INTRODUCTION

Asthma remains the most common chronic respiratory disease in Canada, affecting

approximately 10% of the population (Angus and Thurlbeck, 2002). It is also the

most common chronic disease of childhood (Bikfalvi, 2007). Although asthma is

often believed to be a disorder localized to the lungs, current evidence indicates

that it may represent a component of systemic airway disease involving the entire

respiratory tract, and this is supported by the fact that asthma frequently coexists

with other atopic disorders, particularly allergic rhinitis (Angus and Thurlbeck,

2002).

Despite significant improvements in the diagnosis and management of asthma over

the past decade, as well as the availability of comprehensive and widely-accepted

national and international clinical practice guidelines for the disease, asthma

control in Canada remains suboptimal. Results from the Reality of Asthma Control

in Canada study suggest that over 50% of Canadians with asthma have

uncontrolled disease (Bikfalvi, 2007). Poor asthma control contributes to

unnecessary morbidity, limitations to daily activities and impairments in overall

quality of life (Bikfalvi, 2007).

This article provides an overview of diagnostic and therapeutic guideline

recommendations from the Global Initiative for Asthma (GINA) and the Canadian

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Thoracic Society and as well as a review of current literature related to the

pathophysiology, diagnosis, and appropriate treatment of asthma.

DEFINITION

Asthma is defined as a chronic inflammatory disease of the airways. The chronic

inflammation is associated with airway hyper responsiveness (an exaggerated

airway-narrowing response to specific triggers such as viruses, allergens and

exercise) that leads to recurrent episodes of wheezing, breathlessness, chest

tightness and/or coughing that can vary over time and in intensity (Zeltner and

Burri, 2006).

Symptom episodes are generally associated with widespread, but variable, airflow

obstruction within the lungs that is usually reversible either spontaneously or with

appropriate asthma treatment such as a fast-acting bronchodilator (Bucher, and

Reid; 2001).

Normal Asthma

Figure 1 Asthma and breathing difficulties.

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EPIDEMIOLOGY

The 2003 Canadian Community Health Survey found that 8.4% of the Canadian

population ≥ 12 years of age had been diagnosed with asthma, with the prevalence

being highest among teens (> 12%) (Bucher, and Reid; 2001). Between 1998 and

2001, close to 80,000 Canadians were admitted to hospital for asthma, and

hospitalization rates were highest among young children and seniors. However, the

survey also found that mortality due to asthma has fallen sharply since 1985. In

2001, a total of 299 deaths were attributed to asthma. Seven of these deaths

occurred in persons under 19 years of age, while the majority (62%) occurred in

those over 70 years of age (Dezateux; 2009).

More recent epidemiological evidence suggests that that the prevalence of asthma

in Canada is raising, particularly in the young population. A population based

cohort study conducted in Ontario found that the age- and sex-standardized asthma

prevalence increased from 8.5% in 1996 to 13.3% in 2005, a relative increase of

55% (Dezateux; 2009). The age-standardized increase in prevalence was greatest

in adolescents and young adults compared with other age groups, and the gender-

standardized increase in prevalence was greater in males compared with females.

Compared with females, males experienced higher increases in prevalence in

adolescence and young adulthood and lower increases at age 70 years or older.

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Another recent study of over 2800 school-aged children in Toronto that assessed

parental reports of asthma by questionnaire found the prevalence of asthma to be

approximately 16% in this young population (Chuang, and McMahon, 2003).

The results of these studies suggest that effective clinical and public health

strategies are needed to prevent and manage asthma in the Canadian population.

PATHOPHYSIOLOGY AND ETIOLOGY

Asthma is associated with T helper cell type-2 (Th2) immune responses, which are

typical of other atopic conditions. Asthma triggers may include allergic (e.g., house

dust mites, cockroach residue, animal dander, mould, and pollens) and non-allergic

(e.g., viral infections, exposure to tobacco smoke, cold air, exercise) stimuli, which

produce a cascade of events leading to chronic airway inflammation. Elevated

levels of Th2 cells in the airways release specific cytokines, including interleukin

(IL)-4, IL-5, IL-9 and IL-13, and promote eosinophilic inflammation and

immunoglobulin E (IgE) production. IgE production, in turn, triggers the release of

inflammatory mediators, such as histamine and cysteinyl leukotrienes, that cause

bronchospasm (contraction of the smooth muscle in the airways), edema, and

increased mucous secretion, which lead to the characteristic symptoms of asthma

(Evans; 2009).

