Asthma

Reactive airways dysfunction syndrome (RADS) and irritant-induced asthma

Reactive airways dysfunction syndrome (RADS) is the rapid onset (minutes to hours, but not > 24 hours) of an asthma-like syndrome that

• Develops in people with no history of asthma

• Occurs following a single, specific inhalation exposure to a significant amount of an irritating gas or particulate

• Persists for ≥ 3 months

Numerous substances have been implicated, including chlorine gas, nitrogen oxide, and volatile organic compounds (eg, from paints, solvents, adhesives). The exposure event is usually obvious to the patient, particularly when symptoms begin almost immediately.

Irritant-induced asthma refers to a similar, persistent asthma-like response following multiple or chronic inhalational exposure to high levels of similar irritants. Manifestations are sometimes more insidious, and thus the connection to the inhalational exposure is clear only in retrospect. See work-related asthma for more information.

RADS and chronic irritant-induced asthma have many clinical similarities to asthma (eg, wheezing, dyspnea, cough, presence of airflow limitation, bronchial hyperresponsiveness) and respond significantly to bronchodilators and often glucocorticoids. Unlike in asthma, the reaction to the inhaled substance is not thought to be an IgE-mediated immune response; low-level exposures do not cause either RADS or irritant-induced asthma. However, repeated exposure to the initiating agent may trigger additional symptoms.

Etiology references

1. 1. Murrison LB, Ren X, Preusse K, et al: TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk. J Allergy Clin Immunol 149(1):79–88, 2022. doi:10.1016/j.jaci.2021.05.033

2. 2. Hoang TT, Sikdar S, Xu CJ, et al: Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study. Eur Respir J 56(3):2000217, 2020. Published 2020 Sep 3. doi:10.1183/13993003.00217-2020

3. 3. Kozik AJ, Holguin F, Segal LN, et al: Microbiome, Metabolism, and Immunoregulation of Asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report. Am J Respir Cell Mol Biol 67(2):155–163, 2022. doi:10.1165/rcmb.2022-0216ST

4. 4. Peters U, Dixon AE, Forno E: Obesity and asthma. J Allergy Clin Immunol 141(4):1169–1179, 2018. doi: 10.1016/j.jaci.2018.02.004

5. 5. Wang Y, Guo D, Chen X, Wang S, Hu J, Liu X: Trends in asthma among adults in the United States, National Health and Nutrition Examination Survey 2005 to 2018. Ann Allergy Asthma Immunol 129(1):71–78.e2, 2022. doi:10.1016/j.anai.2022.02.019

Asthma triggers

Common triggers of an asthma exacerbation include the following:

• Environmental and occupational allergens (numerous)

• Cold, dry air

• Infections

• Exercise

• Inhaled irritants

• Emotion

• Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)

• Gastroesophageal reflux disease (GERD)

Atopy (the genetic predisposition to form allergen-induced IgE responses) is the most significant identifiable risk factor for developing asthma (4). Allergic rhinitis often coexists with asthma; allergic triggers responsible for the inflammatory response in the upper airway (ie, rhinitis) may also be involved in causing similar responses in the lower airway (ie, asthma). Multiple studies have shown that rhinitis itself, even without allergen inhalation, can be an independent risk factor for asthma through shared mechanisms of airway inflammation and nasal-bronchial reflexes (5, 6).

Infectious triggers in young children include respiratory syncytial virus, rhinovirus, and parainfluenza virus infection. In older children and adults, upper respiratory infections (particularly with rhinovirus) and pneumonia are common infectious triggers. Exercise can be a trigger, especially in cold or dry environments, and cold air alone can also trigger bronchoconstriction. Inhaled irritants, such as air pollution, cigarette smoke, perfumes, and cleaning products can also trigger symptoms in patients with asthma. Inhaled irritants that trigger asthma exacerbations do so by inducing a T2 response, in contrast to what happens in reactive airways dysfunction syndrome and chronic irritant-induced asthma. Emotions such as anxiety, anger, and excitement sometimes trigger exacerbations.

