Asthma: Background, Anatomy, Pathophysiology (original) (raw)

Background

Asthma is a common chronic disease worldwide and affects approximately 26.8 million persons in the United States. [1] It is the most common chronic disease in childhood, affecting an estimated 4.5 million children, and it is a common cause of hospitalization for children in the United States.

The pathophysiology of asthma is complex and involves airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. (See the image below.) The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth-muscle hyperplasia, and airway remodeling are present. [2, 3, 4]

Pathogenesis of asthma. Antigen presentation by dendritic cell with lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.

Airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells (eg, mast cells or nonmyelinated sensory neurons). The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

Physical findings vary with the severity of the asthma and with the absence or presence of an acute episode and its severity. The severity of asthma is classified as intermittent, mild persistent, moderate persistent, or severe persistent. Patients with asthma of any level of severity may have mild, moderate, or severe exacerbations.

Guidelines from the National Asthma Education and Prevention Program (NAEPP) have highlighted the importance of correctly diagnosing asthma by establishing the following [5] :

Episodic symptoms of airflow obstruction are present
Airflow obstruction or symptoms are at least partially reversible
Exclusion of alternative diagnoses

Spirometry with postbronchodilator response should be obtained as the primary test to establish the asthma diagnosis. Pulse oximetry is desirable in all patients with acute asthma to exclude hypoxemia. Chest radiography remains the initial imaging evaluation in most individuals with symptoms of asthma, but in most patients with asthma, the findings are normal or may indicate hyperinflation. Exercise spirometry is the standard method for assessing patients with exercise-induced bronchoconstriction.

Pharmacologic management includes the use of relief and control agents. Control agents include inhaled corticosteroids, long-acting bronchodilators (beta agonists and anticholinergics), theophylline, leukotriene modifiers, antibodies to immunoglobulin E (IgE), and antibodies to interleukin (IL)-5, IL-4, and IL-13. Relief medications include short-acting bronchodilators, systemic corticosteroids, and ipratropium. With severe exacerbations, indications for hospitalization are based on findings after the patient receives three doses of an inhaled bronchodilator. In general, patients should be assessed every 1-6 months for asthma control.

Environmental exposures and irritants can play a strong role in symptom exacerbations. The use of skin testing or in-vitro testing to assess sensitivity to perennial indoor allergens is important. Once the offending allergens are identified, patients should receive counseling on how to avoid them. Efforts should focus on the home, where specific triggers include dust mites, animals, cockroaches, mold, and pollen.

Anatomy

The airways of the lungs consist of cartilaginous bronchi, membranous bronchi, and gas-exchanging bronchi termed the respiratory bronchioles and alveolar ducts. Although the first two types function mostly as anatomic dead space, they also contribute to airway resistance. The smallest non-gas-exchanging airways, the terminal bronchioles, are approximately 0.5 mm in diameter; airways are considered small if they are less than 2 mm in diameter. [6]

Airway structure consists of the following:

Mucosa, which is composed of epithelial cells that are capable of specialized mucus production and a transport apparatus
Basement membrane
Smooth-muscle matrix extending to the alveolar entrances
Predominantly fibrocartilaginous or fibroelastic supporting connective tissue

Cellular elements include mast cells, which are involved in the complex control of releasing histamine and other mediators. Basophils, eosinophils, neutrophils, and macrophages also are responsible for extensive mediator release in the early and late stages of bronchial asthma. Stretch and irritant receptors reside in the airways, as do cholinergic motor nerves, which innervate the smooth muscle and glandular units. In bronchial asthma, smooth-muscle contraction in an airway is greater than would be expected for its size if it were functioning normally, and this contraction varies in its distribution.

Pathophysiology

The 2020 update of the NAEPP guidelines noted the following key changes in the understanding of the pathophysiology of asthma [5] :

The critical role of inflammation is further substantiated, but evidence is emerging for considerable variability in the pattern of inflammation, thus indicating phenotypic differences that may influence treatment responses
Of the environmental factors, allergic reactions remain important; evidence also suggests a key and expanding role for viral respiratory infections in these processes
The onset of asthma for most patients begins early in life, with the pattern of disease persistence determined by early, recognizable risk factors, including atopic disease, recurrent wheezing, and a parental history of asthma
Current anti-inflammatory therapy for asthma does not appear to prevent progression of the underlying disease severity

The pathophysiology of asthma is complex and involves the following components:

Airway inflammation
Intermittent airflow obstruction
Bronchial hyperresponsiveness

Airway inflammation

The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth-muscle hyperplasia, and airway remodeling are present. [2] (See the image below.)

Pathogenesis of asthma. Antigen presentation by dendritic cell with lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.

Among the principal cells identified in airway inflammation are mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines. Other constituent airway cells (eg, fibroblasts, endothelial cells, and epithelial cells) contribute to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins and integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-derived mediators influence smooth-muscle tone and produce structural changes and remodeling of the airway.

The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

A study by Balzar et al reported changes in airway resident mast cell populations from a large group of subjects with asthma and normal control subjects. [7] A greater proportion of chymase-positive mast cells in the airways and increased prostaglandin D2 levels were identified as important predictors of severe asthma as compared with other steroid-treated subjects with asthma.

Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may not be fully reversible, because of the airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease.

