Trigger control to enhance asthma management

INTRODUCTION — Asthma is a chronic lung disease characterized by airway obstruction, inflammation, and hyperresponsiveness [1,2]. A broad range of factors have been identified that can make asthma worse. These factors are often referred to as "asthma triggers." Trigger exposure may occur on a chronic or episodic basis. Identifying and avoiding asthma "triggers" are essential to preventing asthma flare-ups.

A description of factors that may contribute to asthma severity and suggestions for mitigation of these factors will be reviewed here. A general approach to asthma management is provided separately. (See "An overview of asthma management".)

APPROACH TO THE PATIENT — Asthma "triggers" are often thought of as airborne agents that can bring on an attack, but a variety of other exposures can cause or exacerbate symptoms, including the following categories of stimuli [1,2]:

●Respiratory infections (viruses, bacteria)

●Allergen exposure (inhalant, food, and occupational)

●Inhaled respiratory irritants (including tobacco and cannabis [marijuana] smoke and cold, dry air)

●Temperature and weather

●Physical activity

●Hormonal fluctuations

●Medications

●Emotional factors (eg, anxiety, stress)

Comorbidities, such as rhinitis, rhinovirus infection, gastroesophageal reflux, obesity, obstructive sleep apnea, depression, and anxiety, can trigger asthma symptoms as well [2].

The initial step toward managing asthma by reducing exposure to triggers is to assess patients for a range of factors that can make asthma worse (table 1) [1,2]. Such assessment should take into account the intensity and duration of exposure, the patient's sensitivity to the agents encountered, and the clinical significance of the exposure/sensitivity in the context of the person's medical history [1]. Exposures at home, daycare, school, work, and regular leisure sites should be reviewed. Questions about work environment are particularly important as industrial or occupational exposures are responsible for 10 to 25 percent of cases of adult asthma [3].

After identification of potential asthma triggers in an individual, a plan can be devised with the patient or caregiver to enable them to reduce the exposure. Multicomponent interventions have yielded more evidence of success than single-component ones. For patients with predictable exposures to avoidable triggers, the following interventions may be useful [1]:

●Complete avoidance of the trigger (eg, mop or wet wipe instead of sweeping or dusting and consider dust mite proof encasings) as part of a multicomponent allergen mitigation intervention.

●For individuals with asthma who are exposed to cockroaches or mice in the home and who have allergy symptoms or demonstrated sensitization to these allergens, integrated pest management, used alone or with other interventions, may reduce exposure to pest-related allergens in the home.

●Limit exposure to the trigger if it cannot be completely avoided (eg, leave the room if someone starts smoking, move to another seat if someone with strong perfume sits near you, have someone else clean the house if you are allergic to indoor antigens).

●Take an extra two puffs of a short-acting bronchodilator or an antihistamine prior to exposure to an unavoidable trigger. This approach should be implemented only if the first two options are not feasible. Patients should consult with their clinician to be sure before instituting this approach, and they should be careful not to exceed the amount of normally prescribed medication.

In addition to identifying asthma triggers, clinicians should be vigilant for comorbid conditions in patients with poorly controlled asthma, particularly when typical asthma triggers do not appear to be contributing. Conditions that can contribute to or mimic asthma symptoms include a broad spectrum of processes, such as rhinosinusitis, obesity, deconditioning, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis, paroxysmal vocal fold dysfunction, gastroesophageal reflux, sleep apnea, and mechanical restriction. These conditions are reviewed separately:

●(See "Evaluation of wheezing in infants and children".)

●(See "Chronic obstructive pulmonary disease: Diagnosis and staging".)

●(See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

●(See "Gastroesophageal reflux and asthma".)

●(See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)

●(See "An overview of rhinitis".)

●(See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

●(See "Inducible laryngeal obstruction (paradoxical vocal fold motion)".)

