The first record of asthma-like symptoms was documented in Egyptian manuscripts circa 1500 B.C.E. Hippocrates first referred to asthma as a specific condition, using the Greek word asthma, meaning the act of panting or labored breathing . Asthma-like symptoms and their treatments were described thousands of years ago in ancient Chinese writings. The herbal medicine ma-huang traditionally used in Chinese medicine to treat asthma-like symptoms, comes from the bark of trees of the genus Ephedra equisetina. The modern medication ephedrine, a common ingredient in some asthma medicines, is derived from this plant [6,7].

Since 1958, several attempts have been made to establish a consensus definition of asthma but thus far have been unsuccessful, and ongoing research continues to evolve the definition. The Global Initiative for Asthma (GINA) defines asthma as a "heterogenous disease, usually characterized by chronic airway inflammation" [8]. It is defined by a history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness, and cough, that vary over time and in intensity, together with variable expiratory airflow limitation [8]. This definition comprises elements set forth by other organizations, including the National Asthma Education Prevention Program (NAEPP), that does not recognize asthma as a specific disease with a single cause, but instead is categorized as a "syndrome composed of multiple phenotypes" [9].

Asthma is considered a chronic, albeit reversible, respiratory disorder. This inflammatory condition produces hyper-reactive and hyper-responsive airway and lungs, causing episodic, reversible airway obstruction through bronchospasms, increased mucus secretions, and mucosal edema. The hyper-reactive lungs of a patient with asthma are more sensitive than most individuals' and may become inflamed or edematous when exposed to specific irritants (e.g., cold air, animal dander, dust, tobacco smoke, care exhaust fumes, grass) or by the respiratory involvement of viral infections, exercise, or laughter . The immune system of an individual with asthma will over-react to these irritants, constricting the airways and filling them with mucus; constricted airways interfere with the movement of air in and out of the lungs, making breathing difficult [8,9].

Asthma is marked by recurrent episodes of wheezing, breathlessness, chest tightness, and/or coughing. Usually, these periods are associated with widespread but variable airflow obstruction followed by a period of relief, either spontaneously or in response to treatment. Asthma has many puzzling aspects, and its symptoms may wax and wane, especially seasonally. Unlike other respiratory diseases, such as congestive obstructive pulmonary disease (COPD) and emphysema, in which air trapping and hyperinflation of the lungs also occur, asthma is reversible with the use of proper medications and therapies. Long-term lung tissue damage can occur when asthma attacks occur frequently or when the disorder is poorly controlled. Permanent damage would require many instances of severe attacks. In children, whose lungs are still developing, the risk of long-term damage is greater [8,9].

As noted, approximately 262 million people worldwide are living with asthma. In 2019, there were approximately 461,000 deaths attributed to asthma [3,15]. The incidence and severity of the condition varies globally.

Although for many years asthma was characterized as a condition limited to industrialized countries, it is now recognized as a significant health issue in developing countries as well. More than 40 million people in Central and South America and more than 50 million people in Africa have asthma. More than 80% of asthma deaths occur in developing countries [3,16]. The 2019 Lancet Global Burden of Disease report indicates that countries on the lower and middle parts of the sociodemographic index spectrum sustain the greatest number of asthma deaths, while prevalence of asthma is greatest in countries higher on the sociodemographic index spectrum [15]. Disability-adjusted life-year rates are very high on most of the African continent, as well as in-and-around the Indian subcontinent, southeast Asia, and parts of the United States.

In 2023, 11% of women in America had asthma, compared with 6.8% of men [18]. The higher incidence of asthma among women may produce additional health consequences during pregnancy and/or childbirth. The CDC has found that the asthma rate is 13.3% among individuals with multiple non-Hispanic race/ethnicity, 9.8% among American Indian/Alaska Natives, and 11.7% among non-Hispanic Black individuals. Among Hispanic individuals, the rates are 6.2% for Mexican/Mexican Americans and 7% for people with other Hispanic heritage. Non-Hispanic White individuals have an asthma prevalence of 8.9%, and Asian Americans have an asthma prevalence of 4.9% [18].

