI 1.6% to 3.6%) in men and 1.2% (95% CI 0.7% to 2.1%) in women. Most subjects (84%) with untreated asthma had moderate or severe disease. Untreated asthma was most common in individuals with doctor diagnosed asthma (21%) and those with breathlessness or wheeze (13-20%). CONCLUSION: Untreated asthma in the elderly is a common and important problem. Opportunistic use of appropriate lung function tests in older people with a history of doctor diagnosed asthma or wheeze or breathlessness at rest could identify untreated asthmatics who might benefit from treatment.

Aged↗

Asthma in preschool children: prevalence and risk factors.

BACKGROUND: The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children. METHODS: Parents of children aged 3-5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma and having cough or wheeze in the last 12 months and having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens. RESULTS: The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma. CONCLUSIONS: Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.

Asthma↗

Underdiagnosed asthma in South Australia.

BACKGROUND: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. METHODS: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age>18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: "Have you ever had asthma?"; "Has it been confirmed by a doctor?"; "Do you still have asthma?" determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician's diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. RESULTS: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor's diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. CONCLUSION: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.

Adult↗

Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers.

BACKGROUND: A protective effect of endotoxin exposure on atopy and asthma in farmers' children has been postulated. Studies of adult farmers have shown conflicting results but often lack exposure data. The prevalence of asthma in farmers with different exposure levels to microbial agents and irritant gases was compared. METHODS: Atopy was defined as a positive response to multiple radioallergosorbent tests (RAST) with a panel of 10 common respiratory allergens, and asthma was ascertained by a questionnaire using a stratified sample (n = 2169) of a farming population from south-eastern Norway. Exposure of farmers to total dust, fungal spores, bacteria, endotoxins, and ammonia was assessed by exposure measurements. RESULTS: The prevalence of asthma was 3.7% for physician diagnosed asthma and 2.7% for current asthma. The prevalence of atopy was 14%, but most asthmatic subjects were non-atopic (80%). Compared with farmers without livestock, (1) asthma was significantly higher in cattle farmers (OR(adj) 1.8, 95% CI 1.1 to 2.8) and pig farmers (OR(adj) 1.6, 95% CI 1.0 to 2.5), (2) non-atopic asthma was significantly higher in pig farmers (OR(adj) 2.0, 95% CI 1.2 to 3.3) and in farmers with two or more types of livestock (OR(adj) 1.9, 95% CI 1.1 to 3.3), and (3) atopic asthma was less common in farmers with two or more types of livestock (OR(adj) 0.32, 95% CI 0.11 to 0.97). Exposure to endotoxins, fungal spores, and ammonia was positively associated with non-atopic asthma and negatively associated with atopic asthma. No associations were found with atopy. CONCLUSIONS: Exposure to endotoxins and fungal spores appears to have a protective effect on atopic asthma but may induce non-atopic asthma in farmers.

Adult↗

TNF-alpha dysregulation in asthma: relationship to ongoing corticosteroidtherapy.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy. OBJECTIVES: To examine the ability of peripheral blood mononuclear cells (PBMC) from three different groups of patients with asthma requiring varying amounts of inhaled corticosteroids (ICS) for clinical control, and to examine cells from age- and sex-matched nonasthmatic patients to produce TNF-alpha. DESIGN: All patients with asthma had a positive methacholine challenge test. 'High dose' ICS patients with asthma required ICS greater than or equal to 800 microg/day. 'Medium dose' patients with asthma were on less than or equal to 500 microg/day of ICS, whereas 'no ICS' patients with asthma had received no ICS for at least three months. Each patient with asthma was examined in parallel with an age- and sex-matched, nonasthmatic, nonatopic control subject. Cells were cultured (with or without the addition of potential stimulators phytohemagglutinin, lipopolysaccharide, formyl-methionine-leucine-phenylalanine or antihuman CD3), and TNF-alpha production was assessed by ELISA. MAIN RESULTS: PBMC from both high dose ICS (n=8) and no ICS (n=11) patients with asthma produced more than twice the amount of TNF-alpha than cells from matched nonasthmatic control patients (P<0.01) when cultured alone or in the presence of each stimulus (P<0.05). In contrast, there was no significant difference in TNF-alpha production between medium dose ICS patients with asthma and control patients. A group of asymptomatic atopic patients (n=6) did not have an increased level of TNF-alpha production. CONCLUSIONS: Increases in TNF-a production within the PBMC compartment can be observed in both patients with asthma receiving high dose ICS and in a group of patients with mild asthma receiving no ICS therapy, but not in patients with asthma receiving a medium dose of ICS or atopic patients.

Administration, Inhalation↗

Gastroesophageal reflux and asthma: can the paradox be explained?

