Clinical, economic, and humanistic burden of asthma in Canada: a systematic review

Of the 30 studies on clinical burden, 1 was a case–control, 22 were cohort, and 7 were cross-sectional studies. Characteristics of studies reporting on clinical burden are shown in Table 3.

Most studies clearly reported the study design (97%), setting (100%), participants (87%), and statistical methods employed (70%). However, less than half reported on potential sources of bias and confounding factors or how missing data was handled. Furthermore, less than half of the studies reported on how loss to follow-up was addressed in both the methods and results sections, or how sensitivity analyses were conducted. Main results for outcomes data were appropriately reported in 97 % of the clinical burden studies, and more than 90% met the STROBE criteria for appropriate quality discussion. Most (77%) gave the source of study funding and the roles of the funders. (Tables 1 and 2).

Studies employed a variety of definitions for asthma, including ICD codes, physician visits and/or hospitalizations for asthma (based on billing codes), asthma medication prescriptions filled, and patient self-report. We report the definitions used, but these definitions were not reconciled in this review. When asthma was defined by the presence of ICD codes, it was considered to be narrowly defined, whereas a broad asthma definition included visits for an asthma-related diagnosis and asthma-related hospitalizations among the discharge diagnoses.

Table 4 provides an overview of hospitalization rates for adult and pediatric patients with asthma in Canada. Reported rates of hospitalization for asthma varied widely according to age, geographic region, gender, and asthma medication use. In a large cohort study spanning over 20 years, Suissa et al. [41] obtained data from the Saskatchewan Health databases on asthma patients from that province aged 5–44 between 1975 and 1991 and found that the overall rate of asthma hospitalization was 42 per 1000 asthma patients per year in patients with at least 1 year of follow-up. The rate was higher (48 per 1000) in patients receiving at least 3 anti-asthma medication prescriptions in any 1 year. During the variable follow-up period (up to 4 years), regular use of inhaled corticosteroids (ICS) was associated with a 31% reduction in the rate of hospital admissions for asthma and a 39% reduction in the rate of readmissions for the cohort with more severe asthma who had been previously hospitalized for the condition during the 1-year baseline period. The study investigators concluded that their findings emphasize the importance of regular use of inhaled corticosteroids to avoid hospitalizations.

In a retrospective cross-sectional study of asthma patients aged 5–54 years using health databases in Saskatchewan, Klomp et al. [36] found that, in 2002–03 and 2003–04, the hospitalization rate for asthma was 10.9 per 1000 patients per year.

Agha et al. [27], using data on hospital admissions from the Dischrage Abstract Database of the Canadian Institute for Health Information, reported 8,583 asthma hospitalizations among 255,284 pediatric patients (a rate of 33.6 in 1000 patients) born between 1993 and 2000 in Toronto.

A significantly lower rate was reported in Canada by Seung et al. [42], who cited figures reported by the Public Health Agency of Canada of 143 asthma-related hospitalizations per 100,000 adult and pediatric patients, or 1.43 in 1000, in 1998 (with an additional 3.7 per 1000, many of whom had underlying asthma, hospitalized for influenza/pneumonia).

Higher rates were reported for hospital admissions of patients who initially presented to the emergency department (ED). Lougheed et al. [28] reported that 6.9% of adults and 10.8% of children who presented to the ED with asthma were admitted to the hospital.

According to the results of a study based on interviews with parents, 25% of the pediatric study population (124 of 490 patients) had been hospitalized for asthma in the previous 12 months [21]. In a large study utilizing data from Quebec administrative databases, children aged 5 to 15 years with at least 1 exacerbation in the year prior to treatment initiation with ICS or leukotriene receptor antagonists (LTRA) had higher rates of hospitalizations than those with no exacerbation in the previous year (0.03 vs. 0.005 hospitalizations per patient per year in the ICS group and 0.06 vs. 0.003 per patient per year in the LTRA group) [43]. The proportion of prescribed days covered was significantly higher in the LTRA group than in the ICS group (52% vs. 34%) [43].

In a study of all Ontario babies born during the year 1994 who were diagnosed with asthma before their sixth birthday, there was a decreasing trend in hospitalization rates with age, from 86.7 per 1000 patients per year in the 0 to 2 years age group to 27.3 per 1000 patients for those aged 3 to 5 years and 10.9 per 1000 for those aged 6 to 9 years. These investigators also found that children with persistent asthma had more than one and a half times higher hospitalization rates compared with patients whose asthma was in remission (63 per 1000 patients vs. 39 per 1000 patients per year) [26].