Although experts have been unable to definitively identify the cause or causes of asthma, there are several factors that increase the risk of developing the condition in one's lifetime. The following are some of the most common risk factors and will be addressed throughout this course [8,15]:

Environmental allergens (e.g., mold, dander, pollen, dust mites)

Skin or food allergies

Overweight/obesity

Genetic predisposition/family history

Low birth weight

Respiratory infections in childhood

Vitamin D deficiency

Living in an urban area

Exposure to secondhand smoke

Exposure to occupational triggers (e.g., chemicals used in farming, hairdressing)

Gastroesophageal reflux disease (GERD)

There have been many studies illustrating a link between obesity and asthma in adults and children. Research indicates that being overweight or obese significantly increases the risk of developing asthma, worsening asthma symptoms, and poor asthma control [15,19]. The obesity rate among adults with asthma was significantly higher than the rate among adults without asthma (38.8% vs. 26.8%) [19]. One meta-analysis involving more than 300,000 adults in the United States with asthma found that the prevalence is 7.1% in lean adults, compared with 11.1% in obese adults. In addition, the prevalence of asthma in women with obesity was found to be nearly double that of lean women (14.6% vs. 7.9%). Interestingly, men did not have a statistically significant difference in comorbid overweight/obesity asthma [20]. Patients who are excessively overweight place an additional burden on their bodies, especially on their heart and lungs, decreasing both functional residual capacity (the amount of air left in the lungs after exhalation) and tidal volume. These decreases were associated with several factors, including changes in lung development and chronic systemic inflammation, that may affect, induce, or exacerbate asthma symptoms. However, weight is a modifiable risk factor, and researchers have found that total weight loss of 5% or greater significantly improves lung function and asthma control [20].

A genetic predisposition to develop immunoglobulin E (IgE) antibodies has been shown to increase the incidence of allergy and asthma. However, since the mapping of the human genome has been completed, more than 100 susceptibility genes contributing to the development of asthma have been recognized. The first gene associated with asthma susceptibility and airway hyper-responsiveness, ADAM33, was mapped in 2002. Researchers at Channing Laboratory, Brigham and Women's Hospital in Boston, were able to link variants of this gene to a familial history of asthma and asthma symptoms. In 2003, two more genes relating to asthma, PHF11 and DPP10, were identified [13,24]. Results have been mixed regarding the role of Clara cell secretory protein gene variants and the asthma phenotype on the development of asthma, but research seems to indicate a positive, but inconsistent link [25,26].

Although causative chromosomal regions and candidate genes are now being revealed, this has not ruled out the influence of environmental factors in asthma development. In 2013, the results of two studies were analyzed to determine the role of genetic and environmental factors, and the researchers found that variants at the 17q21 locus were implicated in the development of asthma in children with a history of rhinovirus infection with wheezing [27]. This indicates a possible synergistic relationship between genetic and environmental factors in the development of asthma in childhood.

Should a family have a history of allergies and asthma, the first two years of a child's life are critical; exposure to potential allergens during this time increases the likelihood that a child will develop asthma. In addition, early contacts to such potential allergens may contribute to the severity of the child's asthma. Genetic tendency toward lung sensitivity may not follow a direct line; asthma may bypass a generation or surface in other family branches. The exact mode of inheritance is unclear [8,15].

The most obviously affected structures of the respiratory system are the bronchial tubes. As the bronchi stretch deeper into the lungs, they subdivide into smaller bronchioles. A pale, thin membrane, known as the bronchial mucosa, lines these bronchial tubes. Mucous glands, which keep airways lubricated with watery mucus, are embedded within the many layers of bronchial lining. Harmful substances stick to the mucus or sputum and are propelled out of the lungs by the movement of the cilia; this mucus production is one way the body fights infection [8,13].