BACKGROUND AND OBJECTIVE: The reported effects of asthma on gastroesophageal reflux (GER), effects of GER on asthma and the effects of antireflux therapy on asthma are conflicting. The purpose of this paper is to review the evidence for a relationship between the two conditions. DESIGN: A search of the MEDLINE 1966 to 1999 database, combining the terms GER and asthma, was used to identify studies of the effects of acid perfusion of the esophagus, the physiological equivalent of GER and the effects of both medical and surgical antireflux therapy on asthma. Bibliographies of the identified papers were also reviewed. MAIN RESULTS: The collected evidence suggests that GER causes asthma symptoms but has minimal effects on pulmonary function. Both medical and surgical antireflux therapy can improve asthma symptoms and asthma medication requirements without improving pulmonary function. The paradox of GER causing symptoms without affecting pulmonary function may be because of the retrosternal discomfort that accompanies GER increases minute ventilation and respiratory sensation. CONCLUSIONS: Despite an extensive body of literature, many questions remain about the relationship between GER and asthma. A review of the data suggests a strong association between the two conditions, and that GER worsens asthma symptoms without affecting pulmonary function. Asymptomatic GER does not worsen asthma. Antireflux therapy may have a role in asthma patients with symptomatic GER, possibly being most beneficial for those with reflux-associated respiratory symptoms. Unfortunately, many studies contain flaws such as a lack of controls and small sample sizes. Further properly designed controlled trials, including ones that measure the effects of GER and antireflux therapy on quality of life, are needed to understand better the role of GER in asthma.

Animals↗

Adult Asthma Consensus Guidelines update 2003.

BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines. OBJECTIVES: To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management. METHODS: Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed. RESULTS: The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta2-agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education. CONCLUSION: The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.

Adrenal Cortex Hormones↗

Inhaled corticosteroid therapy does not control asthma.

BACKGROUND: Randomized clinical trials demonstrate efficacy and show that inhaled corticosteroid therapy can control asthma, but details concerning their effectiveness in achieving this goal in the community are lacking. OBJECTIVES: To determine whether inhaled corticosteroid therapy is effective in controlling asthma and to examine the rates of asthma control in relation to inhaled corticosteroid use outside the realm of randomized controlled trials. METHODS: Different populations were examined cross-sectionally to determine whether self-reported use of inhaled corticosteroids was associated with control of asthma. Subjects with asthma in the community and those attending a university-based asthma program were studied. The definition of asthma control was based on the recommendations of the Canadian Consensus Report. The elements of asthma control were examined in the context of the subject's stated use and dose of the inhaled corticosteroid. RESULTS: Asthma was controlled in 20% (95% CI 18.7% to 21.3%) of the 3427 subjects included in the present study. Only 15% (95% CI 13.5% to 16.5%) of the 2437 subjects using inhaled corticosteroids exhibited asthma control compared with 33% (95% CI 31.1% to 35.9%) of the 990 subjects not using inhaled corticosteroids (P<0.000001). CONCLUSIONS: Although it is known that inhaled corticosteroid therapy can result in asthma control in most individuals with asthma, the present study has shown that this result may not be attained outside the realm of randomized clinical trials. Inhaled corticosteroid use for asthma in a 'real world' setting appears to reflect disease severity.

Adolescent↗

A repeat polymorphism in interleukin-4 gene is highly associated with specific clinical phenotypes of asthma.

BACKGROUND: IL-4 is a determining factor in immunologic mechanisms to allergy and inflammation. The authors designed a case-controlled study to investigate the potential association of a repeat polymorphism in IL-4 gene with specific clinical phenotypes of asthma. METHODS: The authors used the polymerase chain reaction to characterize the variation of the IL-4 intron 2 region in 145 unrelated Tunisian patients with asthma and 160 healthy control subjects. In order to strengthen the case-controlled study, analysis of IL-4 polymorphism was performed in families of several asthmatic patients. Asthma scores were determined and correlated with this polymorphism. RESULTS: Analysis of IL-4 polymorphism in patients with allergic asthma and in control subjects demonstrated a significant association between the IL-4 A1 allele and asthma. Further evidence of the strong association found between IL-4 intron 2 polymorphism and asthma was provided by the finding that asthma is transmitted in association with the inheritance of the IL-4 A1 marker. When patients were stratified into two groups according to the degree of the severity of asthma, the IL-4 A1 allele was specifically not associated with mild asthma, but highly associated with the moderate and severe forms of the disease. The relative risk (RR) of severe asthma is especially high in patients carrying the A1/A3 genotype (RR = 3.94, p = 0.0001). Conversely, a major decrease in the frequency of the IL-4 A3/A3 genotype was observed in patients with severe asthma, resulting in a significantly negative RR of this clinical phenotype of asthma (RR = 0.165, p = 0.0001). CONCLUSIONS: Tunisian persons carrying the IL-4 A1/A3 genotype may have an increased risk of severe asthma.