In another Ontario-based study that examined asthma seasonality and hospitalizations by gender and age group over a 12-year period, results of spectral analysis revealed that hospitalization rates for children with asthma were highest in September and October each year across the 12-year period, with a 2 to 3-times higher rate of hospitalizations in boys (180 per 100,000) than in girls under the age of 9 years [20]. However, among children older than 9 years, female hospitalizations exceeded those of males [20].

The large variations in reported rates of hospitalizations may be due to variations in ED visit rates and/or hospital admission percentages [28]. Hospital admissions appear to follow a bimodal age distribution pattern, with the very young and the elderly more likely to be admitted [28]. Other factors that can drive up rates of hospitalization in particular regions or among specific populations are higher disease prevalence, greater disease severity, multiple comorbidities, and barriers to care associated with socioeconomic status [27].

The number of asthma emergency visits varied by age, type of treatment, social status, and living area (urban/non-urban). Table 5 summarizes ranges and mean numbers of annual ED visits for asthma, as reported in the included studies. According to several studies, both children and adults with asthma averaged less than 1 ED visit per patient per year [21, 23, 28]. ED visit rates were significantly higher in women than in men and, overall, the rate of ED visits increased with age [28].

In a study investigating the impact of appropriate use (according to the 1999 Canadian asthma consensus report and the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma) and compliance with asthma medications in adults, the rate of ED visits for asthma was twice as high for patients not using asthma medication appropriately (high-dose SABA plus low-dose ICS) than for those using it appropriately (low-dose SABA plus high-dose ICS) [38].

Rosychuk et al. [19] examined trends in asthma-related ED visits by more than 45,000 children aged <18 years during the period from April 1999 to March 2005 and did not observe decreased ED presentation rates over time, despite improvements in treatment and availability of guidelines. The standardized rates remained stable over time, with 21.1 visits occurring per 1000 patients in 1999/2000 versus 19.8 per 1000 in 2004/2005.

Sin et al. [30, 44] reported that elderly asthmatic patients using ICS post-discharge from hospital were 29% less likely to be readmitted to hospital for asthma and 39% less likely to experience all-cause mortality compared with those who did not receive ICS post-discharge over a 1-year follow-up period. When age, sex, comorbidity, and use of other antiasthma medications were controlled for, ICS use was associated with a 32% relative rate reduction for recurrent hospitalization or all-cause mortality (95% CI 23%-39%). Among patients who received at least 1 prescription for ICS within 1 year prior to the index hospitalization, the use of ICS 90 days post-discharge was associated with a 41% decrease in recurrent asthma-related hospitalizations or deaths compared with non-use of ICS (95% CI 32%-49%).

Sin et al. [32] also reported on ED visits in children born in Alberta between 1985 and 1988, stratified by SES, and found that very poor children were 23% more likely to have had an ED visit for asthma compared with children from non-poor families (RR 1.23; 95% CI 1.14 – 1.33). Very poor children had a similar risk of having an asthma-related ED visit as poor children (RR 0.97; 95% CI 0.91 – 1.04).

Studies that reported rates of asthma-related physician visits are summarized in Table 6. In a population-based study evaluating 14-year trends in Manitoba in utilization of physician resources for asthma, Dik et al. [29] found that, between the period 1985–1988 and 1994–1998, the greatest increases in prevalence and incidence of physician visits for asthma occurred in the youngest age groups, while in adults the prevalence and incidence changed little with time. However, the average rate of physician visits for asthma decreased from 1.66 visits per patient-year in 1985–1988 to 1.40 in 1989–1993, and further to 1.16 visits per patient-year in 1994–1998.

More former or current smokers than non-smokers visited their physician [35], as did patients with work-related asthma vs. non-work-related asthma [25] and patients inappropriately using their asthma medication [38]. Among elderly patients, the rate of physician visits for asthma was not influenced by treatment with ICS [44].

Children in an Ontario-based study who were born in 1994 and diagnosed with asthma before age 6, and whose asthma persisted until age 11 (as determined by the presence of claims for physician and/or hospital visits between the ages of 6 and 11), had a higher rate of physician visits than those in remission (60 vs. 46.9 visits per 100 patients per year) [26].

Lynd et al. [40] reported that 27% of patients receive oral corticosteroids, 17% use no ICS, 47% receive less than 4 ICS canisters per year, 29% use 5 to 12 canisters, and 8% use more than 12 ICS canisters per year.

