Epidemiology
The global prevalence, morbidity, mortality, and economic burden attributable to asthma have progressively increased over the last several decades. About 300 million people worldwide currently have asthma and its prevalence increases by 50% every decade. Approximately 180,000 deaths annually are attributable to asthma worldwide. Most asthma deaths occur in those aged ≥45 years and are preventable. The number of disability-adjusted life years lost due to asthma worldwide is approximately 15 million per year, which is similar to that for diabetes.[2]
In the UK, 8 million people (adults and children) have been diagnosed with asthma (about 12% of the population). In 2012, 12,565 women per 100,000 and 12,033 men per 100,000 had asthma. In the UK, around 1200 people a year are recorded as dying from asthma. In 2012, the majority of asthma deaths were in women and in people aged over 65 years. Asthma accounts for 60,000 hospital admissions per year and many more patients will attend emergency departments without requiring admission.[3]
Exacerbations can affect people with asthma irrespective of age, ethnicity, or disease severity, and can occur frequently. People with infrequent symptoms (e.g., less than weekly, or only with strenuous exercise) comprise up to 30% of asthma exacerbations and deaths, and are over-represented in studies of severe and fatal exacerbations.[1]
Risk factors
Most common risk factor for exacerbations, with more than half of asthma exacerbations thought to be triggered by respiratory viruses.[11]
Rates of exacerbation mirror the seasonal nature of many respiratory viral infections.
Rhinovirus, respiratory syncytial virus, and influenza virus are frequently implicated as triggers.[7]
Mechanisms that lead to inflammation may be virus-specific. However, it is likely that most viruses infect epithelial cells. This infection triggers release of inflammatory mediators, which ultimately results in inflammatory cell recruitment (often neutrophilic), airway oedema, and mucus gland hypersecretion.[7]
High use of short-acting beta-2 agonists (e.g., average use greater than once daily) is an important risk factor for exacerbations (and is associated with increased risk of accident and emergency department visits or hospitalisations), with substantially increased mortality if one or more inhaler devices of salbutamol or equivalent is being used per month on average.[1][13][14][15] Risks are higher with the use of nebulised short-acting beta-2 agonists.[1]
Even in the shorter term, increasing use of a short-acting beta-2 agonist reliever is associated with greater risk of a severe exacerbation in the following days to weeks.[1]
Regular use of short-acting beta-2 agonists down-regulates beta-receptors and diminishes response to further short-acting beta-2 agonist treatment (thus resulting in further increases in use).[1]
High use of short-acting beta-2 agonists may be symptom-driven or habitual.[1]
Incorrect inhaler technique is a potentially modifiable risk factor for exacerbations, even if the patient has few asthma symptoms.[1] Poor inhaler technique (which is present in up to 70-80% of patients, most of whom are unaware of the issue) is associated with increased unscheduled use of healthcare resources and poor clinical control including increased risk of severe exacerbations.[1][16]
Current cigarette smoke exposure is a statistically significant modifiable risk factor for asthma exacerbations, even in patients with few asthma symptoms.[1][17] Cigarette smoke exacerbates asthma symptoms, accelerates long-term decline in lung function, and impairs short-term therapeutic response to corticosteroids.[19] Use of e-cigarettes/vapes is associated with increased risk of respiratory symptoms and asthma exacerbations.[20][21]
The ubiquitous and diverse nature of allergens often makes it difficult to identify all potential allergic triggers for a person.
Common allergens include cats, dogs, cockroaches, dust mites, pollen from trees, weeds, and grass, and fungal spores.
Occupational allergens are extremely diverse. Professions commonly affected include bakers, farmers, carpenters, and people involved in manufacturing plastics, foams, and glues.
Allergens are thought to provoke a Th-2-mediated immunoglobulin E response that ultimately leads to inflammation and increased mucus secretion, which exacerbates airway obstruction. The inflammatory response is often eosinophilic in nature. Interleukin (IL)-5 and IL-13 are important cytokines in the recruitment of eosinophils.[7]
Eosinophils release inflammatory mediators that also can result in further inflammation and epithelial cell injury.
