BACKGROUND:Uncontrolled asthma is characterized by variability. Current asthma guidelines recommend focussing on the achievement and maintenance of control but few studies have examined in detail, using composite measures of control, the stability and potential duration of control once achieved. In this post-hoc analysis of the results of the Gaining Optimal Asthma controL (GOAL) study, we examine the association between the level of asthma control achieved during the step-up phase of the study and the stability of control experienced during the maintenance phase.METHODS:GOAL was a 1-year, randomized, stratified, double-blind study of 3421 patients with uncontrolled asthma, which compared salmeterol/fluticasone propionate combination with fluticasone propionate in achieving two composite, guideline-based measures of control: totally controlled and well-controlled asthma. We analysed the proportion and duration of time spent in control, the effect of treatment on asthma stability, and the impact of asthma control stability on unscheduled use of healthcare resources.RESULTS:In patients achieving well-controlled or totally controlled asthma, at least well-controlled asthma was maintained for a median of almost 3 and 6 months, and for more than 85% and 95% of weeks of follow-up, respectively. A high level of stability was confirmed in a Markov analysis investigating transitional probability of change in control status. Variability in control was associated with increased probability of an unscheduled healthcare resource use (odds ratio: 1.06, P < 0.001).CONCLUSIONS:Most patients achieving guideline-defined control can maintain at least a similar level of control with regular, stable dosing, with little likelihood of losing control.

The present study examined the association between guideline-derived asthma control and health-related quality of life, assessed using the Asthma Quality of Life Questionnaire (AQLQ), in patients with uncontrolled asthma whose treatment was directed towards achieving the highest possible level of control.The present randomised, double-blind, parallel-group study compared the efficacy of fluticasone propionate (FP) and salmeterol/fluticasone propionate combination (SFC) in achieving two composite, guideline-derived measures of control: total control (TC) and well-controlled (WC) asthma. Not achieving these levels was classed as not well-controlled (NWC). Doses were augmented until patients achieved TC or reached the maximum dose. This dose was maintained for the remainder of the study. AQLQ was assessed at baseline and at each clinic visit.AQLQ scores improved throughout the study, reaching near-maximal levels in patients achieving TC and WC, and 52-week mean scores in the three control groups were statistically significantly different. Clinically meaningful improvements (mean change from baseline) were: TC group (SFC 1.9, FP 1.8), WC (SFC 1.5, FP 1.5) and NWC (SFC 1.0, FP 0.9).In conclusion, the treatment aimed at controlling asthma improves the health-related quality of life to levels approaching normal. The difference in Asthma Quality of Life Questionnaire scores between total control and well-controlled confirms that patients distinguish even between these high levels of control.

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions regarding the appropriate health care for specific circumstances. Guidelines are based on the scientific evidence on therapeutic interventions. The first asthma guidelines were published in the mid 1980s when asthma became a recognized public health problem in many countries. The Global Initiative on Asthma (GINA) was launched in 1995 as a collaborative effort between the NHLBI and the World Health Organization (WHO). The first edition was opinion‐based but updates were evidence‐based. A new update of the GINA guidelines was recently available and it is based on the control of the disease. Asthma guidelines are prepared to stimulate the implementation of practical guidelines in order to reduce the global burden of asthma. Although asthma guidelines may not be perfect, they appear to be the best vehicle available to assist primary care physicians and patients to receive the best possible care of asthma.

Background: The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control. Methods: Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid‐free, low‐ and moderate‐dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non‐parametric bootstrap. Cost‐effectiveness was compared with other treatments for chronic conditions. Result: Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well‐controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost‐effectiveness by stratum was £7600 (95% CI: £4800–10 700) per QALY gained for stratum 3; £11 000 (£8600–14 600) per QALY gained for stratum 2; and £13 700 (£11 000–18 300) per QALY gained for stratum 1. Conclusion: The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost‐per‐QALY figures that compare favourably with other uses of scarce health care resources.

The present authors explored the relationship between asthma control status, as measured by a derived Asthma Control TestTM (ACT) score, and the utilisation and cost of healthcare in Europe. Data were derived from a European survey of asthma patients. Frequency of healthcare resource use was identified from the dataset and per-patient mean cost of asthma management estimated. Drug costs were not available. The ACT score was derived from questions in the survey identical or similar to the items comprising the ACT. An ACT score was derived for 2,268 patients, of whom 48% (1,078) scored <20, suggesting their asthma was not well controlled, with 17% (381) scoring <15, suggesting poorly controlled asthma. The mean per-patient annual cost of asthma management for patients with a derived ACT of <15 was €1,604 (95% confidence interval: €1,219–2,084); for patients with a derived ACT score of 15–19, €512 (€404–660) and for patients with a derived ACT score of ≥20, €232 (€192–286). A higher derived ACT score was associated with significantly lower expenditure on asthma management. Worse asthma control, as measured by the derived Asthma Control TestTM score was associated with an increased requirement for unscheduled care and with higher cost.

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.