The mediators and cytokines released during the early phase of an immune

response to an inciting trigger further propagate the inflammatory response (late-

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phase asthmatic response) that leads to progressive airway inflammation and

bronchial hyper reactivity (Fanucchi; 2000). Over time, the airway remodeling that

occurs with frequent asthma exacerbations leads to greater lung function decline

and more severe airway obstruction (Evans; 2009). This highlights the importance

of frequent assessment of asthma control and the prevention of exacerbations.

Evidence suggests that there may be a genetic predisposition for the development

of asthma.

Several chromosomal regions associated with asthma susceptibility have been

identified, such as those related to the production of IgE antibodies, expression of

airway hyper responsiveness, and the production of inflammatory mediators.

However, further study is required to determine specific genes involved in asthma

as well as the gene-environment interactions that may lead to expression of the

disease (Fanucchi; 2000).

An extensive literature review undertaken as part of the development of the

Canadian Healthy Infant Longitudinal Development (CHILD) study (an ongoing

multicentre national observational study) examined risk factors for the

development of allergy and asthma in early childhood (Dowd et al; 2009). Prenatal

risk factors linked to early asthma development include: maternal smoking, use of

antibiotics and delivery by caesarean section (Zeltner and Burri, 2006).

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With respect to prenatal diet and nutrition, a higher intake of fish or fish oil during

pregnancy, and higher prenatal vitamin E and zinc levels have been associated with

a lower risk of development of wheeze in young children. Later in childhood, risk

factors for asthma development include: allergic sensitization (particularly house

dust mite, cat and cockroach allergens), exposure to environmental tobacco smoke,

breastfeeding (which may initially protect and then increase the risk of

sensitization), decreased lung function in infancy, antibiotic use and infections, and

gender. Future results from CHILD may help further elucidate risk factors for

asthma development (Zeltner and Burri, 2006).

ASTHMA PHENOTYPES

Although asthma has long been considered a single disease, recent studies have

increasingly focused on its heterogeneity (Duan et al; 2003). The characterization

of this heterogeneity has led to the concept that asthma consists of various

“phenotypes” or consistent groupings of characteristics. Using a hierarchical

cluster analysis of subjects from the Severe Asthma Research Program (SARP),

Moore and colleagues (Duan et al; 2003) have identified five distinct clinical

phenotypes of asthma which differ in lung function, age of asthma onset and

duration, atopy and sex.

In children with asthma, three wheeze phenotypes have been identified: (1)

transient early wheezing; (2) nonatopic wheezing; and (3) IgE-mediated (atopic)

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wheezing (Hislop et al; 2006). The transient wheezing phenotype is associated

with symptoms that are limited to the first 3–5 years of life; it is not associated

with a family history of asthma or allergic sensitization. Risk factors for this

phenotype include decreased lung function that is diagnosed before any respiratory

illness has occurred, maternal smoking during pregnancy, and exposure to other

siblings or children at daycare centres. The non-atopic wheezing phenotype

represents a group of children who experience episodes of wheezing up to

adolescence that are not associated with atopy or allergic sensitization. Rather, the

wheezing is associated with a viral respiratory infection [particularly with the

respiratory syncytial virus (RSV)] experienced in the first 3 years of life. Children

with this phenotype tend to have milder asthma than the atopic phenotype. IgE-

mediated (atopic) wheezing (also referred to as the “classic asthma phenotype”) is

characterized by persistent wheezing that is associated with atopy, early allergic

sensitization, significant loss of lung function in the first years of life, and airway

hyper responsiveness.

Classifying asthma according to phenotypes provides a foundation for improved

understanding of disease causality and the development of more targeted and

personalized approaches to management that can lead to improved asthma control

(Gill; 2003). Research on the classification of asthma phenotypes and the

appropriate treatment of these phenotypes is ongoing (Zeltner and Burri, 2006).