Particulate matter linked to poor air quality and asthma exacerbations include carbon compounds, volatile organic compounds, nitrogen dioxide, sulfur dioxide, diesel exhaust emissions, endotoxins, and cigarette smoke.[22][23][24] There is specific evidence for exposure to particulate matter with diameter <2.5 micrometres (PM2.5) as a risk factor for acute asthma exacerbation in adults.[5]
Short-term exposures to air pollutants, such as nitrogen dioxide and ozone, are significantly associated with asthma-related visits to the emergency department.[25][26] Living near to main roads is linked to increased asthma morbidity.[1]
The mechanisms that lead to such events are not well understood, but may include free radical and oxidative stress, ciliary dyskinesis, epithelial damage, and increased pro-inflammatory mediators.[7][22]
Microbial pollution is one element of indoor air pollution. Respiratory symptoms, allergies, and asthma are associated with dampness and mould in indoor environments.[27] Other major indoor air pollutants that can affect respiratory health include carbon monoxide and carbon dioxide (among others), and sources of indoor air pollution include certain cooking and heating devices.[1] Although air filters can reduce fine particle exposure, they have demonstrated no consistent effect on asthma outcomes.[28]
In a multi-variable model, chronic rhinosinusitis was significantly associated with exacerbation frequency, even after adjustment for multiple factors.[18]
In a multi-variable model, gastro-oesophageal reflux disease was significantly associated with exacerbation frequency, even after adjustment for multiple factors.[18]
Confirmed food allergy is a risk factor for asthma exacerbations, even if the patient has few asthma symptoms.[1]
Eighty percent of patients develop asthma in childhood, and so most adult patients presenting with asthma exacerbations will have a previous diagnosis of asthma.[30]
If a patient requires oral corticosteroids to control their asthma, it implies a more severe, labile form of asthma that also increases risk of sudden, severe, life-threatening asthma exacerbation.
Poor adherence to asthma treatment (especially poor adherence to any prescribed inhaled corticosteroids) is a potentially modifiable risk factor for exacerbations, even in patients with few symptoms.[1]
Suboptimal adherence is seen in up to 75% of patients, and may be unintentional (e.g., cost-related, or due to absence of routine or misunderstanding) or intentional (e.g., due to cultural or religious factors, concerns about safety or adverse effects, or a belief that treatment is not required).[1][13]
Increases the risk of exacerbations even if the patient usually has few asthma symptoms.[1] During pregnancy, asthma exacerbations that require medical intervention occur in about 20% of women with asthma, with about 6% of women being admitted to hospital.[32]
Exacerbations may result from mechanical or hormonal changes and/or be due to asthma drugs being decreased or discontinued on the basis of patient (and/or healthcare provider) concerns around their use during pregnancy.[1] Pregnant women additionally appear to be especially susceptible to the effects of viral respiratory infections, such as influenza.[1] Multiparity, black ethnicity, age >35 years and having severe asthma are all factors that convey an increased risk of exacerbations during pregnancy.[1]
Psychosocial factors, including psychosis, alcohol/drug abuse, financial/employment problems, and learning difficulties, are potentially modifiable risk factors for exacerbations, even in patients with few symptoms.[1][33] There may be poor adherence to asthma drugs (a risk factor for exacerbations) during times of stress or poor mental health.[1]
Studies have shown that people who have had an exacerbation of asthmatic symptoms frequently have a respiratory tract bacterial infection.
Atypical pathogens, such as Mycoplasma pneumoniae and Chlamydia pneumoniae in particular, exacerbate symptoms.[35][36][37] In some studies, evidence of infection with M pneumoniae was found in up to 20% of patients with an acute asthma exacerbation.[35]
Patients with asthma may also develop a chronic M pneumoniae infection, which, in turn, could contribute to the persistence and severity of asthma.[8]
C pneumoniae impairs mucociliary clearance and increases mucus secretion in the airway, and may increase susceptibility to allergic triggers.[38]
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