Airway inflammation in asthma may represent a loss of normal balance between two "opposing" populations of T helper (Th) lymphocytes. Two types of Th lymphocytes have been characterized: Th1 and Th2. Th1 cells produce IL-2 and interferon alfa, which are critical in cellular defense mechanisms against infection. Th2, in contrast, generates a family of cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation. A study by Gauvreau et al found that IL-13 has a role in allergen-induced airway responses. [8]

The so-called hygiene hypothesis of asthma illustrates how this cytokine imbalance may explain some of the dramatic increases in asthma prevalence in westernized countries. [9] This hypothesis is based on the concept that the immune system of the newborn is skewed toward Th2 cytokine generation (mediators of allergic inflammation). Following birth, environmental stimuli (eg, infections) activate Th1 responses and bring the Th1-Th2 relationship to an appropriate balance. However, support for the hygiene hypothesis has not been unequivocal. [10]

Airflow obstruction

Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucus plug formation, and airway remodeling, as follows:

Acute bronchoconstriction is the consequence of IgE-dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response
Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response
Chronic mucus plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve
Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction [11]

Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing.

Bronchial hyperresponsiveness

Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intra-alveolar pressure due to hyperinflation all lead to ventilation-perfusion (V/Q) mismatch. Vasoconstriction due to alveolar hypoxia contributes to this mismatch as well. Vasoconstriction is also considered an adaptive response to V/Q mismatch.

In the early stages, when V/Q mismatch results in hypoxia, hypercarbia is prevented by the ready diffusion of carbon dioxide across alveolar capillary membranes. Thus, patients with asthma who are in the early stages of an acute episode have hypoxemia in the absence of carbon dioxide retention. Hyperventilation triggered by the hypoxic drive also causes a decrease in arterial partial pressure of carbon dioxide (PaCO2). An increase in alveolar ventilation in the early stages of an acute exacerbation prevents hypercarbia. With worsening obstruction and increasing V/Q mismatch, carbon dioxide retention occurs.

In the early stages of an acute episode, respiratory alkalosis results from hyperventilation. Later, the increased work of breathing, increased oxygen consumption, and increased cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis due to retention of carbon dioxide as alveolar ventilation decreases.

Etiology

Factors that can contribute to asthma or airway hyperreactivity may include any of the following:

Environmental allergens (eg, house dust mites; animal allergens, especially cat and dog; cockroach allergens; and fungi)
Viral respiratory tract infections
Exercise, hyperventilation
Gastroesophageal reflux (GER) disease (GERD)
Chronic sinusitis or rhinitis
Aspirin or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, sulfite sensitivity
Use of beta-adrenergic receptor blockers (including ophthalmic preparations)
Obesity [12]
Environmental pollutants, tobacco smoke
Occupational exposure
Irritants (eg, household sprays, paint fumes)
Various high- and low-molecular-weight compounds (eg, insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and fluxes; associated with occupational asthma)
Emotional factors or stress
Perinatal factors (prematurity and increased maternal age; maternal smoking and antenatal exposure to tobacco smoke; breastfeeding has not been definitely shown to be protective)

Aspirin-induced asthma

The triad of asthma, aspirin sensitivity, and nasal polyps affects 5-10% of patients with asthma. Most patients experience symptoms during the third or fourth decade. A single dose can provoke an acute asthma exacerbation, accompanied by rhinorrhea, conjunctival irritation, and flushing of the head and neck. This reaction can also occur with other NSAIDs and is caused by an increase in eosinophils and cysteinyl leukotrienes after exposure. [13]

A study by Beasley et al demonstrated some epidemiologic evidence that exposure to acetaminophen is associated with an increased risk of asthma. [14] However, no clinical studies have directly linked asthma symptoms with acetaminophen use.

Primary treatment consists of avoiding these medications, but leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for cardiac or rheumatic disease. Aspirin desensitization has also been reported to decrease sinus symptoms, allowing daily dosing of aspirin. [15]

Gastroesophageal reflux disease

The presence of acid in the distal esophagus, mediated via vagal or other neural reflexes, can significantly increase airway resistance and airway reactivity. Patients with asthma are three times more likely also to have GERD. [16] Some people with asthma have significant GER without esophageal symptoms. In a study by Harding et al, GER was found to be a definite asthma-causing factor (defined by a favorable asthma response to medical antireflux therapy) in 64% of patients; clinically silent reflux was present in 24% of all patients. [16]

Occupational factors play a role in 10-15% of adult asthma cases. More than 300 specific occupational agents have been associated with asthma. High-risk jobs include farming, painting, janitorial work, and plastics manufacturing. In a 2008 consensus statement, the American College of Chest Physicians (ACCP) defined work-related asthma as including both occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and work-exacerbated asthma (ie, preexisting or concurrent asthma worsened by work factors). [17] The ACCP recommended consideration of work-related asthma in all patients presenting with new-onset or worsening asthma.

Two types of occupational asthma are recognized: immune-related and non-immune-related. Immune-mediated asthma has a latency of months to years after exposure. Non-immune-mediated asthma, or irritant-induced asthma (reactive airway dysfunction syndrome), has no latency period and may occur within 24 hours after an accidental exposure to high concentrations of respiratory irritants.