RESPIRATORY INFECTIONS — Respiratory infections are major contributors to asthma exacerbations, and a variety of respiratory infections have been implicated, including the common cold (particularly rhinovirus), influenza, respiratory syncytial virus, human metapneumovirus, sinus infections, and pneumonia [4-7]. However, the exact mechanism(s) by which infections trigger asthma exacerbations is unclear. Possibilities include airway inflammation with neutrophils [8] or eosinophils [9], alterations in airway receptors [10,11], and increased mucosal permeability to allergens [12]. Asthma flares that occur with a respiratory infection are frequently more severe than those caused by other triggers.

Several studies have noted clusters of asthma emergency department visits and hospitalizations occurring predictably after the return to school following summer vacation and other breaks [13,14]. Specifically, there was a "September asthma epidemic" approximately 18 days after Labor Day, with a lesser increase in attacks two days later in preschool children and six days later in adults [13]. Viral infections were the presumed cause, although allergen-induced inflammation (possibly exacerbated by the viral infection) may contribute [15]. In a study of urban children with uncontrolled allergic asthma, treatment with omalizumab reduced seasonal exacerbations in the fall and spring, possibly by improving interferon alpha-mediated antiviral defenses [16,17] and/or decreasing viral shedding and duration of infections, although the exact mechanism is not known [18].

Studies have been mixed regarding the role of atypical bacteria, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, in causing asthma exacerbations and persistent asthma symptoms [19,20]. In a series of 31 children with persistent asthma, no relationship was found between detection of M. pneumoniae community-acquired respiratory distress syndrome toxin in respiratory secretions and worsening asthma [21].

For patients with poor asthma control, it is prudent to evaluate for possible contributions from chronic rhinosinusitis and allergic bronchopulmonary aspergillosis. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Relationships between rhinosinusitis and asthma" and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

Mitigating the effects of viral infection — For patients with asthma who have high-risk features (eg, required oral glucocorticoids in the past year or currently need hospitalization) and suspected or confirmed influenza infection, antiviral therapy may be indicated. The oral agent oseltamivir is preferred over the inhaled agent zanamivir, which has been associated with bronchoconstriction. The timing of treatment and choice of antiviral agents are discussed separately. (See "Seasonal influenza in children: Management", section on 'Antiviral therapy' and "Seasonal influenza in nonpregnant adults: Treatment".)

There are no available antiviral therapies for rhinovirus infection, and symptomatic therapies to reduce nasal congestion, postnasal drip, fever, or cough have not been demonstrated to reduce the likelihood of asthma exacerbation.

For adults with increasing asthma symptoms in the setting of a presumed viral infection, quadrupling the dose of inhaled glucocorticoids is controversial and not established as helping in preventing the development of an asthma exacerbation [7]. The mechanism underlying protection of virus-induced asthma exacerbations by inhaled glucocorticoids is unclear, although some reports suggest that inhaled glucocorticoids are able to reduce airway eosinophils that develop after infections. (See "Acute exacerbations of asthma in adults: Home and office management", section on 'Quadrupling the dose of inhaled glucocorticoid'.)

Data supporting the use of leukotriene antagonists in presumed virus-related asthma exacerbations are also mixed. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Leukotriene receptor antagonists'.)

Prevention — The main strategies for prevention of respiratory viral infections are careful attention to hand hygiene (table 2), avoidance of people with infections when possible, adequate amounts of sleep, and vaccination against seasonal influenza and pneumococcal infection. (See "The common cold in children: Management and prevention", section on 'Prevention' and "The common cold in adults: Treatment and prevention", section on 'Prevention'.)

●Flu vaccination – Influenza vaccination is recommended for children with asthma, children ages two through four years with recurrent wheezing, and adults with asthma. Vaccination with inactivated influenza virus does not increase the risk of an asthma exacerbation, and yearly vaccination is encouraged in order to reduce the risks of complications of influenza infection (ie, pneumonia) [22,23]. Live-attenuated influenza vaccine is not licensed for children or adults with asthma or children with a history of wheezing. (See "Seasonal influenza in children: Prevention with vaccines" and "Seasonal influenza vaccination in adults".)

