Use of Long Term Antiinflammatory Agents

Asthma Free Forever

Asthma Free Forever By Jerry Ericson

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When the NHLBI guidelines were constructed and released in 1991, it was widely assumed that anti-inflammatory controller agents must be initiated early (even in mild persistent asthma) to prevent progressive decline in lung function that would ensue due to unmitigated airways inflammation and subsequent remodeling. This theory was based on retrospective evidence in childhood asthma studies showing that more severe and irreversible airway obstruction was significantly associated with a delay in initiation of an ICS. More recent long-term prospective data from the Childhood Asthma Management Program (CAMP) study collected in asthmatic children treated for five years have failed to show significant differences between placebo, cromolyn, and ICS treated patients in changes in FEV1 (30). However, the ICS (budesonide) treated group had fewer hospitalizations, urgent visits for asthma, and reduced airway responsiveness compared to nedocromil. Accelerated decline in lung function was significantly associated with low-post bronchodilator FEV1 at pretreatment baseline, and not related to treatment intervention (31). Based on this study, the purported preventive effect of anti-inflammatory drugs on airway remodeling in uncertain but there are clearly other benefits of ICS drugs that affect long-term disease control. Other investigations of disease outcomes associated with institution of asthma guidelines and/or long-term ICSs are discussed below.

There is good evidence that early institution of ICSs after an asthma diagnosis is established and is associated with reduced risk of subsequent hospitalizations. This was demonstrated in a large nested case control study conducted in Canada for 13,563 newly treated asthmatic subjects in which patients initially prescribed ICSs were compared with those prescribed theophylline for a maximum of 12 months of treatment (32). Those patients prescribed ICSs were 40% less likely to be admitted to the hospital for asthma than patients using theophylline. In this same cohort of patients in the Saskatchewan health system followed between 1977 and 1993, the probability of readmission for asthma was evaluated in relation to whether inhaled corticosteroids were prescribed after initial hospital admission (33). Patients who received regular treatment with ICSs were 40% less likely to be readmitted for asthma. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval and 39% in the rate of readmission) (34). This population was also evaluated with possible association between ICS usage and asthma-related deaths (35). After adjustment for covariates, patients receiving one or more metered-dose inhalers of beclomethasone per month were shown to have a significantly lower risk of fatal and near-fatal asthma (odds ratio = 0.1). The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. The same group of investigators evaluated asthma death related to corticosteroid usage, using a case-control design (36). A dose-response analysis estimated that asthma death rates decreased by 21% with each additional ICS canister used during the previous year (adjusted rate ratio = 0.79). Thus, the beneficial effects in important asthma disease outcomes demonstrated in these studies clearly validate asthma guideline treatment recommendations of long-term use of ICSs in patients with moderate and severe asthma.

Since asthma treatment guidelines were introduced in Japan in the 1990s, the impact of introduction of leukotriene inhibitors and ICSs on asthma mortality was assessed from the period spanning 1987 to 1999 (37). The rate of asthma deaths decreased with increasing use of leukotriene receptor antagonists and inhaled corticosteroids. The rate of asthma deaths was 0.96 per 1 million 25-day treatment courses of inhaled corticosteroids and 0.80 for every 1 million 25-day treatment courses of leukotriene antagonists. This result suggests that the increased use of anti-inflammatory agents in the Japanese health care system may have partially contributed in some way to the decrease in asthma mortality.

Boulet et al. examined a large population of asthma patients who were suboptimally controlled according to Canadian asthma consensus guidelines (38). In separate surveys of patients with uncontrolled asthma and their physicians, 66% of patients and 43% of physicians rated control of asthma symptoms as adequate to very good. These findings indicate that physicians are still not utilizing diagnostic guidelines to assess asthma severity and highlight the need to more effectively disseminate this information to both physicians and their patients. A survey of 445 asthmatic patients in New Zealand used the GINA guidelines as a gold standard for defining asthma control and, on this basis, revealed that 93% of adults and 90% of children were suboptimally controlled (39). Another large survey of parents of children with asthma reported that despite suboptimal control defined by guidelines in 49% of children and under treatment for the level of asthma severity, 89% of parents were satisfied with treatment outcomes (40). Prescription data has also been examined to indirectly assess impact of published guidelines. A three-year survey (1996-1998) of 13,000 patients receiving p-agonist prescriptions in British Columbia revealed a discouraging trend that ICS usage decreased over time (41). As mentioned, a recently published international survey of asthma treatment and severity indicates that only a small minority of patients (< 30%) in all countries surveyed are receiving preventative therapy (10). This suggests that outcomes of treatment and even adherence with physician and guideline directed therapy could be negatively influenced by low parental expectations.

