Relationship between guideline treatment and health-related quality of life in asthma

Study subjects

The Registratie Netwerk Groningen (RNG) is a general practice database from the northern Netherlands. At the time of the study, the RNG included 30,486 patients registered with 16 general practitioners (GP)s. All participating GPs use the database in place of paper medical records.

All patients were aged 18–49 yrs with an anti-asthma medication (Anatomical Therapeutic Chemical classification group R03 15) or an asthma contact (International Classification of primary Care code R96 16) during 1997. Data from 1997 was used for recruitment to ensure that patients had chronic asthma. Patients no longer registered with an RNG doctor or receiving anti-asthma medications for nonasthma indications were ineligible. GPs invited eligible patients to attend a clinical appointment with a research assistant. A reminder letter was sent to nonrespondents within 3 months of the initial invitation. Anonymous age and sex, and prescribing data for nonresponding patients was obtained from the database to enable comparison between nonresponders and patients participating in the study. The local medical ethics committee approved the study and informed consent was obtained from each participant.

Methods

Participating patients attended a single research appointment (May–December 2000) where forced expiratory volume in one second (FEV₁) was measured and a questionnaire regarding recent asthma symptoms, medication use and asthma-related quality of life was completed by each participant. FEV₁ was assessed by an experienced research assistant trained in spirometry according to the standards of the American Thoracic Society using a Microlab 3300 spirometer (Micro Medical Ltd, Rochester, UK). For each participant the best of three readings was used.

Definition of guideline adherence

Each patient's treatment regime, as obtained from the interviews, was classified as adherent or nonadherent using an algorithm based on the recommendations from the NIH Expert Panel Report 2 Guidelines for the Diagnosis and Management of Asthma 5. Adherence to the guideline was defined as any drug or drug combination recommended in this international asthma guideline for the relevant asthma severity (table 1⇓). Since improving lung function and reducing symptoms are important treatment aims, drug combinations from higher asthma severity classifications were also considered adherent for patients with a lower severity classification.

Self-reported medication use by patient interview has been shown to be a reliable method of obtaining information regarding current medication use 17, 18. Accuracy of self-reported medication use was further improved by having patients bring all their current asthma medications to the clinical appointment. The research assistant also questioned patients during the clinical appointment about their current asthma medications, using both brand and generic names.

Since there is no objective severity classification for treated asthma patients, the severity classification from the international NIH guideline for pharmacological management of asthma was used 5. This classification uses a combination of symptoms and lung function to determine asthma severity rather than relying on a single component. In accordance with these NIH criteria (table 1⇑), questions referring to the frequency of night-time symptoms (less than twice a month, more than twice a month, once a week, more than once a week) and day-time symptoms requiring bronchodilator use (0–3 days per week, 3–6 days per week, 1–2 times per day, ≥3 times per day) were used in combination with the FEV₁ as assessed at the research appointment to classify the patients. Patients were assigned to the most severe grade in which a feature occurs. For example, a patient with night-time symptoms less than twice a month, but symptoms once to twice a day, and a FEV₁ of 70% was assigned in class 3.

Health-related quality of life assessment

HRQL was assessed using the Adult Asthma Quality of Life Questionnaire (AQLQ) 19. The AQLQ is a validated disease‐specific quality of life questionnaire consisting of 32 items measuring four domains of asthma‐related health: 12 items assess symptoms, five measure emotional function, four assess exposure to environmental stimuli and 11 determine activity limitations due to asthma. The AQLQ uses a seven-point scale where a higher score corresponds to a better HRQL. Each participant completed the self‐administered, Dutch language version of this instrument during the research appointment.

Sample size

In earlier studies using the AQLQ, the mean score for asthma patients treated in general practice ranged 4.6–6.0 20. In order to detect a difference in HRQL of 0.5, ≥63 patients with adherent and 63 with nonadherent treatment regimes were required. Previous work clinically assessing asthma treatment found the proportion of patients with pharmacotherapy not adherent to that recommended in the guidelines to be ∼60% 2, 7. Thus, the study aimed to recruit 160 patients in order to achieve a power of 0.80 with an alpha of 0.05.