Careful attention must be paid to the patient's occupational history. Those with a history of asthma who report worsening of symptoms during the week and improvement during the weekends should be evaluated for occupational exposure. Peak-flow monitoring during work (optimally, ≥4 times daily) for at least 2 weeks and a similar period away from work is one recommended method of establishing the diagnosis. [17]

Viral exposure in children

Rhinoviral illness during infancy appears to be a significant risk factor for the development of wheezing in preschool children and a frequent trigger of wheezing illnesses in children with asthma. [18] Human rhinovirus (HRV) group C (HRVC) is a relatively recently identified genotype of HRV that is found in patients with respiratory tract infections. A study of children with acute asthma who presented to the emergency department (ED) found that HRVC was present in the majority and that the presence of HRVC was associated with more severe asthma. [19]

Approximately 80-85% of childhood asthma episodes are associated with prior viral exposure. Previous childhood pneumonia due to infection by respiratory syncytial virus (RSV), Mycoplasma pneumoniae, or Chlamydia species was found in more than 50% of a small sample of children aged 7-9 years who later had asthma. [20] Treatment with antibiotics appropriate for these organisms improves the clinical signs and symptoms of asthma.

Sinusitis

Of patients with asthma, 50% have concurrent sinus disease. Sinusitis is the most important exacerbating factor for asthma symptoms. Either acute infectious sinus disease or chronic inflammation may contribute to worsening airway symptoms. Treatment of nasal and sinus inflammation reduces airway reactivity. Treatment of acute sinusitis requires at least 10 days of antibiotics to improve asthma symptoms. [21]

Exercise-induced bronchoconstriction

Exercise-induced bronchoconstriction (EIB; also referred to as exercise-induced asthma [EIA]) is a condition in which exercise or vigorous physical activity triggers acute bronchoconstriction in persons with heightened airway reactivity. It is observed primarily in persons who have asthma but can also be found in patients with normal resting spirometry findings with atopy, allergic rhinitis, or cystic fibrosis, and even in healthy persons, many of whom are elite or cold-weather athletes. EIB is often a neglected diagnosis, and the underlying condition may be silent in as many as 50% of patients, except during exercise. [22, 23]

The pathogenesis of EIB is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of the two. The upper airway functions to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage (BAL) studies have not demonstrated an increase in inflammatory mediators.

These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

Factors that contribute to EIB symptoms (in both persons with asthma and nonasthmatic athletes) include the following:

Exposure to cold or dry air
Environmental pollutants (eg, sulfur, ozone)
Level of bronchial hyperreactivity
Chronicity of asthma and symptomatic control
Duration and intensity of exercise
Allergen exposure in atopic individuals
Coexisting respiratory infection

The diagnosis of EIB is made more often in children and young adults than in older adults and is related to high levels of physical activity. EIB can be observed in persons of any age, depending on the level of underlying airway reactivity and the level of physical exertion.

Genetics

Research on genetic mutations casts further light on the synergistic nature of multiple mutations in the pathophysiology of asthma. Polymorphisms in the gene that encodes platelet-activating factor (PAF) acetylhydrolase (PAF-AH), an intrinsic neutralizing agent of PAF in most humans, may play a role in susceptibility to asthma and asthma severity. [24]

Evidence suggests that the prevalence of asthma is reduced in association with the following:

Certain infections (Mycobacterium tuberculosis, measles, or hepatitis A)
Rural living
Exposure to other children (eg, presence of older siblings and early enrollment in childcare)
Less frequent use of antibiotics

Furthermore, the absence of these lifestyle events is associated with the persistence of a Th2 cytokine pattern. Under these conditions, the genetic background of the child, with a cytokine imbalance toward Th2, sets the stage to promote the production of IgE to key environmental antigens (eg, dust mites, cockroaches, Alternaria, and possibly cats). Therefore, a gene-by-environment interaction occurs in which the susceptible host is exposed to environmental factors that are capable of generating IgE, and sensitization occurs.

A reciprocal interaction is apparent between the two Th subpopulations, in which Th1 cytokines can inhibit Th2 generation and vice versa. Allergic inflammation may be the result of an excessive expression of Th2 cytokines. Alternatively, it has been suggested that the loss of normal immune balance arises from a cytokine dysregulation in which Th1 activity in asthma is diminished. [25]

Several studies have highlighted the importance of genotypes in children's susceptibility to asthma and response to specific antiasthma medications. [26, 27, 28]

Obesity

In a study exploring the relationships between asthma, obesity, and abnormal lipid and glucose metabolism, Cottrell et al found that community-based data linked asthma, body mass, and metabolic variables in children. [29] Specifically, these findings described a statistically significant association between asthma and abnormal lipid and glucose metabolism beyond body mass association. There is growing evidence to suggest that individuals with a high body mass index (BMI) have worse asthma control and sustained weight loss improves asthma control. [30]

Accelerated weight gain in early infancy is associated with increased risks of asthma symptoms, according to one study of preschool children. [31]

Epidemiology

US and international statistics

In the United States, asthma has been estimated to affect 26.8 million persons (8.2%), including 4.5 million children (6.2%). [1] The overall prevalence of EIB is 3-10% of the general population if persons who do not have asthma or allergy are excluded but rises to 12-15% if patients with underlying asthma are included.

Asthma has been estimated to affect as many as 300 million individuals worldwide. [32] A study using data from the Global Burden of Disease (GBD) study reported that in 2021, asthma affected 260.48 million individuals, approximately 436,190 asthma deaths occurred, and 21.42 million disability-adjusted life-years (DALYs) were lost because of asthma. [33]

Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where many of the asthma data have been collected. The prevalence of severe asthma in industrialized countries ranges from 2% to 10%. Trends have suggested increases in both the prevalence and the morbidity of asthma, especially in children younger than 6 years. Factors that have been implicated include urbanization, air pollution, passive smoking, and change in exposure to environmental allergens.