Aspirin and other NSAIDs are triggers for exacerbations in up to 30% of patients with nasal polyps and in approximately 9% of all patients with asthma (7). Aspirin -exacerbated respiratory disease is typically accompanied by chronic rhinosinusitis with nasal polyposis. This condition is also known as Samter's triad (asthma, nasal polyposis, and sensitivity to aspirin and other cyclooxygenase-1 [COX-1]-inhibiting NSAIDs).

GERD is a common trigger among some patients with asthma, possibly via esophageal acid-induced reflex bronchoconstriction or by microaspiration of acid. However, treatment of asymptomatic GERD (eg, with proton pump inhibitors) does not seem to improve asthma control.

Response

In the presence of triggers, there is reversible airway narrowing and uneven lung ventilation. In lung regions distal to narrowed airways, relative perfusion exceeds relative ventilation; thus, alveolar oxygen tensions decrease and alveolar carbon dioxide tensions increase. Usually, regional hypoxia and hypercarbia trigger compensatory pulmonary vasoconstriction to match regional ventilation and perfusion; however, these compensatory mechanisms can fail during an asthma exacerbation due to the vasodilatory effects of prostaglandins that are upregulated during an exacerbation. Most patients can compensate by hyperventilating, but during severe exacerbations, diffuse bronchoconstriction may lead to severe air trapping. Bronchoconstriction coupled with air trapping places the respiratory muscles at a marked mechanical disadvantage so that the work of breathing increases. Under these conditions, hypoxemia worsens and PaCO2 rises. Respiratory acidosis and metabolic acidosis may result and, if left untreated, cause respiratory and cardiac arrest.

Pathophysiology references

1. 1. Hudey SN, Ledford DK, Cardet JC: Mechanisms of non-type 2 asthma. Curr Opin Immunol 66:123–128, 2020. doi:10.1016/j.coi.2020.10.002

2. 2. Tliba O, Panettieri RA Jr: Paucigranulocytic asthma: Uncoupling of airway obstruction from inflammation. J Allergy Clin Immunol 143(4):1287–1294, 2019. doi:10.1016/j.jaci.2018.06.008

3. 3. Busse WW, Lemanske RF Jr: Asthma. N Engl J Med 344(5):350–362, 2001. doi:10.1056/NEJM200102013440507

4. 4. National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7223/

5. 5. Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F: Perennial rhinitis: An independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 104(2 Pt 1):301–304, 1999. doi:10.1016/s0091-6749(99)70370-2

6. 6. Shaaban R, Zureik M, Soussan D, et al: Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 372(9643):1049–1057, 2008. doi:10.1016/S0140-6736(08)61446-4

7. 7. American Academy of Allergy, Asthma, and Immunology: Aspirin-Exacerbated Respiratory Disease (AERD). October 31, 2023. Accessed May 20, 2025.

Severity

Severity is the intrinsic intensity of the disease process (ie, how bad it is—see table Classification of Asthma Severity). Severity can usually be assessed directly only before treatment is started, because patients who have responded well to treatment by definition have few symptoms. Asthma severity is categorized as:

• Intermittent

• Mild persistent

• Moderate persistent

• Severe persistent

It is important to remember that the severity category does not predict how serious an exacerbation a patient may have. For example, a patient who has mild asthma with long periods of no or mild symptoms and normal pulmonary function may have a severe, life-threatening exacerbation.

Control

Control is the degree to which symptoms, impairments, and risks are minimized by treatment. Control is the parameter assessed in patients receiving treatment. The goal is for all patients to have well-controlled asthma regardless of disease severity. Control is classified as:

• Well controlled

• Not well controlled

• Very poorly controlled

Severity and control are assessed in terms of patient impairment and risk (see tables Classification of Asthma Severity and Classification of Asthma Control).