Adolescent↗

Neutrophilic inflammation in severe persistent asthma.

Airway inflammation in severe asthma is not well characterized but may involve neutrophils. We have compared induced sputum profiles in patients with asthma of varying severity and normal control subjects. We have also measured exhaled nitric oxide (NO) as a noninvasive marker of inflammation. Asthma severity was based on clinical features before treatment and the minimum medication required to maintain asthma control at the time of sputum induction, and classified as (1) mild: treated with inhaled beta(2)-agonist occasionally (n = 23; FEV(1), 91%; peak expiratory flow (PEF) variability, 10.5%), (2) moderate: requiring medium dose inhaled steroids to maintain control (n = 16; FEV(1), 88%; PEF variability, 9.1%), and (3) severe: despite using inhaled and oral steroids (n = 16; FEV(1), 61%; PEF variability, 36.2%). The asthmatic patients were nonsmokers with evidence of airway hyperresponsiveness or reversible airway obstruction, and free of respiratory tract infection for at least 6 wk. Sputum revealed significantly increased neutrophil numbers in severe asthma (53.0 [38.4- 73.5]%, p < 0.05) compared with mild asthma (35.4 [29.8-46.1]%) and normal control subjects (27.7 [20.6-42.2]%). Interleukin-8 (IL-8) and neutrophil myeloperoxidase (MPO) levels were increased in asthmatic patients, with the highest levels in severe asthma. Eosinophil numbers were increased in both mild and severe asthma, but interleukin-5 (IL-5) levels were highest in mild asthma, whereas eosinophil cationic protein (ECP) levels were highest in severe asthma. Exhaled NO levels were highest in asthmatic untreated with corticosteroids, but there was no significant difference between asthmatics using corticosteroids (Groups 2 and 3), regardless of clinical asthma severity. This confirms the role of eosinophils in asthma but suggests a potential role of neutrophils in more severe asthma.

Adult↗

Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?

To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophils and neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 +/- 6.3 in slow-onset; 9.7 +/- 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 +/- 2.0 in slow-onset; 16.8 +/- 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Immunomodulatory effects of melatonin in asthma.

Patients with nocturnal asthma demonstrate circadian variations in airway inflammation. We hypothesized that melatonin, a circadian rhythm regulator, modulates circadian inflammatory variations in asthma. The effect of melatonin stimulation on peripheral blood mononuclear cell cytokine production was evaluated at 4:00 P.M. and 4:00 A.M. in normal control subjects, patients with nocturnal asthma, and patients with non-nocturnal asthma. Melatonin was proinflammatory, causing significantly increased production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha at 4:00 P.M. and 4:00 A.M. in all subject groups (range, 12.8 +/- 3.3 to 131.72 +/- 16.4%, p < or = 0.0003). The observed increases in cytokine production did not change between 4:00 P.M. and 4:00 A.M. in control subjects or in patients with nocturnal asthma (p > 0.05, both cases). At 4:00 P.M., the cytokine response to melatonin of patients with nocturnal asthma was greater than that of control subjects or patients with non-nocturnal asthma and did not change significantly at 4:00 A.M. At 4:00 P.M., the cytokine response of patients with non-nocturnal asthma was less than that of patients with nocturnal asthma and rose significantly at 4:00 A.M. (p = 0.0001, all comparisons). Melatonin is proinflammatory in both patients with asthma and healthy subjects. Patients with nocturnal asthma demonstrate the largest daytime cytokine response and cannot be further stimulated at 4:00 A.M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma.

Adjuvants, Immunologic↗

Zafirlukast: the first leukotriene-receptor antagonist approved for the treatment of asthma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of zafirlukast. Therapeutic issues regarding the use of a leukotriene-receptor antagonist as prophylactic antiinflammatory therapy for asthma are also discussed. DATA SOURCES: A MEDLINE search was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Pharmacokinetic and dosing information were abstracted from the product labeling. STUDY SELECTION: All available published articles describing double-blind, placebo-controlled trials of both oral and aerosol zafirlukast in patients with asthma or rhinitis were reviewed. These included single-dose studies with zafirlukast against exercise, allergen, leukotriene D4 (LTD4), and platelet-activating factor (PAF) challenges, and 6- and 13-week trials in patients with asthma. Studies describing clinical trials with long-term use or comparisons with other asthma medications as reported in abstracts are also included. DATA EXTRACTION: Information on the safety and efficacy of zafirlukast from single- and multiple-dose studies was evaluated on the basis of statistical significance relative to placebo treatment. DATA SYNTHESIS: Zafirlukast, a potent and selective antagonist of the cysteinyl leukotriene receptor, blocks leukotriene-mediated pathologic events in both experimental animal and clinical disease models. Zafirlukast antagonizes LTD4-, PAF-, and exercise-induced bronchoconstriction, and blocks both early- and late-phase responses following allergen provocation in patients with atopic asthma. Greater efficacy is noted following oral administration than with aerosol dosing, presumably because of the enhanced delivery of drug when ingested rather than inhaled. CONCLUSIONS: Zafirlukast is the first orally active leukotriene-receptor antagonist approved by the Food and Drug Administration for the prophylactic and chronic treatment of asthma. Since the leukotrienes play an important role in the underlying inflammatory processes of asthma, zafirlukast represents a new antiinflammatory option available in an oral dosage form. It is clear that this agent has therapeutic activity in patients with asthma, but its effectiveness relative to other antiasthma medications still needs confirmation. Data from clinical studies support the use of zafirlukast as first-line therapy in patients with mild-to-moderate asthma. Further research is needed to establish its role as an add-on agent for patients with severe asthma, aspirin-sensitive asthma, and both allergies and asthma. In addition to having a favorable safety and efficacy profile, zafirlukast has the advantage of being an oral agent with twice-daily dosing; these attributes offer the potential for greater patient adherence to pharmacotherapy and, thereby, improved control of asthma symptoms.