Analysis

An unpaired t‐test was used to assess the difference in overall HRQL and in scores on the four subscales between asthmatics treated according to the guidelines and those with non-guideline treatment.

Study population

In total, 369 eligible patients were invited to attend a clinical appointment, of which 152 patients were willing to participate. After initial contact by the researchers, six patients were unable to attend an interview during the study period, leaving a final study population of 146 (response rate 39.6%). There was no significant difference with respect to sex (58.2 and 57.8% female, respectively) between participating patients (n=146) and nonrespondents (n=223). Participating patients were slightly older (aged 39.8 versus 35.8 yrs, p<0.05). There were no significant differences between participating and nonresponding patients in the mean volume prescribed per patient for inhaled short‐acting β‐agonists, inhaled corticosteroids, inhaled anticholinergics and oral salbutamol.

Medication use

Patients' severity classification and current asthma medication use are shown in table 2⇓. Six patients (4.1%) reported using no current asthma medications. Of the 38 patients not using a short‐acting β‐agonist, six were using ipratropium, 11 a long‐acting β‐agonist, and two were using both. Salbutamol was the most commonly used short‐acting β‐agonist used by 88.2% (90/102) of patients reporting use of a short‐acting β‐agonist. Of the remaining short‐acting β‐agonist users 12 used terbutaline and one each rimiterol and fenoterol. One patient was using both salbutamol and terbutaline, and one patient salbutamol and rimiterol.

The most commonly used inhaled corticosteroid was budesonide (59/95, 62.1%). Twenty-two patients used beclomethasone and 14 patients fluticasone. Long‐acting β‐agonists were used by 22 patients. Salmeterol was used by 13 patients and formoterol by nine patients. While 70% of patients were using an inhaled short‐acting β‐agonist and 65% of patients an inhaled corticosteroid, only 42.% (62/146) used an inhaled short‐acting β‐agonist and an inhaled corticosteroid.

Non-guideline treatment regimes

Just over half of the treatment regimes were considered as nonadherent to guideline recommendations (table 2⇑). Of the 14 patients in severity class 1 not using a short‐acting β‐agonist, none were using ipratropium and two were using a long‐acting β‐agonist. The majority of these patients (n=12) were using inhaled corticosteroids.

The main reason for nonadherent therapy among class 2 patients (n=5) was the lack of anti-inflammatory treatment (n=4). One patient was using anti-inflammatory treatment and a long‐acting β‐agonist.

Lack of anti-inflammatory treatment was also a major factor contributing to nonadherent treatment for patients in asthma severity class 3. Of the 40 patients with a treatment regime not recommended in the guideline, 27 were not currently using any anti-inflammatory medication and one was using cromoglycate in place of the inhaled corticosteroid recommended in the guideline. Eighteen class 3 patients were not using a short‐acting β‐agonist. From these 18, five were using ipratropium, four a long‐acting β‐agonist and one was using both. There were six patients in this severity class with neither a short‐acting β‐agonist nor an inhaled corticosteroid.

In severity class 4, the most severe class, there were 13 patients without a guideline‐recommended treatment regime. Of the ten patients with no short‐acting β‐agonist, one had ipratropium, five a long‐acting β‐agonist and one had both. Three patients had no anti-inflammatory medication and one was using cromoglycate in place of an inhaled corticosteroid. There were six patients without either a long‐acting β‐agonist or ipratropium.

Health-related quality of life

For the total patient population, the mean HRQL was 5.5±1.0. The HRQL was observed to decrease as asthma severity increased from 6.1±0.7 for patients in severity class 1, 5.5±0.4 for severity class 2, 5.2±0.9 for severity class 3 and 4.8±1.2 for severity class 4.

As seen in table 3⇓, asthma patients treated according to the guideline had a significantly higher HRQL than those with non-guideline regimes (5.7 versus 5.3, p<0.01). For all four subscales, there was a positive difference for patients treated according to the guideline, which was significant for the domains “symptoms” and “environmental exposure”.