Asthma Attack

3D Model

Impairment

Impairment refers to the frequency and intensity of patients' symptoms and functional limitations (see table Classification of Asthma Severity). Impairment is assessed using similar criteria to severity, but differs from severity by its emphasis on symptoms and functional limitations rather than the intrinsic intensity of the disease process. Lung function or physiologic, objective impairment can be measured by spirometry, mainly forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC), which correlate strongly with subjective components of asthma control that includes symptoms and clinical features such as the following:

• How often symptoms are experienced

• How often the patient awakens at night

• How often the patient uses a reliever (rescue inhaler) for symptom relief

• How often asthma interferes with normal activity

Risk

Risk refers to the likelihood of future exacerbations or decline in lung function and the risk of adverse medication effects. Risk is assessed by long-term trends in spirometry and clinical features such as:

• Frequency of need for oral glucocorticoids

• Need for hospitalization

• Need for intensive care unit (ICU) admission

• Need for intubation

Pulmonary function tests

Patients suspected of having asthma should undergo pulmonary function testing to confirm and quantify the severity and reversibility of airway obstruction. Pulmonary function data quality is effort-dependent and requires patient instruction before the test. If it is safe to do so, bronchodilators should be discontinued before the test: 4 hours for short-acting beta-2 agonists (eg, albuterol); 24 hours for long-acting beta-2 agonists (eg, salmeterol, formoterol); 36 to 48 hours for ultra-long acting beta-2 agonists (eg, indacaterol, vilanterol); 12 hours for muscarinic antagonists that are short-acting (eg, ipratropium); and 48 hours for long-acting ones (eg, tiotropium).to confirm and quantify the severity and reversibility of airway obstruction. Pulmonary function data quality is effort-dependent and requires patient instruction before the test. If it is safe to do so, bronchodilators should be discontinued before the test: 4 hours for short-acting beta-2 agonists (eg, albuterol); 24 hours for long-acting beta-2 agonists (eg, salmeterol, formoterol); 36 to 48 hours for ultra-long acting beta-2 agonists (eg, indacaterol, vilanterol); 12 hours for muscarinic antagonists that are short-acting (eg, ipratropium); and 48 hours for long-acting ones (eg, tiotropium).

Spirometry should be performed before and after inhalation of a short-acting bronchodilator. Signs of airflow limitation before bronchodilator inhalation include reduced FEV1 and a reduced FEV1/FVC ratio. The FVC may also be decreased because of air trapping, such that lung volume measurements may show an increase in the residual volume, the functional residual capacity, or both. A bronchodilator response should be determined by the following equation:

where predicted value is either FEV1 or FVC. A change of > 10% is considered a positive bronchodilator response (3). (Absence of a positive bronchodilator response should not preclude a therapeutic trial of long-acting bronchodilators.

Flow-volume loops should also be reviewed to diagnose vocal fold dysfunction, a common cause of upper airway obstruction that mimics asthma. However, vocal fold dysfunction is intermittent, and normal flow-volume loops do not exclude this condition.

Provocative testing, in which inhaled methacholine (or alternatives, such as inhaled histamine, in which inhaled methacholine (or alternatives, such as inhaled histamine,adenosine, or bradykinin, or exercise testing) is used to provoke bronchoconstriction, is indicated for patients suspected of having asthma who have normal findings on spirometry and flow-volume testing and for patients suspected of having cough-variant asthma, provided there are no contraindications. Contraindications include FEV1 < 1 L or < 50% predicted, recent myocardial infarction or stroke, and severe hypertension (systolic BP > 200 mm Hg; diastolic BP > 100 mm Hg). A decline in FEV1 of ≥ 20% (> 12% in children) from baseline on a provocative testing protocol is relatively specific for the diagnosis of asthma (4). However, FEV1 may decline in response to medications used in provocative testing in other disorders, such as COPD. If FEV1 decreases by < 20% by the end of the testing protocol, asthma is less likely to be present.

Other tests

Other tests may be helpful in some circumstances:

• Diffusing capacity for carbon monoxide (DLCO)

• Chest radiography

• Allergy testing

• Fractional exhaled nitric oxide (FeNO)

DLCO testing can help distinguish asthma from COPD. Values are normal or slightly elevated in asthma and usually reduced in COPD, particularly in patients with emphysema.

A chest radiograph may help exclude some causes of asthma or alternative diagnoses, such as heart failure or pneumonia. The chest radiograph in asthma is usually normal but may show hyperinflation or segmental atelectasis, a sign of mucous plugging. Infiltrates, especially those that come and go and that are associated with findings of central bronchiectasis, suggest allergic bronchopulmonary aspergillosis.