Asthma is considered a disorder of exhalation, not inhalation. Patients with asthma are uncomfortable not because they cannot inhale enough air, but because obstructed airways are preventing them from exhaling the air that is already in their lungs. In fact, autopsies of patients who died of asthma complications have revealed lungs full of air. When bronchioles narrow during an asthma attack, upstream obstruction causes premature closure of airways with expiration, as pleural pressure becomes greater than the pressure inside the airway (the equal pressure point, or EPP). Downstream airways become compressed with expiration, trapping air in the alveolar sacs. Reduced respiratory muscle efficiency and function can be caused by lung hyperinflation and thoracic hyperexpansion, resulting in air trapping. Respiratory muscle advantage is compromised, and the flattened diaphragm is forced to contract with shortened muscle fibers, resulting in a feeling of chest tightness. This can lead to airway rupture, manifested as pneumothorax, pneumomediastinum, or subcutaneous emphysema [13].

Lymphocytes, a type of white blood cell, are divided into two categories: B cells, which manufacture antibodies or immunoglobulins that identify foreign contacts as harmful agents, and T cells (from the thymus gland), which release chemicals known as cytokines that kill the invading antigen. Antibodies aid the immune system in recognizing organisms that have infected the body in the past, allowing the immune system to fortify and strengthen the body against future invasions by the recognized antigen [8,13].

The pathogenesis of an asthma attack can be described as an inflammatory cascade composed of triggered, acute inflammation and chronic inflammatory changes. In the body of a person without asthma, the immune responses in the bronchi (e.g., swelling, excretion of mucus, recruitment of inflammatory cells) are present in a lesser degree to protect the body against any infectious agents or foreign objects. However, a person with asthma produces an extreme reaction to otherwise relatively harmless irritants, referred to as asthmagens or triggers. Exposure to a trigger causes inflammatory mast cells to release specific inflammatory mediators, including histamine and interleukins, resulting in an acute response. Histamine causes local tissue edema; interleukins generally act as chemotactic factors and activate other inflammatory cells. Studies reveal that leukotrienes, another chemical released by mast cells, prolong bronchial muscle and airway constriction [8,12].

The pathogenesis of an asthma attack can be described as an inflammatory cascade composed of triggered, acute inflammation and chronic inflammatory changes. In the body of a person without asthma, the immune responses in the bronchi (e.g., swelling, excretion of mucus, recruitment of inflammatory cells) are present in a lesser degree to protect the body against any infectious agents or foreign objects. However, a person with asthma produces an extreme reaction to otherwise relatively harmless irritants, referred to as asthmagens or triggers. Exposure to a trigger causes inflammatory mast cells to release specific inflammatory mediators, including histamine and interleukins, resulting in an acute response. Histamine causes local tissue edema; interleukins generally act as chemotactic factors and activate other inflammatory cells. Studies reveal that leukotrienes, another chemical released by mast cells, prolong bronchial muscle and airway constriction [8,12].

After the inflammatory cells are activated, bronchospasm occurs. Bronchospasm and local tissue edema cause narrowing of the airways. Release of interleukins and other chemotactic substances causes migration of other inflammatory cells, including eosinophils, airway macrophages, and neutrophils. The physical presence of these cells can also cause airway narrowing. The migration of the inflammatory cells starts within 30 minutes of exposure and may take hours to reach peak levels.

There are essentially five key elements of an asthma attack: muscle spasm, excess mucus, coughing, wheezing, and fatigue. While not all five elements are present for all patients, they are the most common physical manifestations of an episodic attack of the condition and should be evaluated and treated urgently.