●Pneumococcal vaccination – Pneumonia complicates approximately up to 5 percent of pediatric asthma exacerbations [24], and the rate of invasive pneumococcal disease is greater among individuals with asthma [25]. Guidelines advise administering the 23-valent pneumococcal polysaccharide vaccine (PPSV23) to adults with asthma (table 3). (See "Pneumococcal vaccination in adults".)

Indications for vaccination of children with the 13-valent pneumococcal conjugate vaccine (PCV13) or 20-valent pneumococcal conjugate vaccine (PCV20) and PPSV23 are discussed separately. (See "Pneumococcal vaccination in children".)

ALLERGENS

Inhalant allergens — Allergy is a primary cause of asthma symptoms [1,2]. Thus, the clinician must take a thorough history to determine if the patient has significant allergies. A questionnaire has been published to assist the clinician in assessing the relationship between allergen exposure and the presence of symptoms (table 1).

Common inhalant allergens that can contribute to poor asthma control and cause exacerbations include [26-29]:

●Animal allergens (both pets and pests: cats, dogs, rodents)

●House dust mites (present in all but arid or high-altitude regions)

●Cockroaches

●Indoor and outdoor fungi (mold, mildew) [30] (see "Building-related illness and building-related symptoms", section on 'Mold')

●Outdoor pollen allergens (tree, grass, ragweed pollen)

If the patient suspects an allergic trigger, it is often helpful for them to keep a diary (recording exposures, activity/environment, ingestions, and peak expiratory flow readings) to see if there is a correlation between symptoms, lung function, and the suspected trigger.

Allergy testing (ie, skin testing or in vitro immunoglobulin E [IgE] immunoassays) can help confirm or exclude suspected triggers and should be performed in patients with persistent asthma, especially those who are exposed to perennial allergens [31]. It is important that the results are interpreted in the context of other diagnostic assessments, including medical history and physical examination, because a positive skin test or in vitro test (IgE immunoassay) result only means that the patient is sensitized to that allergen and has the potential to develop symptoms when exposed to that allergen. The diagnosis of allergy requires that the patient also has a history consistent with symptoms following exposure. (See "Overview of skin testing for IgE-mediated allergic disease" and "Overview of in vitro allergy tests".)

Measures for reducing exposure to indoor and outdoor allergens and guidelines for allergen immunotherapy are detailed separately. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis" and "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy" and "Sublingual immunotherapy for allergic rhinitis and conjunctivitis: SLIT-tablets".)

Food allergens — Patients with food allergy may exhibit asthma symptoms as part of food-induced anaphylaxis, but food allergens rarely cause isolated asthma without other symptoms. Anaphylaxis should be suspected if a patient (especially a child or young adult) develops severe asthma symptoms soon after eating a food allergen in the absence of other apparent triggers. Patients with food allergy should avoid the culprit food and carry injectable epinephrine. (See "Clinical manifestations of food allergy: An overview" and "Management of food allergy: Avoidance".)

Rarely, food allergens can be aerosolized in sufficient amounts that highly sensitized patients can develop asthmatic symptoms. As examples, patients sensitive to seafood, hen's egg, or cow's milk may react to steam, vapors, or sprays from the cooking or processing of these foods. A number of wheat flour-associated allergens can cause asthma symptoms via inhaled flour (baker's asthma). Asthmatic reactions to inhaled food allergens are reviewed separately. (See "Management of food allergy: Avoidance", section on 'Skin contact and inhalation' and "Respiratory manifestations of food allergy" and "Grain allergy: Clinical features, diagnosis, and management".)

Sulfite sensitivity, although not an IgE-mediated food allergy, can present with isolated asthma symptoms triggered by the ingestion of foods that are treated with sulfites to prevent spoilage and discoloration. The foods include wine, vinegar, dried fruits, processed potato products, and others (table 4). Up to 10 percent of adults with asthma may exhibit adverse reactions to the sulfites, which may include life-threatening reactions [32]. (See "Allergic and asthmatic reactions to food additives", section on 'Sulfites and related compounds'.)