Allergy testing in the skin or blood may be indicated for children whose history suggests allergic triggers (particularly for allergic rhinitis) because these children may benefit from immunotherapy. It should be considered for adults whose history indicates relief of symptoms with allergen avoidance and for those in whom a trial of therapeutic anti-IgE antibody therapy is being considered. Skin testing and measurement of allergen-specific IgE via radioallergosorbent testing (RAST) can identify specific allergic triggers.

Blood tests may be indicated. Elevated blood eosinophils (>150 to 300 cells/mcL [> 0.15 × 10⁹ /L to 0.3 × 10⁹/L]) and elevated nonspecific IgE levels are suggestive but are neither sensitive nor specific for a diagnosis of allergic asthma. Furthermore, some studies have indicated that eosinophil levels may vary diurnally and with other factors (5). Generally, blood eosinophil levels are higher in the morning, and there may be falsely low eosinophil counts when samples are collected in the afternoon. The diurnal fluctuations in eosinophil levels highlight the importance of carefully timing sample collection and conducting multiple measurements to ensure accurate asthma diagnosis and management.

In patients ≥ 5 years who are glucocorticoid-naive, FeNO may be used in the evaluation when the diagnosis of asthma is unclear, especially in children, and it can be used as a biomarker to monitor disease severity and therapeutic efficacy (6). FeNO levels > 50 ppb are consistent with allergic airways inflammation, supporting an asthma diagnosis. A level < 25 ppb is more consistent with an alternative diagnosis. Levels between 25 and 50 ppb are indeterminate. Treatment with glucocorticoids reduces eosinophilic airway inflammation; therefore, FeNO thresholds are lower in patients taking glucocorticoids (4). For patients treated with medium-dose inhaled glucocorticoids, a FeNO level ≥ 25 ppb is considered consistent with allergic airway inflammation; for patients treated with high-dose inhaled glucocorticoids, a FeNO level ≥ 20 ppb is considered consistent.

Sputum evaluation for eosinophils is not commonly done; finding large numbers of eosinophils is suggestive of asthma but not sensitive or specific.

Peak expiratory flow (PEF) measurements with handheld flow meters are recommended for home monitoring of disease severity and for guiding therapy.

Clinical Calculators

Peak Expiratory Flow Prediction

Evaluation of exacerbations

Patients with asthma with an acute exacerbation are evaluated based on clinical criteria but should sometimes also have certain tests:

• Pulse oximetry

• Sometimes peak expiratory flow (PEF) measurement

• FeNO

The decision to treat an exacerbation is based primarily on an assessment of signs and symptoms. PEF measures can help establish the severity of an exacerbation but are most commonly used to monitor response to treatment in outpatients. PEF values are interpreted in light of the patient’s personal best, which may vary widely among patients who are equally well controlled. A 15 to 20% reduction from this baseline indicates a significant exacerbation. When baseline values are not known, the percent predicted PEF based on age, height, and sex may be used, but this is less accurate than a comparison to the patient's personal best.

Although spirometry (eg, FEV1) reflects airflow more accurately than PEF, it is impractical in most urgent outpatient and emergency department settings (ie, in patients with a severe exacerbation needing emergent treatment). It may be used for office-based monitoring of treatment or when objective measures are required (eg, when an exacerbation appears to be more severe than perceived by the patient or is not recognized).

Chest radiograph is not necessary for most exacerbations but should be performed in patients with symptoms or signs suggestive of pneumonia, pneumothorax, or pneumomediastinum.

Arterial or venous blood gas measurements should be initiated in patients with marked respiratory distress or symptoms and signs of impending respiratory failure.

FeNO measurement has been proposed as an adjunct in evaluation of asthma control in patients with confusing or unclear histories or clinical scenarios. Higher baseline FeNO levels are linked to improved asthma control and reduced exacerbation rates. FeNO remains detectable during treatment with immunomodulatory medications, however, its dynamics while on such treatments require further investigation (7).

Diagnosis references

1. 1. Asthma: Updated Diagnosis and Management Recommendations from GINA [practice guideline]. Am Fam Physician 101(12):762-763, 2020.