The physical examination should include an assessment of the upper respiratory tract, chest, and skin. One presenting sign is hyperexpansion of the thorax. Patients with severe asthma often develop a barrel-shaped chest due to the forced inhalation and exhalation, which may cause chest and rib muscles to overdevelop. In time, the chest walls stretch out of shape, assuming a rounded appearance. As the patient inhales and exhales deeply, the quality of the breath sounds can be assessed. Sounds of wheezing during normal breathing or a prolonged phase of forced exhalation may indicate asthma. Observing increased nasal secretions, mucosal swelling, sinusitis, rhinitis, nasal polyps, or edema under the eyes are possible signs of allergic asthma. Any of these indications should be noted. Lastly, the skin should be examined for evidence of atopic dermatitis, eczema, or other allergic skin reactions. Red, scaly skin with pruritus may indicate eczema and can signal other forms of allergy and possibly allergy-related asthma.

Most physicians order tests to confirm an asthma diagnosis or to rule out any complications and evaluate the severity of the condition. The objectivity of pulmonary tests allows for a reliable analysis of lung function that patient history and physical examination may not provide; this information may be valuable to the diagnosis process. The most critical tests for evaluating asthma assess pulmonary function, which measures lung performance. Pulmonary tests calculate the amount and rate of air expelled during a single breath, helping to discern whether constricted airways are responsible for blocked airflow [10,21]. Guidelines for normal breathing are based on analysis of data obtained from large segments of the population. A patient's information is plotted on a continuum, allowing comparison to average breathing patterns for healthy individuals of the same sex, age, and size. Two common methods of measuring airflow assess forced expiratory volume (FEV₁) and peak expiratory flow (PEF) [9,10,21].

A spirometer is a simple machine used to determine both the total amount of air that can be forcefully exhaled after maximum inspiration, referred to as forced vital capacity (FVC), and how fully air can be expelled from the lungs, measured by the amount of air forced from the lungs in one second, which is expressed as FEV₁[9,21]. The spirometer is generally used in diagnosis to establish airflow obstruction and reversibility. Obstruction may be ascertained if the FEV₁ is less than 80% of the predicted value or if FEV₁ divided by FVC is less than 65%. Normally, the FEV₁ should account for more than 75% of the FVC; anything less than 75% indicates a possible obstruction and 65% or less may indicate a diagnosis of asthma [9,10,21].

A peak flow meter measures the speed of exhalation. The highest speed or best flow is PEF or peak flow. The peak flow meter is less sophisticated than a spirometer, which provides a more thorough assessment of lung function. However, the meter has the advantages of being less expensive, portable, and easy to use. The severity of a patient's asthma can be determined by careful and consistent monitoring of peak flow and comparison to a patient's best peak flow and to standard measurements. Studies confirm that short-term peak flow measurements assist healthcare providers in assessing asthma severity [8,9,21].

Studies have shown that measuring exhaled nitric oxide (FeNO) is helpful in evaluating and diagnosing asthma, particularly in cases of an uncertain diagnosis of asthma using history, clinical course, clinical findings, and spirometry (including bronchodilator responsiveness testing) or when spirometry cannot be performed [9,10,13]. Nitric oxide is a mediator for the inflammation that occurs during an asthma episode; the amount of nitric oxide measured during exhalation will directly correlate with the inflammation in the bronchial tubes. In general, higher concentrations of nitric oxide are a sign of more severe forms of asthma. However, the NAEPP notes that increased FeNO levels can be caused by allergic rhinitis and atopy, which can be present in individuals with and without asthma; taking these factors into consideration is important for accurate interpretation of FeNO test results [9,10].

In addition to elimination diets and skin testing, there are various blood tests that may be used to assess allergy or allergic reactions in a patient. These tests are able to calculate the proportion of the antibody IgE in the body. In infancy, IgE levels tend to be low, rising gradually over the following decades and decreasing beginning around 40 years of age. Lowest levels are recorded when an individual is 70 years of age. Therefore, high IgE levels can imply that allergies may be triggering the asthma. Elevated IgE levels in infants and young children are one test used to help predict future allergies. Although the analysis is fairly common, it is rarely used as a sole indicator of allergy or allergic asthma. A group of tests, the radioallergosorbent test (RAST), the multiple allergosorbent test (MAST), and the fluorescent allergosorbent test (FAST), evaluate blood levels of IgE for sensitivity to specific allergens [9,10,14].