Based on available data, children received more prescriptions per patient per year than adults [11, 21, 38]. Patients with inappropriate use of asthma medications (ie, those who were non-adherent to guidelines recommended in the 1999 Canadian asthma consensus report and the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma) received more than double the number of prescriptions per patient per year (mean [SD] 7.5 [4.9]) compared with those who used asthma medication appropriately (mean [SD] 3.3 [1.9]) [38].

Ten studies evaluated the economic burden of asthma in Canada (5 cohort studies, 4 cross-sectional, and 1 economic analysis). Costs in the economic analysis were calculated for 1,350,871 persons, based on the 1998/1999 estimate that 57% of 2,389,085 persons aged ≥4 years had uncontrolled asthma.

More than 80% of these studies met the STROBE criteria for appropriate quality discussion. Most studies clearly reported the study design (90%), setting (100%), participants (90%), and statistical methods employed (70%). However, less than half reported on potential sources of bias and confounding factors or how missing data was handled and how loss to follow-up was addressed in both the methods and results sections or sensitivity analyses conducted. Most studies (60%) gave the source of funding and the role of the funders for their study (Table 1).

Asthma cases were identified using ICD codes or clearly stated diagnosis, retrospective physician visits, hospitalizations for asthma, and/or asthma medication prescriptions filled or patient self-report of asthma diagnosis or symptoms. There was available evidence on both the direct and indirect components of the economic burden of asthma in Canada. The overall burden varied based on whether studies reported costs from the perspective of an individual patient with asthma or costs at the population level. Few Canadian studies reported a cost per episode of acute asthma, and no studies reported the cost per patients overall. Five studies reported data on the direct costs of asthma at the patient-level. Three of these studies reported asthma costs per asthma patient [10, 24, 37], while 2 studies reported asthma costs per acute asthma episode [34, 42]. Three studies reported population-level direct costs for asthma [10, 24, 42]. Study characteristics are presented in Table 7.

Based on data from administrative databases in British Columbia, average total annual direct cost estimates in the general population ranged from $366.17 to $490.88 per asthma patient (Table 8) [10].

Ungar and colleagues [33] estimated the total cost of asthma in children aged 0–14 years in Ontario to be $883.48 per child from the healthcare perspective (Table 8). Adjusted annual societal costs per patient (1995 Canadian dollars) ranged from $1,122 in children aged 4–14 years to $1,386 in children younger than 4 years. From the Ministry of Health perspective, adjusted annual costs per patient were $663 in children over 4 years and $904 in younger children. Adjusted annual costs from the patient perspective were $132 in children over 4 years and $129 in children under 4 years.

During the period from 1996 – 2000, average hospitalization costs ranged from $67.90 to $136.87 per patient per year in the general population in British Columbia (aged 5 to 55 years), depending on the definition used to categorize asthma-related hospitalizations [10]. The estimated average annual hospitalization cost for asthma in children was $682.21 per patient in Ontario [33].

Sadatsafavi et al. [10] reported that ED visits made by asthma patients in the general population could cost the healthcare system anywhere between $66.35 and $122.09 per visit, depending on the asthma definition used. The reported range of average costs for ED visit per acute asthma episode was $209.48 to $274.48 [10, 33]. Ungar and colleagues [33] estimated the average annual cost for ED visits in children to be $15.68.

The average costs for physician visits per acute asthma episode were estimated to range from $31.72 [34] in an economic modeling study using prospectively collected resource utilization data (9/1/94 to 8/31/95) from hospital emergency department visitors to $31.91 in the economic analysis by Seung and Mittmann [42]. Average costs of $98.02 and $70.57 annually per pediatric patient were reported for family physician and specialist visits, respectively, in the prospective study by Ungar et al. [33]. Although the cost per respiratory specialist visit was higher than the cost per family physician visit ($105.40 vs. $51.40 for the first visit and $23.10 vs. $16.25 for an additional visit), nearly twice as many patients (271, or 80%) reported visiting a family physician, at an average annual use of 3.6, compared with a respiratory specialist (141, or 42% of patients), at an average annual use of 2.1 [33]. A study conducted in Ontario demonstrated that outpatient claim costs for persons with asthma exceeded those for persons without asthma by about $200 per person per year [2].