2. 2. Leung JM, Sin DD: Asthma-COPD overlap syndrome: pathogenesis, clinical features, and therapeutic targets. BMJ 358:j3772, 2017. Published 2017 Sep 25. doi:10.1136/bmj.j3772

3. 3. Stanojevic S, Kaminsky DA, Miller MR, et al: ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 60(1):2101499, 2022. Published 2022 Jul 13. doi:10.1183/13993003.01499-2021

4. 4. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2025. Updated May 2025. Accessed May 20, 2025. Available from www.ginasthma.org

5. 5. Gibson PG: Variability of blood eosinophils as a biomarker in asthma and COPD. Respirology 23(1):12–13, 2018. doi: 10.1111/resp.13200

6. 6. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al: 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 146(6):1217–1270, 2020. doi: 10.1016/j.jaci.2020.10.003

7. 7. Pianigiani T, Alderighi L, Meocci M, et al: Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review. : Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review.Antioxidants (Basel). 12(2):400, 2023. doi:10.3390/antiox12020400

Control of triggering factors

Exposure to triggering factors in some patients may be controlled with use of synthetic fiber pillows and impermeable mattress covers and frequent washing of bed sheets, pillowcases, and blankets in hot water. Ideally, upholstered furniture, soft toys, carpets, curtains, and pets should be removed, at least from the bedroom, to reduce dust mites and animal dander. Dehumidifiers should be used in basements and in other poorly aerated, damp rooms to reduce mold. Steam cleaning of carpeting and upholstery reduces dust mite allergens. House cleaning and extermination to eliminate cockroach exposure are especially important. Although control of triggering factors is more difficult in urban environments, their significance remains unchanged.

High-efficiency particulate air (HEPA) vacuums and filters may relieve symptoms, but no beneficial effects on pulmonary function and on the need for medications have been observed.

Sulfite-sensitive patients should avoid sulfite-containing food (eg, certain wines and salad dressings).

Nonallergenic triggers, such as cigarette smoke, strong odors, irritant fumes, cold temperatures, and high humidity should also be avoided or controlled when possible. Limiting exposure to people with viral upper respiratory infections is also important. However, exercise-induced bronchoconstriction is not treated with exercise avoidance because exercise is important for health reasons. Instead, a short-acting bronchodilator is given prophylactically before exercise and as needed during or after exercise (reliever); controller therapy (step 2 and above in Table Steps of Asthma Management) should be started if exercise-induced symptoms are not responsive to reliever therapy or occur daily or more frequently.

Patients with aspirin-exacerbated respiratory disease should avoid cyclooxygenase-1 (COX-1) inhibitors, such as aspirin. When these patients need a pain reliever, they can use acetaminophen, choline magnesium salicylate, or a COX-2-specific inhibitor, such as celecoxib. , choline magnesium salicylate, or a COX-2-specific inhibitor, such as celecoxib.Aspirin desensitization allows patients to tolerate aspirin and, by extension, COX-1 inhibition when maintained on a daily dose of aspirin post-desensitization.

Asthma is a relative contraindication to the use of nonselective beta-blockers (eg, propranolol, timolol, carvedilol, nadolol, sotalol), including topical formulations, but cardioselective medications (eg, metoprolol, atenolol) probably have no adverse effects.Asthma is a relative contraindication to the use of nonselective beta-blockers (eg, propranolol, timolol, carvedilol, nadolol, sotalol), including topical formulations, but cardioselective medications (eg, metoprolol, atenolol) probably have no adverse effects.

Pharmacotherapy

Major medications classes commonly used in the treatment of asthma and asthma exacerbations include:

• Bronchodilators (beta or beta-2 adrenergic receptor agonists, anticholinergics)

• Glucocorticoids

• Leukotriene modifiers

• Mast cell stabilizers

• Methylxanthines

• Biologic medications

Medications in these classes (see table Pharmacologic Treatment of Asthma) are inhaled, taken orally, or injected subcutaneously or intravenously; inhaled medications come in aerosolized and powdered forms. Use of aerosolized forms with a spacer or holding chamber facilitates deposition of the medication in the airways rather than the pharynx; patients are advised to wash and dry their spacers after each use to prevent bacterial contamination. In addition, use of aerosolized forms requires coordination between actuation of the inhaler (drug delivery) and inhalation; powdered forms reduce the need for coordination, because medication is delivered only when the patient inhales. For details, see Pharmacologic Treatment of Asthma.