Asthma prevalence is higher in very young persons and very old persons because of airway responsiveness and lower levels of lung function. [34] Two thirds of all asthma cases are diagnosed before the patient is aged 18 years. Approximately half of all children diagnosed with asthma have a decrease or disappearance of symptoms by early adulthood. [35]

Asthma predominantly occurs in boys in childhood, with a male-to-female ratio of 2:1 until puberty, when the male-to-female ratio becomes 1:1. Asthma prevalence is greater in females after puberty, and the majority of adult-onset cases diagnosed in persons older than 40 years occur in females. Boys are more likely than girls to experience a decrease in symptoms by late adolescence.

In the United States, asthma prevalence, as well as morbidity and mortality, is higher in Blacks than in Whites. Although genetic factors are of major importance in determining a predisposition to the development of asthma, environmental factors play a greater role than racial factors in asthma onset. A national concern is that some of the increased morbidity is due to differences in asthma treatment afforded certain minority groups. Larger asthma-associated lung function deficits are reported in Hispanics, especially females. [36]

Prognosis

In 2021, US asthma mortality was reported to be 10.6 deaths per million persons. [1] International asthma mortality has been reported to be as high as 0.86 deaths per 100,000 persons in some countries.

Mortality is primarily related to lung function, with an eightfold increase in patients in the lowest quartile, but it has also been linked with asthma management failure, especially in young persons. Other factors that impact mortality include age older than 40 years, cigarette smoking more than 20 pack-years, blood eosinophilia, forced expiratory volume in one second (FEV1) 40-69% of predicted, and greater reversibility. [37]

The estimate of lost work and school time from asthma is approximately 100 million days of restricted activity. In 2020, there were 986,453 ED visits for asthma and 94,560 hospitalizations. [1] For 2021-2022, the annual expenditures for healthcare utilization due to asthma and COPD amounted to an estimated $32.7 billion. [38]

Nearly one half of children diagnosed with asthma will have a decrease in symptoms and require less treatment by late adolescence or early adulthood. In a study of 900 children with asthma, 6% required no treatment after 1 year, and 39% only required intermittent treatment.

Patients with poorly controlled asthma develop long-term changes over time (ie, with airway remodeling). This can lead to chronic symptoms and a significant irreversible component to their disease. Many patients who develop asthma at an older age also tend to have chronic symptoms.

Patient Education

The need for patient education about asthma and the establishment of a partnership between patient and clinician in the management of the disease was emphasized by the NAEPP in its updated 2020 guidelines. [5]

The key points of education include the following:

Patient education (see the video below) should be integrated into every aspect of asthma care
All members of the healthcare team, including nurses, pharmacists, and respiratory therapists, should provide education
Clinicians should teach patients asthma self-management based on basic asthma facts, self-monitoring techniques, the role of medications, inhaler use, and environmental control measures [39, 40, 41]
Treatment goals should be developed for the patient and family
A written, individualized, daily self-management plan should be developed
Several well-validated asthma action plans are now available and are key in the management of asthma and should therefore be reviewed, including the Asthma Control Test (ACT), the Asthma Therapy Assessment Questionnaire (ATAQ), and the Asthma Control Questionnaire (ACQ) [42]

Asthma is characterized by chronic inflammation and asthma exacerbations, where environmental trigger initiates inflammation, which makes it difficult to breathe. This video covers pathophysiology of asthma, signs and symptoms, types, and treatment.

School-based asthma education programs improved knowledge of asthma, self-efficacy, and self-management behaviors in children aged 4-17 years, according to a systematic literature review by Coffman et al, but the programs had less effect on quality of life, days of symptoms, nights with symptoms, and school absences. [43]

The 2025 Veterans Administration/Department of Defense (VA/DoD) clinical practice guideline for primary care management of asthma concurred with the NAEPP in recommending self-management education for both the patient and caregiver as part of the treatment program. [44]