Animals↗

Achieving guideline-based asthma control: does the patient benefit?

Asthma management guidelines define asthma control, but the outcome criteria used do not include the patient's own assessment of their health. The objective of the present study was to determine the association between the achievement of asthma control, as defined by the Global Initiative for Asthma (GINA) guidelines, and patient-assessed asthma-related quality of life (QOL), particularly whether maximal or near-maximal QOL scores were attainable. Clinical data from three studies that compared salmeterol/fluticasone propionate combination therapy (SFC) with other treatments in patients with persistent asthma were retrospectively analysed. Achievement of asthma control was determined over an 8-week period in each study according to six parameters derived from the GINA guideline treatment goals. Asthma Quality of Life Questionnaire (AQLQ) scores (a 7-point scale, where 1=severe impairment and 7=no impairment) were analysed by treatment group for well-controlled and not well-controlled patients. The analysis showed that, across a range of severities, well-controlled asthma patients had consistently higher AQLQ scores at endpoint and larger AQLQ improvements from baseline, than patients who were not well controlled. For many well-controlled patients, endpoint scores approached 7, indicating little or no impact of asthma on their QOL. However, AQLQ scores of not well-controlled patients also improved substantially in some treatment groups, particularly the SFC group. These results suggest a relationship between the achievement of guideline-based asthma control and improvements in quality of life to levels where there is little or no impact of asthma on quality of life. Guideline-based asthma control is therefore beneficial to the patient and should be tested in prospective studies.

Albuterol↗

Asthma severity and medical resource utilisation.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1-November 30, 1999, and 500 consecutive patients with asthma, aged 18-55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros (Euros) for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be Euros 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to Euros 720, Euros 1,046, Euros 1,535 and Euros 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.

Activities of Daily Living↗

Breaking new ground: challenging existing asthma guidelines.

BACKGROUND: While we have international guidelines and various national guidelines for asthma diagnosis and management, asthma remains poorly controlled in many children and adults. In this paper we review the limitations of current asthma guidelines and describe important issues and remaining questions regarding asthma guidelines for use, particularly in primary care. DISCUSSION: Clinical practice guidelines based on evidence from randomized controlled trials are considered the most rigorous and accurate. Current evidence-based guidelines are written predominantly from the perspective of the patient with a clear-cut asthma diagnosis, however, and tend not to consider the heterogeneity of asthma or to accommodate individual patient variations in response to treatment or their needs, differences in practice settings, or local differences in availability and cost of therapies. The results of randomized controlled trials, which are designed to establish efficacy of treatment under ideal conditions, may not apply to 'real-world' clinical practice, where patients are unselected, monitoring is less frequent, and effectiveness--the benefit of treatment in routine clinical practice--is the most relevant outcome. Moreover, most guidelines see asthma in isolation rather than considering other factors that may impact on asthma and response to asthma therapy, particularly age, allergic rhinitis, cigarette smoking, adherence, and genetic factors. When these links are recognized, guidelines rarely provide practical recommendations for treatment in these scenarios. Finally, there is some evidence that general practitioners are not convinced of the applicability of asthma guidelines to their practice settings, especially when those writing the guidelines principally work in specialist practice. CONCLUSION: Developing country-specific guidelines or, ideally, local guidelines could provide more practical solutions for asthma care and could account for regional factors that influence patient choice and adherence to therapy. Pragmatic clinical trials and well-designed observational trials are needed in addition to randomized controlled trials to assess real-world effectiveness of therapies, and such evidence needs also to be considered by guideline writers. Finally, practical tools to facilitate the diagnosis and assessment of asthma and factors responsible for poor control, such as associated allergic rhinitis, limited adherence, and smoking behavior, are needed to supplement treatment information provided in clinical practice guidelines for asthma.

Adult↗