In particular, panic disorders, physical airway obstructions, congestive heart failure (CHF), GERD, and other pulmonary conditions, such as COPD, pneumonia, and bronchitis, may either exacerbate or mimic the signs and symptoms of asthma. Shortness of breath, decreased exercise tolerance, chest tightness, and wheezing may occur with any of these conditions.

There are also certain medications that may induce asthma-like symptoms. Specifically, there are two conditions, aspirin-sensitive triad and nonallergic rhinitis with eosinophilia syndrome (NARES), known for their similar presentation to asthma. The diagnosis of aspirin-sensitive triad is based on three distinct symptoms: perennial rhinitis, nasal polyps, and asthma. Patients with an aspirin-sensitive triad diagnosis tend to collect all three symptoms gradually, in no particular order, over a period of years or decades. Although it is not known how common nonsteroidal anti-inflammatory drug (NSAID) sensitivity is for adult patients with asthma, various reports site frequencies from 3% to approximately 40%. It is far less common in pediatric patients with asthma; women in their third decade are most commonly affected [9,33].

Quite often, aspirin-sensitie patients with asthma have other related respiratory conditions, including sinusitis, severe rhinitis, and nasal polyps. Nasal polyps are benign inflammatory growths that begin in the sinuses but protrude into the nostril. However, the absence of sinusitis and nasal polyps does not automatically rule out the presence of aspirin sensitivity. Aspirin sensitivity can develop suddenly and produce a reaction similar to anaphylaxis, but it usually builds over many years. Patients with asthma found to have a sensitivity, usually by an aspirin challenge test, are advised to avoid all NSAIDs even if they have not reacted to these medications in the past. Also, patients with aspirin-sensitive triad will often have cross intolerances with sulfides, particularly wine and other alcoholic beverages containing sulfides, and naturally occurring salicylates, which are found in citrus fruit, nuts, and grapes. Food additives may also be problematic [9,33].

In addition to inhalers, many asthma medications are manufactured as pills, granules, or liquids to be ingested orally. Oral medications benefit patients by reaching the small bronchial tubes that most inhaled medication cannot reach. Newer developments in longer-acting, timed-release oral medications adapt to the needs and lifestyles of many patients. However, the amount of medication absorbed over a given time period can vary. Some medications may take up to six times longer than others to reach peak concentrations, which means each patient may require a different dose and frequency of administration to reverse breathing problems [11,13].

The disadvantage associated with oral medications is the systemic distribution. If negative or unpleasant side effects occur, they last the entire time the medication is active in the body. Depending upon the form and dose, oral medication may be more difficult for the system to balance throughout a 12- or 24-hour period than inhaled formulations [11,13].

The first oral medication to become available for the relief of an acute asthma episode was epinephrine, a hormone produced by the sympathetic nervous system. Epinephrine was once the first choice for treating acute asthma, but it has proved to be a weak bronchodilator with quickly diminished action. Moreover, epinephrine has very potent systemic effects, causing tachycardia, high blood pressure, nervousness, headache, and in some cases, panic attacks. However, this medication may still be used intravenously or subcutaneously in severe asthma emergencies. Epinephrine can be described as nonselective; that is, the medication acts on both the lungs and the heart [9,13].

Some learning and behavioral disorders have been found to coexist with asthma. One of these disorders is attention deficit hyperactivity disorder (ADHD), a chronic neurobiochemical condition that normally presents at an early age and includes primary behavior characteristics such as impulsivity, distractibility, short attention span, difficulty concentrating, extreme tempered mental characteristics, and in some cases, hyperactivity. Studies suggest an association between asthma and ADHD, but this association is likely the result of complex and possibly multiple pathways [44]. Results of a systematic review of literature and meta-analysis published in 2018 continued to show a positive association between ADHD and asthma after controlling for possible confounders. More research is needed to determine the cause of the association [45].