Most recent national asthma data. Centers for Disease Control and Prevention. Available athttps://www.cdc.gov/asthma-data/about/most-recent-asthma-data.html. November 21, 2024; Accessed: January 16, 2026.
Han X, Krempski JW, Nadeau K. Advances and novel developments in mechanisms of allergic inflammation. Allergy. 2020 Dec. 75 (12):3100-3111. [QxMD MEDLINE Link].
Chung KF, Adcock IM. Precision medicine for the discovery of treatable mechanisms in severe asthma. Allergy. 2019 Sep. 74 (9):1649-1659. [QxMD MEDLINE Link].
Cevhertas L, Ogulur I, Maurer DJ, Burla D, Ding M, Jansen K, et al. Advances and recent developments in asthma in 2020. Allergy. 2020 Dec. 75 (12):3124-3146. [QxMD MEDLINE Link].
[Guideline] 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), 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. 2020 Dec. 146 (6):1217-1270. [QxMD MEDLINE Link].[Full Text].
Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A, et al. Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Lancet Respir Med. 2019 May. 7 (5):402-416. [QxMD MEDLINE Link].
Balzar S, Fajt ML, Comhair SA, Erzurum SC, Bleecker E, Busse WW, et al. Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. Am J Respir Crit Care Med. 2011 Feb 1. 183 (3):299-309. [QxMD MEDLINE Link].[Full Text].
Gauvreau GM, Boulet LP, Cockcroft DW, Fitzgerald JM, Carlsten C, Davis BE, et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med. 2011 Apr 15. 183 (8):1007-14. [QxMD MEDLINE Link].
Anderson WJ, Watson L. Asthma and the hygiene hypothesis. N Engl J Med. 2001 May 24. 344 (21):1643-4. [QxMD MEDLINE Link].
Brooks C, Pearce N, Douwes J. The hygiene hypothesis in allergy and asthma: an update. Curr Opin Allergy Clin Immunol. 2013 Feb. 13 (1):70-7. [QxMD MEDLINE Link].
Sears MR. Consequences of long-term inflammation. The natural history of asthma. Clin Chest Med. 2000 Jun. 21 (2):315-29. [QxMD MEDLINE Link].
Camargo CA Jr, Weiss ST, Zhang S, Willett WC, Speizer FE. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Arch Intern Med. 1999 Nov 22. 159 (21):2582-8. [QxMD MEDLINE Link].
Henderson WR Jr. Role of leukotrienes in asthma. Ann Allergy. 1994 Mar. 72 (3):272-8. [QxMD MEDLINE Link].
Beasley RW, Clayton TO, Crane J, Lai CK, Montefort SR, Mutius Ev, et al. Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three. Am J Respir Crit Care Med. 2011 Jan 15. 183 (2):171-8. [QxMD MEDLINE Link].
Comert S, Karakaya G. Kalyoncu AF. Aspirin desensitization treatment for the management of aspirin-exacerbated respiratory disease. J Respir Res. 2016. 2:24-7.
Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med. 2000 Jul. 162 (1):34-9. [QxMD MEDLINE Link].
Tarlo SM, Balmes J, Balkissoon R, Beach J, Beckett W, Bernstein D, et al. Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. Chest. 2008 Sep. 134 (3 Suppl):1S-41S. [QxMD MEDLINE Link].
Lemanske RF Jr, Jackson DJ, Gangnon RE, Evans MD, Li Z, Shult PA, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005 Sep. 116 (3):571-7. [QxMD MEDLINE Link].
Bizzintino J, Lee WM, Laing IA, Vang F, Pappas T, Zhang G, et al. Association between human rhinovirus C and severity of acute asthma in children. Eur Respir J. 2011 May. 37 (5):1037-42. [QxMD MEDLINE Link].[Full Text].
Martin RJ, Kraft M, Chu HW, Berns EA, Cassell GH. A link between chronic asthma and chronic infection. J Allergy Clin Immunol. 2001 Apr. 107 (4):595-601. [QxMD MEDLINE Link].
Hamilos DL. Gastroesophageal reflux and sinusitis in asthma. Clin Chest Med. 1995 Dec. 16 (4):683-97. [QxMD MEDLINE Link].
McFadden ER Jr. Exercise-induced airway obstruction. Clin Chest Med. 1995 Dec. 16 (4):671-82. [QxMD MEDLINE Link].
Randolph C. Exercise-induced asthma: update on pathophysiology, clinical diagnosis, and treatment. Curr Probl Pediatr. 1997 Feb. 27 (2):53-77. [QxMD MEDLINE Link].
Ito S, Noguchi E, Shibasaki M, Yamakawa-Kobayashi K, Watanabe H, Arinami T. Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma. J Hum Genet. 2002. 47 (2):99-101. [QxMD MEDLINE Link].
Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000 May. 161 (5):1720-45. [QxMD MEDLINE Link].
Drazen JM, Yandava CN, Dubé L, Szczerback N, Hippensteel R, Pillari A, et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999 Jun. 22 (2):168-70. [QxMD MEDLINE Link].
Thompson EE, Pan L, Ostrovnaya I, Weiss LA, Gern JE, Lemanske RF Jr, et al. Integrin beta 3 genotype influences asthma and allergy phenotypes in the first 6 years of life. J Allergy Clin Immunol. 2007 Jun. 119 (6):1423-9. [QxMD MEDLINE Link].
Wechsler ME, Lehman E, Lazarus SC, Lemanske RF Jr, Boushey HA, Deykin A, et al. beta-Adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care Med. 2006 Mar 1. 173 (5):519-26. [QxMD MEDLINE Link].[Full Text].
Cottrell L, Neal WA, Ice C, Perez MK, Piedimonte G. Metabolic abnormalities in children with asthma. Am J Respir Crit Care Med. 2011 Feb 15. 183 (4):441-8. [QxMD MEDLINE Link].[Full Text].
Juel CT, Ali Z, Nilas L, Ulrik CS. Asthma and obesity: does weight loss improve asthma control? a systematic review. J Asthma Allergy. 2012. 5:21-6. [QxMD MEDLINE Link].