Asthma is a chronic, persistent inflammatory disease of the airways characterized by exacerbations of coughing, wheezing, chest tightness, and difficult breathing that are usually reversible, but that can be severe and sometimes fatal. The major factors contributing to asthma morbidity and mortality are underdiagnosis and inappropriate treatments. Most exacerbations reflect a treatment failure because they can be prevented if treatment of the disease is comprehensive and ongoing.The goals of asthma therapy are to improve the patient's quality of live by achieving and maintaining control of syptoms; preventing exacerbations; attaining normal lung function; maintaining normal activity levels, including exercise; and avoiding adverse effects from asthma medications.Recent studies have revealed thet inflammation is a critical feature in the pathogenesis of asthma, and therefore asthma therapy is predicated on medications to reverse and prevent this abnormality. Anti-inflammatory medications such as inhaled corticosteroids, sodium cromoglycate, and nedocromil are the primary therapy for the chronic care of all but mild, intermittent asthma. Further, early introduction or an increase in the dose of corticosteroids is an important component of treating severe exacerbations in order to speed resolutio of the exacerbation and prevent rucurrence.A six-part asthma management program is recommended for effective treatment: 1. Educate patients to develop a partnership in asthma management. Open communication, joint development of a treatment plan by the clinician and patient (guided self-management strategies), and encouragement of th efamily's efforts to improve asthma management will help patients gain the motivation, skill, and confidence to control their asthma. 2. Assess and monitor asthma severity with measures of lung function. Spirometry is recommended for the initial and scheduled periodic assessements of all asthma patients.A period of home peak flow monitoring may be useful for the initial assessement. Spirometry or peak expiratory flow monitoring is essential in hospital-based management of exacerbations. Home peak expiratory flow monitoring should be considered for patients who take medications daily. 3. Avoid or control asthma triggers. Environmental control measures are an important prevention strategy: Appropriate avoidance of triggers may reduce symptoms, the need for medication, and levels of nonspecific airway hyperresponsiveness. The role of specific immunotherapy in asthma management is under continual investigation. Currently available asthma management strategies with patient education, avoidance measures, and pharmacologic treatment usually provide good control of asthma. Immunotherapy may be considered when avoiding allergens is not possible, when appropriate medications fail to control symptoms, and where an effective specific immunotherapy is available. 4. Establish medication plans for chronic management. Because asthma is a dynamic as well as a chronic conditio, medication plans need to accomodate variability among patients as well as within individual patients over time. A stepwise approach to pharmacology therapy, in which the number and frequency of medications are increased with increasing classification of asthma severity, permits this flexibility. Once control of asthma is sustained for several weeks or months, a reduction in therapy - a step down - can be carefully considered and is needed to identify the minimum therapy required to maintain control. The four steps to achieve and maintain control of asthma emphasize that anything more than mild occasional asthma requires daily therapy with anti-inflammatory agents and that patients should not rely on frequent use of bronchodilator agents to control their asthma. Figure 4 in Chapter 2 summarizes the treatment recommended in the stepwise approach.A color-coded asthma zone management system for patients has been developed to help patients understand and monitor the variable nature of this chronic disease. and take appropriate actions to maintain control of asthma. The forst (Green Zone) reflects therapy required to achieve the goals of therapy, i.e., maintaint control of symptoms and prevent exacerbations. The stepwise approach described above is used to identify the minimum amount of medication required to maintain control of the patient's asthma. The second (Yellow Zone) reflects a deterioration in asthma control and indicates a need to temporarily increase treatments as well as a need to review the Green Zone plan. The third (Red ZOne) signals a medical alert, and immediate steps to amnage the exacerbation are required, with subsequent adjustment of the Green Zone plan. Written plans for each zone are essential to improve patient adherence. 5. Establish plans for managing exacerbations. Exacerbations usually reflect either a failure of chronic management or exposure to a noxious agent. Severe exacerbations often reflect inadequate action at the onset of the exacerbation. Therapy for exacerbations emphasizes the early introduction of corticosteroids as well as frequent administration of inhaled beta2-agonists. Patients need a written plan for recognizing signs that asthma is worsening, for when, how, and for how long to increase treatment, and for reaching medical care. 6. Provide regular followup care. Patients need regular supervision and support by a clinician who is knowledgeable about asthma. Continual monitoring is essential to assure that therapeutic goals are met.The following report elaborates upon each of these six parts of effective asthma management. It provides more detailed recommendations and documentation from the scientific literature.

A community based, prospective study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken. One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol. Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a 'partially double-blind' manner. The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1. All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority. Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone, particularly when inhaled steroids were started in relatively high dosage.

Patient compliance with a standardized incremental regime of inhaled anti-asthma therapy has been assessed in alarge, prospective study in general practice. Urine salbutamol estimations were made in 30 patients who had the largest improvement with therapy (mean increase in FEV 1 0·451 above baseline: Responsive) and in 30 patients whose airflow obstruction failed to improve (FEV 1 -0·141: Nonresponsive). The urine salbutamol concentrations rose over the 9 month period in the responsive patients as expected with the incremental doses prescribed, and were significantly higher than urine levels in nonresponsive patients at two dose levels. Poor compliance with prescribed inhaled therapy is an important cause of persistent morbidity from asthma.

Peripheral blood mononuclear cells (PBMC) were isolated from seven normal subjects, eight asthmatic subjects clinically sensitive to corticosteroids (CS), and eight asthmatic subjects clinically resistant to corticosteroids (CR). PBMC were cultured at 37 degrees C for 24 h in the absence or presence of 10(-16) to 10(-4) M hydrocortisone. Calcium ionophore (A23187)-activated neutrophils (PMN) primed by supernatants of PBMC from asthmatic subjects cultured in the absence of hydrocortisone generated approximately threefold more leukotriene B4 than PMN primed by supernatants of PBMC from normal subjects (P less than 0.05). Incubation of PBMC derived from CS subjects with 10(-8) M hydrocortisone completely inhibited the production of the enhancing activity (P less than 0.01), whereas in CR subjects hydrocortisone at concentrations up to 10(-4) M did not suppress the release of enhancing activity. The enhancing activity was produced by monocytes. Enhancing activity eluted with an Mr of 3,000 D and a pI of 7.1. It eluted at 10% acetonitrile after reverse-phase HPLC. The activity was destroyed by heating to 60 degrees C for 60 min and was sensitive to pronase treatment. The purified factor also enhanced superoxide generation by PMN which had been stimulated submaximally by phorbol myristate acetate.