Ingestion of alcoholic beverages may lead to asthma exacerbations in patients with aspirin-exacerbated respiratory disease (AERD) or systemic mastocytosis. (See "Aspirin-exacerbated respiratory disease", section on 'Reactions to alcoholic beverages'.)

Occupational allergens — Patients may develop asthma for the first time as a result of exposure to allergens in the workplace. This is referred to as occupational asthma and has been attributed to certain low-molecular-weight chemicals and high-molecular-weight organic materials (table 5). Common culprits in occupational asthma include toluene diisocyanates, trimellitic anhydrides, enzymes, and wood dusts. Occupational asthma is distinct from "work-aggravated asthma," or preexisting asthma that worsens in the workplace setting. These disorders are reviewed in greater detail separately. (See "Occupational asthma: Definitions, epidemiology, causes, and risk factors".)

IRRITANTS (INCLUDING CIGARETTE SMOKE) — A variety of irritants can induce asthma symptoms, including cigarette smoke, cannabis smoke, fireplace smoke, ashes, aerosol sprays, perfumes, cooking odors, musty odors, shower steam, traffic fumes, air pollution, desert dust, and workplace irritants [33-39].

Cigarette smoke — Cigarette smoke is a common airway irritant. Among patients with asthma, smokers have more severe symptoms, increased emergency department visits, increased rates of hospitalization, accelerated decline in lung function, and impaired responses to inhaled and systemic glucocorticoids than nonsmokers [40-42]. Children with environmental tobacco smoke exposure have a higher risk of developing asthma, more severe asthma symptoms, and more frequent exacerbations [43-45]. Smoking cessation is associated with improved lung function [46]. In addition, exposure to tobacco smoke exacerbates inflammatory airway responses to allergens [47].

Clinicians should advise patients with asthma to avoid personal and secondhand smoking [1]. Pediatricians should discuss smoking habits with parents and caregivers of pediatric patients. If a parent or caregiver is unwilling or unable to quit smoking, discuss not smoking in the same room in which children sleep or play. If feasible, instruct parents and caregivers to restrict their smoking to outside of the home. (See "Overview of smoking cessation management in adults".)

Cannabis smoke — Cannabis (also called marijuana) smoke contains end products of pyrolysis similar to tobacco smoke, including polycyclic aromatic hydrocarbons and reactive oxygen species, and appears to alter airway immune function [48]. While cannabis has bronchodilator effects, which could be seen as beneficial in asthma, cannabis-induced bronchodilation can have the disadvantage of enabling greater penetration of smoke to smaller airways than cigarette smoke [49]. (See "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)

The specific clinical effects of cannabis smoking in patients with asthma have not been fully studied, but frequent cannabis smoking (≥52 times/year) among young adults, after controlling for tobacco use, is associated with increased morning cough (odds ratio [OR] 3.46, 95% CI 2.02-5.93), sputum (OR 3.45, 95% CI 1.96-6.11), and wheeze (OR 1.95, 95% CI 1.11-3.42) [50]. In this study, quitting cannabis smoking was associated with a reduction in these symptoms to the level of nonusers. Based on these observations, patients with asthma should avoid exposure to cannabis smoke [49].

While the majority of respiratory effects of cannabis smoking are attributed to the irritant effects of the smoke, rare patients develop specific IgE-mediated allergy to Can s3, a lipid transfer protein. Sensitivity to Can s3 is associated with allergy symptoms to banana, tomato, and citrus but not via bet v1 sensitivity [49]. It may be that patients with IgE-mediated allergy to these food products should avoid all exposures (inhaled, oral) to cannabis. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)".)

Indoor air pollution — Fumes from unvented gas stoves have been associated with wheezing in children [51]. Changing to a nonpolluting, more effective indoor heat system is associated with an improved sense of well-being and reduced asthma symptoms in children, although not an improvement in lung function [33]. Wood burning stoves and fireplaces can also increase asthma symptoms.