Sonnenschein-van der Voort AM, Jaddoe VW, Raat H, Moll HA, Hofman A, de Jongste JC, et al. Fetal and infant growth and asthma symptoms in preschool children: the Generation R Study. Am J Respir Crit Care Med. 2012 Apr 1. 185 (7):731-7. [QxMD MEDLINE Link].
[Guideline] Global strategy for asthma management and prevention, 2025. Global Initiative for Asthma. Available athttps://ginasthma.org/wp-content/uploads/2025/11/GINA-2025-Update-25_11_08-WMS.pdf. November 15, 2025; Accessed: January 16, 2026.
Zhang L, Jiang H, Yang G, Zhang J, Yuan S, Chen J, et al. Global, regional and national burden of asthma from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021. BMJ Open Respir Res. 2025 Jul 23. 12 (1):143-78. [QxMD MEDLINE Link].[Full Text].
Burrows B, Barbee RA, Cline MG, Knudson RJ, Lebowitz MD. Characteristics of asthma among elderly adults in a sample of the general population. Chest. 1991 Oct. 100 (4):935-42. [QxMD MEDLINE Link].
Martin AJ, Landau LI, Phelan PD. Lung function in young adults who had asthma in childhood. Am Rev Respir Dis. 1980 Oct. 122 (4):609-16. [QxMD MEDLINE Link].
Zhang Y, McConnell R, Gilliland F, Berhane K. Ethnic differences in the effect of asthma on pulmonary function in children. Am J Respir Crit Care Med. 2011 Mar 1. 183 (5):596-603. [QxMD MEDLINE Link].[Full Text].
Sly RM. Changing asthma mortality. Ann Allergy. 1994 Sep. 73 (3):259-68. [QxMD MEDLINE Link].
Aggregate cost of care and healthcare utilization. National Heart, Lung, and Blood Institute. Available athttps://www.nhlbi.nih.gov/research/data/healthcare-costs. 2021-2022; Accessed: January 16, 2026.
Bailey WC, Richards JM Jr, Brooks CM, Soong SJ, Windsor RA, Manzella BA. A randomized trial to improve self-management practices of adults with asthma. Arch Intern Med. 1990 Aug. 150 (8):1664-8. [QxMD MEDLINE Link].
Ignacio-Garcia JM, Gonzalez-Santos P. Asthma self-management education program by home monitoring of peak expiratory flow. Am J Respir Crit Care Med. 1995 Feb. 151 (2 Pt 1):353-9. [QxMD MEDLINE Link].
Kotses H, Bernstein IL, Bernstein DI, Reynolds RV, Korbee L, Wigal JK, et al. A self-management program for adult asthma. Part I: Development and evaluation. J Allergy Clin Immunol. 1995 Feb. 95 (2):529-40. [QxMD MEDLINE Link].
Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004 Jan. 113 (1):59-65. [QxMD MEDLINE Link].
Coffman JM, Cabana MD, Yelin EH. Do school-based asthma education programs improve self-management and health outcomes?. Pediatrics. 2009 Aug. 124 (2):729-42. [QxMD MEDLINE Link].[Full Text].
[Guideline] VA/DoD clinical practice guideline for the primary care management of asthma. Version 4.0 - 2025. Department of Veterans Affairs/Department of Defense. Available athttps://www.healthquality.va.gov/HEALTHQUALITY/guidelines/CD/asthma/Asthma-CPG_2025-Guideline_final_20250528.pdf. March 2025; Accessed: February 5, 2026.
Font-Ribera L, Villanueva CM, Nieuwenhuijsen MJ, Zock JP, Kogevinas M, Henderson J. Swimming pool attendance, asthma, allergies, and lung function in the Avon Longitudinal Study of Parents and Children cohort. Am J Respir Crit Care Med. 2011 Mar 1. 183 (5):582-8. [QxMD MEDLINE Link].[Full Text].
[Guideline] Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020 Jan. 55 (1):343-73. [QxMD MEDLINE Link].[Full Text].
[Guideline] Global Asthma Network. The Global Asthma Report 2022. Int J Tuberc Lung Dis. 2022 Nov 25. 26 (Supp 1):1-104. [QxMD MEDLINE Link].[Full Text].
Shao W, Chung T, Berdon WE, Mellins RB, Griscom NT, Ruzal-Shapiro C, et al. Fluoroscopic diagnosis of laryngeal asthma (paradoxical vocal cord motion). AJR Am J Roentgenol. 1995 Nov. 165 (5):1229-31. [QxMD MEDLINE Link].
Morris MJ, Deal LE, Bean DR, Grbach VX, Morgan JA. Vocal cord dysfunction in patients with exertional dyspnea. Chest. 1999 Dec. 116 (6):1676-82. [QxMD MEDLINE Link].
Nastasi KJ, Howard DA, Raby RB, Lew DB, Blaiss MS. Airway fluoroscopic diagnosis of vocal cord dysfunction syndrome. Ann Allergy Asthma Immunol. 1997 Jun. 78 (6):586-8. [QxMD MEDLINE Link].
Wynn SR, O'Connell EJ, Frigas E, Payne WS, Sachs MI. Exercise-induced "asthma" as a presentation of bronchial carcinoid. Ann Allergy. 1986 Aug. 57 (2):139-41. [QxMD MEDLINE Link].
Rolfe LM, Rayner CF. A wheezy man with a bony abnormality. Postgrad Med J. 1999 Aug. 75 (886):503-4. [QxMD MEDLINE Link].[Full Text].
Kim YW, Han SK, Shim YS, Kim KY, Han YC, Seo JW, et al. The first report of diffuse panbronchiolitis in Korea: five case reports. Intern Med. 1992 May. 31 (5):695-701. [QxMD MEDLINE Link].
Bevelaqua F, Schicchi JS, Haas F, Axen K, Levin N. Aortic arch anomaly presenting as exercise-induced asthma. Am Rev Respir Dis. 1989 Sep. 140 (3):805-8. [QxMD MEDLINE Link].
Newman LJ, Platts-Mills TA, Phillips CD, Hazen KC, Gross CW. Chronic sinusitis. Relationship of computed tomographic findings to allergy, asthma, and eosinophilia. JAMA. 1994 Feb 2. 271 (5):363-7. [QxMD MEDLINE Link].
