Asthma

• 1. Defining The Asthma Syndrome

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  In 2019, approximately 262 million people worldwide were affected by asthma. This common long-term inflammatory disease of the airways is characterized by variable and recurring symptoms. Episodes of wheezing, coughing, chest tightness, and shortness of breath define the clinical picture for most patients. A sudden worsening known as an asthma attack occurs when allergens or dust particles are inhaled into the lungs. These events can happen a few times a day or only once per week depending on the individual. Symptoms often become worse at night or during physical exercise. The condition affects medium-sized airways but may progress to involve small or large ones over time. Airway inflammation remains consistent across everyone with asthma regardless of current symptom levels. Cells involved include eosinophils, neutrophils, CD4 T lymphocytes, mast cells, basophils, macrophages, respiratory epithelium, endothelial cells, and smooth muscle cells. Inflammation leads to structural changes such as thickening of the airway smooth muscle and tissue beneath the lining. Increased tissue and matrix buildup occur within the airway wall along with more small blood vessels and nerve fibers. Glands that produce mucus also increase in size. Contraction of airway smooth muscle combined with swelling and excessive mucus production contributes to narrowing of the airways. Airway hyperresponsiveness describes this excessive narrowing in response to stimuli that are normally harmless. This narrowing leads to variable airflow restriction and the characteristic symptoms of the disease.

• 2. Genetic And Environmental Triggers

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  Asthma is caused by a mixture of genetic and external factors manifesting when those with susceptibility face specific environmental exposures. Twin studies support a substantial heritable component with estimates suggesting roughly half or more of asthma susceptibility comes from genetics. Large genome-wide association studies indicate risk reflects cumulative effects of numerous common genetic variants together with limited contributions from rare variants. The chromosome region 17q12, 21 remains the most robustly replicated asthma locus with effects strongest for childhood-onset disease. Multiple genes in this region including ORMDL3 and GSDMB appear to act primarily through regulatory mechanisms. Pathway analyses consistently highlight type 2 inflammation, epithelial barrier function, and both innate and adaptive immune signalling. Factors during pregnancy linked to development include weight gain or obesity in the mother and smoking while pregnant. Early childhood exposure to secondhand smoke increases the likelihood of a child developing asthma. Children whose maternal grandmother smoked during pregnancy are also more likely to develop asthma regardless if their mothers developed asthma or smoked. Chronic exposure to air pollution increases the risk of developing asthma. Outdoor air pollution includes nitrogen dioxide and traffic pollution while indoor air pollution includes biomass pesticides building materials such as asbestos and formaldehyde mold dust mites cockroaches and endotoxins. Asthma is more commonly seen in urban environments than in rural environments due to higher presence of certain risk factors like traffic pollution and social inequality.

• 3. Diagnostic Methods And Spirometry

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  There is currently no precise test for the diagnosis which is typically based on the pattern of symptoms and response to therapy over time. Spirometry measures lung function in terms of amount and speed of air exhaled and inhaled and is recommended to aid in diagnosis and management. It is the single best test for asthma. If the FEV1 measured by this technique improves more than 12% and increases by at least 200 millilitres following administration of a bronchodilator such as salbutamol this supports the diagnosis. In children under the age of six the diagnosis is more difficult as they are too young for spirometry. The methacholine challenge involves inhalation of increasing concentrations of a substance that causes airway narrowing in those predisposed. A positive result means the person has asthma but it is not specific for the disease. Other supportive evidence includes a greater than or equal to 20% difference in peak expiratory flow rate on at least three days in a week for at least two weeks. Testing peak expiratory flow is more variable than spirometry however and thus not recommended for routine diagnosis. Many other conditions can cause symptoms similar to those of asthma including allergic rhinitis sinusitis foreign body aspiration tracheal stenosis laryngotracheomalacia vascular rings enlarged lymph nodes neck masses bronchiolitis and viral infections. Vocal cord dysfunction may present similarly in both populations.

• 4. Evolution Of Treatment Strategies

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  In 1873 one of the first papers in modern medicine tried to explain pathophysiology while another in 1872 concluded asthma could be cured by rubbing chest with chloroform liniment. Medical treatment in 1880 included use of intravenous doses of drug called pilocarpine. In 1905 epinephrine was first referred to as treatment of asthma. The asthma was relieved with this treatment by what was described as vasomotor ataxia of relaxing variety. During 1930s U.S. physician Alvin Barach created quantification of expiratory flow rates to nebulized epinephrine which was first published medical report on effectiveness of bronchodilation. In 1940s first pure beta-agonist synthesized was isoprenaline. Efficacy of anecdotal applications of oral corticosteroids for asthma was published in 1952. Use of pressurized metered dose inhaler developed mid-1950s for administration of adrenaline as well as isoproterenol. Inhaled corticosteroids and selective short-acting beta agonists came into wide use in 1960s. In 1967 adrenergic receptors classified into two subtypes of beta-1 and beta-2 adrenergic receptors. Beta-2 adrenergic receptors found dominant in lungs as well as present in alveolar airspace allowing development of selective beta-2 agonists starting in 1960s. Current guidelines prefer inhaled corticosteroids over short-acting beta agonists due to research suggesting management with SABA alone insufficient to prevent exacerbations.

• 5. Global Epidemiology And Mortality

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  In the United States burden of asthma falls disproportionately on racial and ethnic minorities and economically underprivileged populations. Prevalence highest in non-Hispanic black and Puerto Rican children. Mortality rate for black Americans with asthma two times higher than for white Americans. Neighborhoods predominantly racial and ethnic minority populations affected greater extent than predominantly white neighborhoods by air pollutants significant factor occurrence asthma. Residents areas likely redlined have asthma emergency department visit rates 2.4 times higher residents areas less likely redlined. From 2000 to 2010 average cost per asthma-related hospital stay United States children remained relatively stable at about $3,600 whereas average cost adults increased from $5,200 to $6,600. Medicaid most frequent primary payer among children and adults aged 18, 44 years private insurance second most frequent payer. Among both children and adults lowest-income communities United States higher rate hospital stays asthma 2010 than highest-income communities. Globally causes moderate or severe disability in 19.4 million people 16 million low and middle-income countries. Low- and middle-income countries make up more than 80% mortality.