Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICS) represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonist inhalers are preferred for most adults who fail to achieve control with ICS therapy. Biologic therapies targeting immunoglobulin E or interleukin-5 are recent additions to the asthma treatment armamentarium and may be useful in select cases of difficult to control asthma. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma, but should only be prescribed by physicians with appropriate training in allergy. In addition to avoidance measures and pharmacotherapy, essential components of asthma management include: regular monitoring of asthma control using objective testing measures such as spirometry, whenever feasible; creation of written asthma action plans; assessing barriers to treatment and adherence to therapy; and reviewing inhaler device technique. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma in adults and children.Asthma disease paper.
Background
Asthma remains the most common chronic respiratory disease in Canada, affecting approximately 10% of the population [1]. It is also the most common chronic disease of childhood [2]. 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 [3].
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 [4]. Poor asthma control contributes to unnecessary morbidity, limitations to daily activities and impairments in overall quality of life [1].
This article provides an overview of diagnostic and therapeutic guideline recommendations from the Global Initiative for Asthma (GINA) and the Canadian Thoracic Society and as well as a review of current literature related to the pathophysiology, diagnosis, and appropriate treatment of asthma.
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Definition
Asthma is defined as a chronic inflammatory disease of the airways. The chronic inflammation is associated with airway hyperresponsiveness (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. 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 [5].
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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%) [6]. Asthma disease paper.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 [6].
More recent epidemiological evidence suggests that that the prevalence of asthma in Canada is rising, 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% [7]. 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.
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 [8]. The results of these studies suggest that effective clinical and public health strategies are needed to prevent and manage asthma in the Canadian population.
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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 [5, 9].
The mediators and cytokines released during the early phase of an immune response to an inciting trigger further propagate the inflammatory response (late-phase asthmatic response) that leads to progressive airway inflammation and bronchial hyperreactivity [9]. Over time, the airway remodeling that occurs with frequent asthma exacerbations leads to greater lung function decline and more severe airway obstruction [10]. This highlights the importance of frequent assessment of asthma control and the prevention of exacerbations. Asthma disease paper.
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 hyperresponsiveness, 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 [5, 9].
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 [11]. Prenatal risk factors linked to early asthma development include: maternal smoking, use of antibiotics and delivery by caesarean section. 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.
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Asthma phenotypes
Although asthma has long been considered a single disease, recent studies have increasingly focused on its heterogeneity [12]. 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 [13] 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) non-atopic wheezing; and (3) IgE-mediated (atopic) wheezing [14]. 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. Asthma disease paper.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 hyperresponsiveness.
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 [13]. Research on the classification of asthma phenotypes and the appropriate treatment of these phenotypes is ongoing.
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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 (see Table 1). 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 [5, 15, 16].
Table 1
Diagnosis of asthma based on medical history, physical examination and objective measurements [5, 15, 16]
| Medical history |
• Assess for classic symptoms of asthma:
− Wheezing
− Breathlessness
− Chest tightness
− Cough (with our without sputum)
• Assess for symptom patterns suggestive of asthma:
− Recurrent/episodic
− Occur/worsen at night or early in the morning
− Occur/worsen upon exposure to allergens (e.g., animal dander, pollen, dust mites) or irritants (e.g., exercise, cold air, tobacco smoke, infections)
− Respond to appropriate asthma therapy
• Assess for family or personal history of atopic disease (particularly allergic rhinitis) |
Physical examination
• Examine for wheezing on auscultation
• Examine upper respiratory tract and skin for signs of other atopic conditions |
Objective measures for confirming variable expiratory airflow limitation (spirometry preferred)
• Documented airflow limitation:
▪ Diagnostic criteria: at least once during diagnostic process when FEV1 is low, confirm that FEV1/FVC is reduced (normally > 0.75–0.80 in adults, > 0.90 in children) Asthma disease paper. |
|
AND |
| • Documented excessive variability in lung function using one or more of the tests below (the greater the variations, or the more occasions excess variation is seen, the more confident the diagnosis): |
|
Diagnostic criteria |
| ▪ Positive bronchodilator (BD) reversibility testa (more likely to be positive if BD is withheld before test: SABA ≥ 4 h, LABA ≥ 15 h) |
→ Adults increase in FEV1 of > 12% and > 200 mL from baseline, 10–15 min after 200–400 μg albuterol or equivalent (greater confidence if increase is > 15% and > 400 mL)
→ Children increase in FEV1 of > 12% predicted |
| ▪ Excessive variability in twice-daily PEF over 2 weeksa |
→ Adults average daily diurnal PEF variability > 10%b
→ Children average daily diurnal PEF variability > 13%b |
| ▪ Significant increase in lung function after 4 weeks of anti-inflammatory treatment |
→ Adults increase in FEV1 by > 12% and > 200 mL (or PEFc by > 20%) from baseline after 4 weeks of treatment, outside respiratory infections |
| ▪ Positive exercise challenge testa |
→ Adults fall in FEV1 of > 10% and > 200 mL from baseline
→ Children fall in FEV1 of > 12% predicted, or PEF > 15% |
| ▪ Positive bronchial challenge test (usually only performed in adults) |
→ Fall in FEV1 from baseline of ≥ 20% with standard doses of methacholine or histamine, or ≥ 15% with standardized hyperventilation, hypertonic saline or mannitol challenge |
| ▪ Excessive variation in lung function between visits (less reliable)a |
→ Adults variation in FEV1 of > 12% and > 200 mL between visits, outside of respiratory infections
→ Children variation in FEV1 of > 12% or > 15% in PEFc between visits (may include respiratory infections) |
Allergy testing
• Perform skin tests to assess allergic status and identify possible triggers |
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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 [17].Asthma disease paper. 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 [17].