Shapiro GG, Christie DL. Gastroesophageal reflux and asthma. Clin Rev Allergy. 1983 Mar. 1 (1):39-56. [QxMD MEDLINE Link].
Cuevas Hernández MM, Arias Hernández RM. [Pulmonary gammagraphy study in asthmatic children with gastroesophageal reflux]. Rev Alerg Mex. 2008 Nov-Dec. 55 (6):229-33. [QxMD MEDLINE Link].
Bacci E, Cianchetti S, Bartoli M, Dente FL, Di Franco A, Vagaggini B, et al. Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients. Chest. 2006 Mar. 129 (3):565-72. [QxMD MEDLINE Link].
Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30. 360 (9347):1715-21. [QxMD MEDLINE Link].
Ravindran S, Kaleem Ullah M, Karnik M, Greeshma MV, Bansal N, Kulkarni S, et al. Unsupervised Phenotyping of Asthma: Integrating Serum Periostin with Clinical and Inflammatory Profiles. Diagnostics (Basel). 2025 Nov 27. 15 (23):[QxMD MEDLINE Link].[Full Text].
Mena AH, Garijo MAG, Abejón VDP, Vidigal FFR. Changes in serum periostin levels in uncontrolled asthma in children (DADO phase 2 study). Allergol Immunopathol (Madr). 2025. 53 (1):1-7. [QxMD MEDLINE Link].
Matsumoto H. Serum periostin: a novel biomarker for asthma management. Allergol Int. 2014 Jun. 63 (2):153-60. [QxMD MEDLINE Link].
Szefler S, Corren J, Silverberg JI, Okragly A, Sun Z, Natalie CR, et al. Lebrikizumab decreases type 2 inflammatory biomarker levels in patients with asthma: data from randomized phase 3 trials (LAVOLTA I and II). Immunotherapy. 2024. 16 (20-22):1211-1216. [QxMD MEDLINE Link].[Full Text].
Woods AQ, Lynch DA. Asthma: an imaging update. Radiol Clin North Am. 2009 Mar. 47 (2):317-29. [QxMD MEDLINE Link].
Teel GS, Engeler CE, Tashijian JH, duCret RP. Imaging of small airways disease. Radiographics. 1996 Jan. 16 (1):27-41. [QxMD MEDLINE Link].
Rossi OV, Lähde S, Laitinen J, Huhti E. Contribution of chest and paranasal sinus radiographs to the management of acute asthma. Int Arch Allergy Immunol. 1994 Sep. 105 (1):96-100. [QxMD MEDLINE Link].
Enright PL, Lebowitz MD, Cockroft DW. Physiologic measures: pulmonary function tests. Asthma outcome. Am J Respir Crit Care Med. 1994 Feb. 149 (2 Pt 2):S9-18; discussion S19-20. [QxMD MEDLINE Link].
Ali SS, O'Connell C, Kass L, Graff G. Single-breath counting: a pilot study of a novel technique for measuring pulmonary function in children. Am J Emerg Med. 2011 Jan. 29 (1):33-6. [QxMD MEDLINE Link].
Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan. 161 (1):309-29. [QxMD MEDLINE Link].
Anderson SD, Charlton B, Weiler JM, Nichols S, Spector SL, Pearlman DS, et al. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res. 2009 Jan 23. 10 (1):4. [QxMD MEDLINE Link].
Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med. 2005 May 26. 352 (21):2163-73. [QxMD MEDLINE Link].
Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan. 129 (1 Suppl):80S-94S. [QxMD MEDLINE Link].
Aras G, Kanmaz D, Kadakal F, Purisa S, Sonmez K, Tuncay E, et al. Gastroesophageal reflux disease in our asthma patients: the presence of dysphagia can influence pulmonary function. Multidiscip Respir Med. 2012 Dec 17. 7 (1):53. [QxMD MEDLINE Link].
[Guideline] Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013 May 1. 187 (9):1016-27. [QxMD MEDLINE Link].
[Guideline] Nakamura Y, Tamaoki J, Nagase H, Yamaguchi M, Horiguchi T, Hozawa S, et al. Japanese guidelines for adult asthma 2020. Allergol Int. 2020 Oct. 69 (4):519-548. [QxMD MEDLINE Link].
Scott M, Roberts G, Kurukulaaratchy RJ, Matthews S, Nove A, Arshad SH. Multifaceted allergen avoidance during infancy reduces asthma during childhood with the effect persisting until age 18 years. Thorax. 2012 Dec. 67 (12):1046-51. [QxMD MEDLINE Link].
McCormack MC, Breysse PN, Matsui EC, Hansel NN, Peng RD, Curtin-Brosnan J, et al. Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma. Ann Allergy Asthma Immunol. 2011 Apr. 106 (4):308-15. [QxMD MEDLINE Link].
Sheikh A, Hurwitz B, Shehata Y. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev. 2007 Jan 24. CD001563. [QxMD MEDLINE Link].
Tung KY, Tsai CH, Lee YL. Microsomal epoxide hydroxylase genotypes/diplotypes, traffic air pollution, and childhood asthma. Chest. 2011 Apr. 139 (4):839-848. [QxMD MEDLINE Link].
Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med. 1992 Jul. 10 (4):301-10. [QxMD MEDLINE Link].
Rowe BH, Edmonds ML, Spooner CH, Diner B, Camargo CA Jr. Corticosteroid therapy for acute asthma. Respir Med. 2004 Apr. 98 (4):275-84. [QxMD MEDLINE Link].
Tantisira KG, Lasky-Su J, Harada M, Murphy A, Litonjua AA, Himes BE, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011 Sep 29. 365 (13):1173-83. [QxMD MEDLINE Link].
Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010 Oct 28. 363 (18):1715-26. [QxMD MEDLINE Link].[Full Text].
Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27. 367 (13):1198-207. [QxMD MEDLINE Link].
Rank MA, Liesinger JT, Ziegenfuss JY, Branda ME, Lim KG, Yawn BP, et al. The impact of asthma medication guidelines on asthma controller use and on asthma exacerbation rates comparing 1997-1998 and 2004-2005. Ann Allergy Asthma Immunol. 2012 Jan. 108 (1):9-13. [QxMD MEDLINE Link].