A randomized controlled trial was conducted in 81 general practices in the United Kingdom in which the medical providers were issued abbreviated asthma guidelines. Outcomes were determined by measuring adherence to asthma recommendations among patients. In this brief study, issuance of brief guidelines did not improve adherence to recommendations related to asthma treatment (42). Bender et al. recently reviewed published studies pertaining to outcomes of adherence interventions (43). These authors noted that in 50% of studies experimental interventions do not improve adherence. They acknowledged that a strong physician-patient relationship enhances adherence, highlighting the need for physicians to be familiar enough with evidence-based treatment guidelines to impart important information to their patients with asthma.

Barr et al. (44) assessed adherence to the NAEPP medication guidelines among 5107 elderly female asthma patients. Fifty-seven percent of mild persistent, 55% of moderate persistent, and 32% of severe persistent asthma patients were found to be adherent with asthma medication guidelines. Based on a multivariate analysis, non-adherence was associated with severe asthma, increasing age, lower socioeconomic status, current smoking, earlier onset of asthma, and number of comorbid medical conditions. This study underscores the minimal impact the guidelines have had in the community, which is likely due to ineffective physician education.

Management of Acute Exacerbations

Guideline reports recommend written action plans for moderate or severe asthmatics to guide self-management of acute exacerbations and particularly those who have previously been hospitalized or have undergone mechanical ventilation for near-fatal attacks. The GINA report emphasizes that high-risk patients who have previously received mechanical ventilation are at a 19-fold risk of requiring mechanical ventilation in subsequent attacks (5). A written ''action plan'' should contain emergency treatment instructions on how to recognize and manage acute exacerbations. Essential components of the action plan should include: instructions on how exacerbations can be recognized by early decrements in lung function (i.e., PEFR); prompt communication with the clinician; prompt and early intensification of therapy, including initiation of a burst of oral corticosteroids; and immediate removal from relevant allergens or irritants (2). Several studies have examined outcomes of implementation of guideline recommendations for managing acute exacerbations, including possible benefits of written action plans. The practice of doubling inhaled corticosteroids doses as opposed to administering oral corticosteroids for acute mild exacerbations has already been addressed earlier in this chapter. The GINA report, recognizing that there is limited evidence to support the latter strategy, recommend systemic steroids for all but the mildest exacerbations. Systemic corticosteroids should be instituted in any patient not showing a prompt response to an inhaled short-acting p-agonist (5).

There is evidence that emergency room physician compliance with published guidelines pertinent to managing acute exacerbations is suboptimal (45,46). There have also been important studies that have evaluated clinical outcomes related to administration of self-management and action plans for managing acute exacerbations. Cote et al. performed an investigation of 98 asthma patients presenting with acute exacerbations (47). Patients were assigned to usual treatment, limited education on a self-action plan by the emergency physician, or a structured educational program emphasizing self-management of asthma exacerbations. At 12 months, only the group receiving structured education was found to have significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. The number of unscheduled medical clinic visits for asthma was significantly decreased in the educated group compared to the others. Thus, it appeared that structured educational intervention emphasizing self-management had the greatest impact on patient outcomes. Cowie et al. demonstrated in a prospective study that utilization of a peak-flow based action plan dramatically reduced emergency room visits for acute asthma (48). Adams and coworkers studied 293 patients prospectively, who had moderate or severe asthma. Hospital admissions over a period of 12 months were found to be significantly associated with not possessing a written asthma action plan and lower preferences for autonomy in asthma management decisions (49). Abramson et al. have presented the most convincing evidence supporting the use of asthma actions plans and intensive education in high-risk patients (50). In a case-control study, circumstances of 89 asthma deaths were compared with 322 patients presenting to hospitals with acute asthma. Cases of asthma death were significantly less likely than controls to use a peak flow meter. Furthermore, written action plans were associated with a 70% reduction in the risk of death. The authors concluded that widespread use of written asthma management plans could lead to reductions in asthma mortality.

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Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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