As stressed throughout this course, patient education and communication are imperative to the treatment and management of asthma symptoms. It is important that healthcare providers are able to discuss the different aspects of asthma symptoms as well as treatment and management to ensure that patients are able to understand and follow the established plan. In addition to the treatment plan and common symptoms associated with asthma episodes, patient education should outline the importance of compliance, trigger avoidance, and the continuous monitoring of their condition.

For certain patients with asthma, it may be useful to realize that pollen settles quickly in rural areas, reaching ground level between 8:00 p.m. and 10:00 p.m. In the city, hot pavements and buildings keep upward air currents going and pollen stays aloft longer. As most pollen lands in the city between roughly midnight and 2:00 a.m., it may contribute to night-time symptom aggravation in urban patients with asthma. If a patient with asthma has a noticeable response to a specific type of pollen, staying indoors or avoiding heavily wooded areas at release times may help alleviate symptoms. A daily pollution index figure should be available from a regional office of your state's Department of Environmental Conservation [8,47,48]. Many local and online weather stations include pollen counts in their daily reports as well.

The verdict regarding the effects of outdoor pollution on the condition of asthma remains controversial. Consider two main types of outdoor pollution: industrial smog (such as sulfur dioxide) and photochemical smog (a combination of ozone and nitrogen oxides). Physicians and scientists are cautious about implicating these and other environmental pollutants as asthma triggers. But the findings of several studies confirm a relationship between pollutants and asthma, particularly when nitrogen oxide, acid aerosols, and ozone are involved [8,47,48].

Patients with asthma seem to have more frequent symptoms if exposed to high formaldehyde levels. Formaldehyde is common in both gas and liquid forms; the vapors expelled by the compound may irritate the lining of the eyes, nose, and lungs when inhaled. A formaldehyde solution is often used as a preservative in laundry detergents, air fresheners, shampoos, dish soaps, medications, cosmetics, cigarettes, and some processed foods. Additionally, it may be found in manufacturing plastics, wrinkle-free clothes, and some building materials, such as particle board, plywood, pressed board fiberboard, carpet backing, glues, and foam insulation. The frequent use of formaldehyde in the production of so many different items makes it a very commonly encountered irritant. Materials that produce formaldehyde should be eliminated from the environment of patients with asthma as much as possible. If a manufactured product contains formaldehyde, it should be noted that the emissions generally decrease as the item ages. Formaldehyde is also created by the combustion of wood and natural gas. Flues for wood burning fireplaces and stoves must be clear; if smoke can be smelled, there is formaldehyde present in the air. When a natural gas appliance is used, adequate ventilation, preferably with a powered vent, is necessary [8,48,51].

Asthma episodes that are the result of viruses may be severe and sudden in onset; lower respiratory tract symptoms of coughing, wheezing, and shortness of breath can occur within 24 hours after the onset of upper respiratory tract viral symptoms, such as nasal congestion. Occasionally, wheezing may occur without any premonitory upper respiratory tract warning, so the patient with asthma should be alert to the earliest onset of chest symptoms as well as the premonitory upper respiratory tract symptoms that usually precede them. It is known that early treatment, especially with oral corticosteroids, may prevent the often serious asthmatic consequences of a viral infection. It is imperative, therefore, that patients are able to recognize early warning signals. Vaccination for typical respiratory viruses, such as influenza, measles, varicella (chicken pox), and pertussis, should be considered as a preventive measure, especially in children. The CDC Advisory Committee on Immunization Practices and GINA recommend that people with asthma receive either the Moderna or Pfizer-BioNTech COVID-19 vaccine series [8,57].