With regard to asthma medication prescriptions, the administrative database study from British Columbia estimated the average annual cost for asthma medication in the general population to be $231.92 per patient [10]. Ungar et al. [33] estimated the average annual costs for medication per patient in children to be $352.87 from the societal perspective and $86.26 (2011 $CAD) from the patient perspective. Estimated average medication costs per acute asthma episode ranged from $5.29 to $629.39 in these studies [10, 33].

The 1998–1999 healthcare cost for asthmatic children in Ontario ($120 million, or $227.1 - $640.3 per child per year, depending on age group) was considerably higher than the total asthma cost for the general population (all ages) of British Columbia during the period 1996 – 2000 (~$41.8 million, or $331 per patient per year) (Table 9) [10, 24].

Based on data from administrative healthcare databases (April 1996 through March 2000), the total annual population-level asthma cost estimates in the general population in British Columbia ranged from ~ $46.3 million to $62.0 million , depending on the definition of asthma used [10]. Between ~8.5 million and ~17.2 million of that was spent on asthma-related hospitalizations, ~8.4 million to ~15.5 million on physician/ED visits, and ~15.4 million to ~29.3 million on asthma medications [10]. Medication costs represented the bulk (63.9%) of the total cost, hospitalizations/ED visits comprised 17.8%, and physician visits accounted for 18.3% of the total cost.

In Ontario, the total population-level costs for asthma in children aged 0–9 years ranged from ~ $140 million during 1994–1995 to ~ $120 million in 1998–1999 [24].

About 50% of children missed 1–3 days of school (47.6% in the group with low-severity asthma, 53.9% in those with moderate severity, and 50.6% in the severe asthma group), and 5.7% of the low severity, 5.3% of the moderate severity, and 9.1% of the severe asthma patients were absent for 7 or more days [47].

Malo et al. [46] evaluated a random sample of 8 to 10 accepted claims for occupational asthma per year from 1988 to 2002 in Quebec and found that the mean cost of compensation for loss of income (CLI) across the 15 years (not accounting for inflation) was $72,500 (median $40,700) and the mean cost of compensation for functional impairment (CFI) was $11,700 (median $7,600). Median CLI costs were significantly higher in men than women (69.9 vs 13.1), in workers aged ≥40 years versus those <40 years (90.1 vs 27.4), and in workers taking inhaled steroids at diagnosis (92 vs 52) and at reassessment (81 vs 35). Median CFI costs were significantly higher for individuals being treated with inhaled steroids at the time of diagnosis (14.0 vs 5.2) and reassessment (13 vs 6).

In a population of ~1.5 million working-age individuals in Alberta with an asthma prevalence of 8.5%, the number of asthma-related productivity lost work days ranged from 441,728 to 533,363 in 1 year, at a cost of $78.1 to $94.4 million in lost productivity [48].

Ungar et al. [49] reported productivity loss days (PLD) without reporting actual indirect costs. They found that annual PLD varied from 12 in employed persons to 20 in students, 22 in homemakers, retirees and the unemployed, and 49 in disability pensioners. Annual PLDs increased with increasing disease severity.

Fourteen articles reporting results from 13 studies were retained for inclusion out of the 309 studies identified by the humanistic burden literature search. Two were cohort studies, 8 were cross-sectional, and 4 studies were RCTs. Only 1 of these was a pediatric study [50], which assessed the impact of asthma medication on children using the 3-domain Pediatric Asthma Quality of Life Questionnaire (PAQLQ). No studies were identified that reported utilities or QoL from a caregiver perspective. QoL assessments focused on subgroups of the asthma population, and studies had small numbers of participants. A variety of definitions were used to define asthma including clinical diagnosis, presence of symptoms, and positive inhalation tests. Characteristics of studies reporting on humanistic burden are detailed in Table 10.

Overall, most studies on humanistic burden met good reporting quality standards in accordance with STROBE criteria (Table 1). However, less than half of the studies reported how missing data and loss to follow-up was handled or sensitivity or other analyses performed. Most studies also met the STROBE criteria for appropriate quality discussion (80%) and reported information on study funding (80%).

The effect of psychiatric disorders on asthma control and QoL in adults was examined in 2 studies [57, 58]. Another 2 studies examined QoL by asthma severity and chronicity [54, 62]. Eleven studies used the 32-item AQLQ to assess the impact of asthma on patients’ QoL [51‐56, 58‐63]. Other tools that were used to measure the humanistic burden of asthma were the AQL-5D, the EQ-5D, the SF-6D, the Health Utilities Index (HUI-3), the Asthma Control Questionnaire (ACQ), and the 8-question St Georges Respiratory Questionnaire (SGRQ).