Bronchial thermoplasty

Bronchial thermoplasty is a bronchoscopic technique in which heat is applied through a device that transfers localized controlled radiofrequency waves to the airways. The heat decreases the amount of airway smooth muscle remodeling (and thus the smooth muscle mass) that occurs with asthma. In both experimental and observational studies in patients with severe persistent asthma not controlled with multiple therapies, there have been modest decreases in exacerbation frequency and improvement in asthma symptom control (1, 2). However, some patients have experienced an immediate worsening of symptoms, sometimes requiring hospitalization immediately after the procedure. Expert recommendations are to avoid bronchial thermoplasty unless a patient places a low value on the potential for adverse outcomes and a high value on short-term potential benefits. If possible, bronchial thermoplasty should be done in centers with experience in the procedure (3).

Criteria for consideration of bronchial thermoplasty include severe asthma not controlled with inhaled glucocorticoids and long-acting beta agonists, intermittent or continuous use of oral glucocorticoids, FEV1 ≥ 50% of predicted, and no history of life-threatening exacerbations. Patients should understand the risk of post-procedure asthma exacerbation and need for hospitalization before proceeding with the procedure. There are limited data in patients with > 3 exacerbations per year or an FEV1 < 50% of predicted because these patients were excluded from the clinical trials (4).

Monitoring response to treatment

Guidelines recommend office use of spirometry (FEV1, FEV1/FVC, FVC) to measure airflow limitation and assess impairment and risk. Spirometry should be repeated at least every 1 to 2 years in patients with asthma to monitor disease progression. A step-up in therapy might be required if lung function declines or becomes impaired with evidence of increased airflow obstruction (see table Classification of Asthma Control). Outside the office, home peak expiratory flow (PEF) monitoring, in conjunction with patient symptom diaries and the use of an asthma action plan, is especially useful for charting disease progression and response to treatment in patients with moderate to severe persistent asthma. When asthma is quiescent, one PEF measurement in the morning suffices. Should PEF measurements fall to < 80% of the patient’s personal best, then twice per day monitoring to assess circadian variation is useful. Circadian variation of > 20% indicates airway instability and the need to re-evaluate the therapeutic regimen (5).

Patient education

The importance of patient education cannot be overemphasized. Patients do better when they know more about asthma—what triggers an exacerbation, what medication to use when, proper inhaler technique, how to use a spacer with a metered-dose inhaler (MDI), and the importance of early use of glucocorticoids in exacerbations. Every patient should have a written action plan for day-to-day management, especially for management of acute exacerbations, that is based on the patient’s best personal peak flow rather than on a predicted normal value. Such a plan leads to much better asthma control, largely attributable to improved adherence to therapies.

Treatment of acute asthma exacerbation

The goal of asthma exacerbation treatment is to relieve symptoms and return patients to their best lung function. Treatment includes:

• Inhaled bronchodilators (beta-2 agonists and anticholinergics)

• Usually systemic glucocorticoids

Details of the treatment of acute asthma exacerbations, including of severe attacks requiring hospitalization, are discussed elsewhere.

Treatment of chronic asthma

Asthma guidelines recommend treatment based on the severity classification (3, 6). Continuing therapy is based on assessment of control (see table Classification of Asthma Control). Therapy is increased in a stepwise fashion (see table Steps of Asthma Management) until the best control of impairment and risk is achieved (step-up). Before therapy is stepped up, adherence, exposure to environmental factors (eg, trigger exposure), and presence of comorbid conditions (eg, obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, obstructive sleep apnea, vocal fold dysfunction, inhaled cocaine use) are reviewed. These factors should be addressed before escalating (stepping up) medication therapy. Once asthma has been well controlled for at least 3 months, pharmacotherapy is reduced if possible to the minimum that maintains good control (step-down). For specific medications, see table Pharmacologic Treatment of Chronic Asthma.