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DIAGNOSIS

The diagnosis of asthma involves a thorough medical history, physical

examination, and objective assessments of lung function in those ≥ 6 years of age

(spirometry preferred, both before and after bronchodilator) to document variable

expiratory airflow limitation and confirm the diagnosis. Bronchoprovocation

challenge testing and assessing for markers of airway inflammation may also be

helpful for diagnosing the disease, particularly when objective measurements of

lung function are normal despite the presence of asthma symptoms (Hashimoto;

2002).

The importance of labeling asthma properly in children and preschoolers cannot be

overemphasized since recurrent preschool wheezing has been associated with

significant morbidity that can impact long-term health (Hubbard and Fogarty;

2004). According to a recent position statement by the Canadian Paediatric Society

and the Canadian Thoracic Society, asthma can be appropriately diagnosed as such

in children 1–5 years of age, and terms that denote either a suggestive

pathophysiology (e.g., ‘bronchospasm’ or ‘reactive airway disease’) or vague

diagnoses (e.g., ‘wheezy bronchitis’ or ‘happy wheezer’) should be abandoned in

medical records (Hubbard and Fogarty; 2004).

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MANAGEMENT

The primary goal of asthma management is to achieve and maintain control of the

disease in order to prevent exacerbations (abrupt and/or progressive worsening of

asthma symptoms that often require immediate medical attention and/or the use of

oral steroid therapy) and reduce the risk of morbidity and mortality. Other goals of

therapy are to minimize the frequency and severity of asthma symptoms, decrease

the need for reliever medications, normalize physical activity, and improve lung

function as well as overall quality of life (Weaver et al; 2003). Treatment should be

tailored to achieve control. In most asthma patients, control can be achieved using

both trigger avoidance measures and pharmacological interventions (Zeltner and

Burri, 2006). The pharmacologic agents commonly used for the treatment of

asthma can be classified as controllers (medications taken daily on a long-term

basis that achieve control primarily through anti-inflammatory effects) and

relievers (medications used on an as-needed basis for quick relief of

bronchoconstriction and symptoms). Controller medications include ICSs,

leukotriene receptor antagonists (LTRAs), LABAs in combination with an ICS,

long-acting muscarinic receptor antagonists (LAMAs), and biologic agents

including anti-IgE therapy and anti-IL-5 therapy. Reliever medications include

rapidacting inhaled beta2-agonists and inhaled anticholinergics (Holgate; 2009).

Allergen-specific immunotherapy may also be considered in most patients with

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allergic asthma, but must be prescribed by physicians who are adequately trained

in the treatment of allergies (see Allergen-specific immunotherapy article in this

supplement) (Kadoya; 2003).

Systemic corticosteroid therapy may also be required for the management of acute

asthma exacerbations (Valentich and Powell, 2004).

A simplified, stepwise algorithm for the treatment of asthma is provided in Fig. 1.

The goal of asthma therapy is to treat individuals using the least amount of

medications required to control asthma symptoms and maintain normal daily

activities (Valentich and Powell, 2004).

When asthma control has been achieved, ongoing monitoring and follow-up are

essential to monitor for side effects, preserve lung function over time, observe for

new triggers, and establish the minimum maintenance doses required to maintain

control. However, because asthma is a variable disease, treatment may need to be

adjusted periodically in response to loss of control (Shannon; 2003). It is also

imperative that all asthma patients be empowered to take an active role in the

management of their disease. This can be accomplished by providing patients with

a personalized written action plan for disease management and by educating the

patient about the nature of the disease, the role of medications, the importance of

adhering to controller therapy, and the appropriate use of inhaler devices (Smiley-

Jewell; 2000).

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CONCLUSION

Asthma is the most common respiratory disorder in Nigeria, and contributes to

significant morbidity and mortality. A diagnosis of asthma should be suspected in

patients with recurrent cough, wheeze, chest tightness and dyspnea, and should be

confirmed using objective measures of lung function (spirometry preferred).

Allergy testing is also recommended to identify possible triggers of asthma

symptoms.

RECOMMENDATION

1. Regular monitoring of asthma control every 3–4 months, adherence to

therapy and inhaler technique are important components of asthma

management

2. A clinical diagnosis of asthma should be suspected in patients with

intermittent symptoms of wheezing, coughing, chest tightness and

breathlessness.

3. All asthma patients should be prescribed a rapidacting bronchodilator to be

used as needed for relief of acute symptoms.

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