Marcus P. Incorporating anti-IgE (omalizumab) therapy into pulmonary medicine practice: practice management implications. Chest. 2006 Feb. 129 (2):466-474. [QxMD MEDLINE Link].
Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011 Mar 17. 364 (11):1005-15. [QxMD MEDLINE Link].[Full Text].
Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes-Rivera I, Zhu J, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011 May 3. 154 (9):573-82. [QxMD MEDLINE Link].
Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25. 371 (13):1198-207. [QxMD MEDLINE Link].[Full Text].
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25. 371 (13):1189-97. [QxMD MEDLINE Link].[Full Text].
Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18. 380 (9842):651-9. [QxMD MEDLINE Link].
Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May. 3 (5):355-66. [QxMD MEDLINE Link].
Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011 Nov 15. 184 (10):1125-32. [QxMD MEDLINE Link].[Full Text].
Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29. 388 (10056):2115-2127. [QxMD MEDLINE Link].
FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29. 388 (10056):2128-2141. [QxMD MEDLINE Link].
Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22. 376 (25):2448-2458. [QxMD MEDLINE Link].
Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018 Jun 28. 378 (26):2486-2496. [QxMD MEDLINE Link].
Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018 Jun 28. 378 (26):2475-2485. [QxMD MEDLINE Link].
Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13. 384 (19):1800-1809. [QxMD MEDLINE Link].[Full Text].
Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, et al. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017 Sep 7. 377 (10):936-946. [QxMD MEDLINE Link].[Full Text].
Zecchin C, Schalkwijk S, Pouliquen IJ, Berges A, Bird N, Follows R, et al. Straight to Phase III: Model-Informed Approach Speeds Depemokimab Clinical Development in Interleukin-5-Driven Diseases. Clin Pharmacol Ther. 2026 Jan 20. [QxMD MEDLINE Link].
Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010 Aug 4. CD001186. [QxMD MEDLINE Link].
Brüggenjürgen B, Reinhold T, Brehler R, Laake E, Wiese G, Machate U, et al. Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma. Ann Allergy Asthma Immunol. 2008 Sep. 101 (3):316-24. [QxMD MEDLINE Link].
Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010 Jan 15. 181 (2):116-24. [QxMD MEDLINE Link].
Wechsler ME, Laviolette M, Rubin AS, Fiterman J, Lapa e Silva JR, Shah PL, et al. Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013 Dec. 132 (6):1295-302. [QxMD MEDLINE Link].
O'Byrne PM, Pedersen S, Carlsson LG, Radner F, Thorén A, Peterson S, et al. Risks of pneumonia in patients with asthma taking inhaled corticosteroids. Am J Respir Crit Care Med. 2011 Mar 1. 183 (5):589-95. [QxMD MEDLINE Link].
Dhuper S, Chandra A, Ahmed A, Bista S, Moghekar A, Verma R, et al. Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma treatment. J Emerg Med. 2011 Mar. 40 (3):247-55. [QxMD MEDLINE Link].
Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000 Oct 12. 343 (15):1064-9. [QxMD MEDLINE Link].
Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11. 354 (19):1985-97. [QxMD MEDLINE Link].
Sigelko AD, Strek ME, Wolfe KS. Asthma in Pregnancy. Obstet Gynecol. 2025 Jun 5. 146 (1):39-58. [QxMD MEDLINE Link].[Full Text].
[Guideline] Dombrowski MP, Schatz M, ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 90, February 2008: asthma in pregnancy. Obstet Gynecol. 2008 Feb. 111 (2 Pt 1):457-64. [QxMD MEDLINE Link].
van den Berge M, Ten Hacken NHT, Cohen J, Douma WR, Postma DS. Small airway disease in asthma and COPD: clinical implications. Chest. 2011 Feb. 139 (2):412-423. [QxMD MEDLINE Link].
Kingston HG, Hirshman CA. Perioperative management of the patient with asthma. Anesth Analg. 1984 Sep. 63 (9):844-55. [QxMD MEDLINE Link].
Scott HA, Gibson PG, Garg ML, Pretto JJ, Morgan PJ, Callister R, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy. 2013 Jan. 43 (1):36-49. [QxMD MEDLINE Link].
[Guideline] British Thoracic Society (BTS), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN). BTS/NICE/SIGN joint guideline on asthma: diagnosis, monitoring and chronic asthma management (November 2024) - summary of recommendations. Thorax. 2025 Jun 16. 80 (7):416-424. [QxMD MEDLINE Link].[Full Text].

Author

Michael J Morris, MD, FACP, FCCP Clinical Faculty, Pulmonary Disease/Critical Care Service, Department of Medicine, Brooke Army Medical Center; Assistant Dean for Research, SAUSHEC, Brooke Army Medical Center; Clinical Professor, niversity of Texas Health Science Center at San Antonio, Joe R and Teresa Lozano Long School of Medicine; Professor, Uniformed Services University of the Health Sciences

Michael J Morris, MD, FACP, FCCP is a member of the following medical societies: American Association for Respiratory Care, American College of Chest Physicians, American College of Physicians, The Society of Federal Health Professionals (AMSUS)