Exercise-induced bronchoconstriction

Exercise-induced bronchoconstriction can generally be prevented by prophylactic inhalation of a short-acting beta-2 agonist or mast cell stabilizer before starting the exercise. If beta-2 agonists are not effective or if exercise-induced bronchoconstriction causes symptoms daily or more frequently, the patient requires controller therapy.

Aspirin-exacerbated respiratory disease

The primary treatment for aspirin-exacerbated respiratory disease is avoidance of aspirin and other NSAIDs. Celecoxib does not appear to be a trigger. Leukotriene modifiers can blunt the response to NSAIDs. Alternatively, desensitization can be done in either the inpatient or outpatient clinic setting depending on the severity of and other NSAIDs. Celecoxib does not appear to be a trigger. Leukotriene modifiers can blunt the response to NSAIDs. Alternatively, desensitization can be done in either the inpatient or outpatient clinic setting depending on the severity ofaspirin sensitivity and asthma severity; desensitization has been successful in the majority of patients who are able to continue desensitization treatment for more than one year.

Investigational therapies

Multiple therapies are being developed to target specific components of the inflammatory cascade. Therapies directed at interleukin 6 (IL-6), tumor necrosis factor-alpha, other chemokines, and cytokines or their receptors are all under investigation or consideration as therapeutic targets.

Treatment references

1. 1. Chupp G, Kline JN, Khatri SB, et al: Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study. Chest 161(3):614–628, 2022. doi:10.1016/j.chest.2021.10.044

2. 2. Torrego A, Herth FJ, Munoz-Fernandez AM, et al: Bronchial Thermoplasty Global Registry (BTGR): 2-year results. BMJ Open 11(12):e053854, 2021. doi:10.1136/bmjopen-2021-053854

3. 3. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al: 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 146(6):1217–1270, 2020. doi: 10.1016/j.jaci.2020.10.003

4. 4. Langton D, Ing A, Fielding D, et al: Safety and Effectiveness of Bronchial Thermoplasty When FEV₁ Is Less Than 50. Chest 157(3):509–515, 2020. doi:10.1016/j.chest.2019.08.2193

5. 5. Künzli N, Stutz EZ, Perruchoud AP, et al: Peak flow variability in the SAPALDIA study and its validity in screening for asthma-related conditions. The SPALDIA Team. Am J Respir Crit Care Med 160(2):427–434, 1999. doi:10.1164/ajrccm.160.2.9807008

6. 6. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2025. Updated May 2025. Accessed May 20, 2025. Available from www.ginasthma.org

Infants, children, and adolescents

Asthma is difficult to diagnose in infants; thus, under-recognition and undertreatment are common (see also Wheezing and Asthma in Infants and Young Children). Empiric trials of inhaled bronchodilators and anti-inflammatory medications may be helpful. Medications may be given by nebulizer or metered-dose inhaler (MDI) with a holding chamber with or without a face mask. Infants and children < 5 years who require treatment > 2 times/week should be given daily anti-inflammatory therapy with inhaled glucocorticoids (preferred), leukotriene receptor antagonists, or cromolyn. The nebulized route of administration is preferred in children under the age of 2 years. 2 times/week should be given daily anti-inflammatory therapy with inhaled glucocorticoids (preferred), leukotriene receptor antagonists, or cromolyn. The nebulized route of administration is preferred in children under the age of 2 years.