Medical history
Important questions to ask when taking the medical history of patients with suspected asthma are summarized in Table 2. The diagnosis of asthma should be suspected in patients with recurrent cough, wheeze, chest tightness and/or shortness of breath. Symptoms that are variable, occur upon exposure to triggers such as allergens or irritants, that often worsen at night and that respond to appropriate asthma therapy are strongly suggestive of asthma [5, 16]. Alternative causes of suspected asthma symptoms should be excluded (see “Differential diagnosis” section in this article).
Table 2
Key questions to ask when taking the medical history of patients with suspected asthma
| • Asthma symptoms (cough, wheeze, increased work of breathing)? |
| • Age of onset of symptoms? |
| • Timing of symptoms (day vs. night)? |
| • Is there a seasonal component to the worsening of symptoms? |
| • Possible triggers (viral infections, animal exposures, pollens, tobacco smoke, emotion)? |
| • Severity of symptoms (often reflected by unscheduled physician appointments at a walk-in clinic or emergency room, hospital admissions, and need for rescue oral corticosteroids)? |
| • Past investigations including chest X-rays, spirometry, allergy testing, sweat chloride testing? |
| • Other co-morbidities (e.g., food allergy, venom allergy)? |
| • Current and past treatments? Duration of use? Reasons for discontinuation? |
| • Barriers to treatment (cost of medication, proximity to health care providers)? |
| • Exposure to second- and third-hand (i.e., the lingering smell of tobacco smoke on clothing or in vehicles) tobacco smoke? |
| • Presence of household pets? |
| • Impact of the symptoms on the patient/family quality of life (missed time from activities, school or work due to asthma symptoms)? |
A positive family history of asthma or other atopic diseases and/or a personal history of atopic disorders, particularly allergic rhinitis, can also be helpful in identifying patients with asthma. During the history, it is also important to enquire for possible triggers of asthma symptoms, such as cockroaches, animal dander, moulds, pollens, exercise, and exposure to tobacco smoke or cold air. When possible, objective testing for these triggers should be performed. Exposure to agents encountered in the work environment can also cause asthma. If work-related asthma is suspected, details of work exposures and improvements in asthma symptoms during holidays should be explored. It is also important to assess for comorbidities that can aggravate asthma symptoms, such as allergic rhinitis, sinusitis, obstructive sleep apnea and gastroesophageal reflux disease [16].
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The diagnosis of asthma in children is often more difficult since episodic wheezing and cough are commonly associated with viral infections, and children can be asymptomatic with normal physical examinations between exacerbations. In addition, spirometry is often unreliable in patients under 6 years of age, although it can be performed in some children as young as 5 years. A useful method of confirming the diagnosis in young children is a trial of treatment (8–12 weeks of a daily ICS and a short-acting bronchodilator as needed for rescue medication). Asthma disease paper.Marked clinical improvement during the treatment period, as reflected by a reduction in daytime or nocturnal symptoms of asthma, a reduction in the use of rescue bronchodilator medication, absence of acute care visits (e.g., same-day physician appointments or emergency room visits) and hospitalizations for asthma exacerbations, and the absence of rescue oral corticosteroids are all indicators that the daily ICS therapy is working and that a diagnosis of asthma is likely [5, 18, 19]. In a young child who is symptomatic with cough, wheeze, or increased difficulty breathing, a physical examination both before and after administration of a bronchodilator is of extreme value and can be used as a diagnostic tool. If the respiratory symptoms resolve within 10–15 min of bronchodilator administration, a diagnosis of asthma may be established by a physician or other healthcare provider.
The modified Asthma Predictive Index (mAPI) is a useful tool for identifying young children with recurrent wheeze who may be at high risk of developing asthma (see Table 3; also available online at: https://www.mdcalc.com/modified-asthma-predictive-index-mapi). A positive mAPI in the preschool years has been found to be highly predictive of future school-age asthma [20]. Asthma disease paper.