Children > 5 years and adolescents with asthma should not receive long-acting muscarinic antagonists. Also, zileuton should only be used in children ≥ 12 years. Children > 5 years of age and adolescents with asthma should be encouraged to maintain physical activities, exercise, and sports participation. Predicted norms for pulmonary function tests in adolescents are closer to childhood (not adult) standards. Adolescents and mature younger children should participate in developing their own asthma management plans and establishing their own goals for therapy to improve adherence. The action plan should be understood by teachers and school nurses to ensure reliable and prompt access to rescue (reliever) medications. Cromolyn and nedocromil are often tried in this group but are not as beneficial as inhaled glucocorticoids. Long-acting medications may prevent the problems (eg, inconvenience, embarrassment) of having to take medications at school. However, older children and adolescents may be educated and instructed to carry albuterol for self-directed use prior to planned exercise to prevent exercise-induced bronchoconstriction.5 years and adolescents with asthma should not receive long-acting muscarinic antagonists. Also, zileuton should only be used in children ≥ 12 years. Children > 5 years of age and adolescents with asthma should be encouraged to maintain physical activities, exercise, and sports participation. Predicted norms for pulmonary function tests in adolescents are closer to childhood (not adult) standards. Adolescents and mature younger children should participate in developing their own asthma management plans and establishing their own goals for therapy to improve adherence. The action plan should be understood by teachers and school nurses to ensure reliable and prompt access to rescue (reliever) medications. Cromolyn and nedocromil are often tried in this group but are not as beneficial as inhaled glucocorticoids. Long-acting medications may prevent the problems (eg, inconvenience, embarrassment) of having to take medications at school. However, older children and adolescents may be educated and instructed to carry albuterol for self-directed use prior to planned exercise to prevent exercise-induced bronchoconstriction.

Pregnant patients

Approximately 60% of pregnant patients with asthma notice worsening (at times to a severe degree), and 40% notice no change (1). Gastroesophageal reflux disease (GERD) may be an important contributor to symptomatic disease in pregnancy. Asthma control during pregnancy is crucial because poorly controlled maternal disease can result in increased prenatal mortality, premature delivery, and low birth weight.

Asthma medications have not been shown to have adverse fetal effects, but safety data are lacking. ( In general, uncontrolled asthma is more of a risk to mother and fetus than adverse effects due to asthma medications. During pregnancy, normal blood PCO2 level is about 32 mm Hg (2). Therefore, carbon dioxide retention is probably occurring if PCO2 approaches 40 mm Hg.

Older patients

Older patients have a high prevalence of other obstructive lung disease (eg, COPD), so it is important to determine the magnitude of the reversible component of airflow obstruction (eg, by administering a 2- to 3-week trial of inhaled glucocorticoids or pulmonary function testing with bronchodilator challenge). Older patients may be more sensitive to adverse effects of beta-2 agonists and inhaled glucocorticoids. Patients requiring inhaled glucocorticoids, particularly those with risk factors for osteoporosis, may benefit from measures to preserve bone density (eg, calcium and vitamin D supplements, bisphosphonates).), so it is important to determine the magnitude of the reversible component of airflow obstruction (eg, by administering a 2- to 3-week trial of inhaled glucocorticoids or pulmonary function testing with bronchodilator challenge). Older patients may be more sensitive to adverse effects of beta-2 agonists and inhaled glucocorticoids. Patients requiring inhaled glucocorticoids, particularly those with risk factors for osteoporosis, may benefit from measures to preserve bone density (eg, calcium and vitamin D supplements, bisphosphonates).

Special populations references

1. 1. Stevens DR, Perkins N, Chen Z, et al: Determining the Clinical Course of Asthma in Pregnancy. J Allergy Clin Immunol Pract 10(3):793-802.e10, 2022. doi:10.1016/j.jaip.2021.09.048

2. 2. Jensen D, Duffin J, Lam YM, et al: Physiological mechanisms of hyperventilation during human pregnancy. Respir Physiol Neurobiol 161(1):76–86, 2008. doi:10.1016/j.resp.2008.01.001

Prognosis references

1. 1. Grad R, Morgan WJ: Long-term outcomes of early-onset wheeze and asthma. J Allergy Clin Immunol 130(2):299–307, 2012. doi:10.1016/j.jaci.2012.05.022

2. 2. Sears MR, Greene JM, Willan AR, et al: A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med 349(15):1414–1422, 2003. doi:10.1056/NEJMoa022363

3. 3. Kearns N, Maijers I, Harper J, Beasley R, Weatherall M: Inhaled Corticosteroids in Acute Asthma: A Systemic Review and Meta-Analysis. J Allergy Clin Immunol Pract 8(2):605-617.e6, 2020. doi:10.1016/j.jaip.2019.08.051