Indoor exposures to volatile organic compounds (VOCs) and fragrances are thought to contribute to asthma, although supportive data are limited [52-54]. VOCs (eg, benzene, toluenes, xylenes, formaldehyde) are found in cleaning fluids, newly installed carpeting, paint, and furnishings in homes and offices [34,55]. Choosing unscented and nonaerosol products without VOC off-gassing and increasing air exchanges can minimize exposure to VOCs [56]. Chlorine bleach, while not a VOC, is an airway irritant.

Outdoor air pollution — Increases in ambient particulate matter (PM), elemental carbon/soot, nitrogen dioxide, and ozone have been associated with an increase in reports of wheeze, sales of short-acting bronchodilator medication, and hospitalizations for asthma [57-59]. Conversely, decreases in ambient air pollutants (nitrogen dioxide, ozone, and PM) in Southern California over 30 years of monitoring have been associated with decreases in chronic cough, chest congestion, and phlegm in children [36]. For a median reduction in nitrogen dioxide of 4.9 parts per billion (ppb), the OR for bronchitic symptoms among children with asthma at age 10 years was 0.79 (95% CI 0.67-0.94), with an absolute decrease in prevalence of 10 percent. For PM <2.5 microns (PM_2.5), the OR for a decrease in bronchitic symptoms was 0.68 (95% CI 0.53-0.86) for a median reduction in PM_2.5 of 6.8 mcg/m³, and the absolute decrease in prevalence was 15.4 percent.

Wildfire smoke — Wildfires result in short- to medium-term exposure to high levels of particulate matter and elemental carbon/soot, which may exacerbate asthma symptoms. Climate change and land-use change are worsening the risk of wildfires, with anticipated increases in number and extent of extreme fires in coming decades [60]. In one report analyzing the impact of the 2023 Canadian wildfire smoke on residents of New York City, the number of emergency department visits for asthma symptoms during the three-day period of peak smoke exposure was 44 percent higher (261 versus 182 per day; incidence rate ratio 1.44, 95% CI 1.3-1.6) than during unexposed reference periods [61]. This period of smoke exposure coincided with an over 10-fold increase in PM_2.5 levels (101 versus 9 mcg/m³) in the New York City area. A much longer burning, severe fire similarly worsened air quality in Eastern Australia for 19 weeks in 2019 to 2020, with 55 days of high PM_2.5 (mean exposure 32 mcg/m³) during this period [62]. Survey data of patients with severe asthma indicate that over 80 percent suffered worsening symptoms over this timeframe [63], with particularly worsened symptoms in those with predisposition to cough and throat irritation (laryngeal hypersensitivity) [64]. Additional information on the larger health impacts of wildfire smoke and management of wildfire health risks are discussed separately. (See "Climate emergencies", section on 'Wildfires'.)

Desert dust and coastal red tide — Days with high concentrations of desert dust are associated with an increase in asthma hospitalizations [35]. Desert dust contains quartz particles (crystalline silica), which have been associated with respiratory disease in occupationally exposed persons. Dust particles originating from desert dust storms in one location can be transported across the atmosphere to affect wide regions of the globe.

Red tide blooms due to the marine dinoflagellate, Karenia brevis, occur along the Gulf of Mexico and are associated with aerosolization of brevetoxin produced by the organism [65,66]. Observational studies suggest that inhalational exposure can lead to increases in asthma symptoms and decreases in lung function [65,67].

Workplace irritants — Workplace irritants, such as glacial acetic acid, cleaning products, and chlorine, are commonly used by factory workers and professional cleaners. (See "Irritant-induced asthma".)

ATMOSPHERIC CONDITIONS

Temperature and humidity — Extremes of temperature and humidity can cause bronchoconstriction and increase asthma symptoms during physical activity. Other weather conditions, such as thunderstorms, cause asthma exacerbations in some patients.

●Temperature and humidity can influence the severity of exercise-induced asthma [68]. While the precise mechanism is not clear, the inhalation of cold and dry air appears to increase bronchoconstriction during or shortly after exercise. One theory suggests that increased breathing during exercise causes water loss in the airways. This water loss leads to an exchange of molecules in the cells lining the airways, causing inflammation that ultimately leads to bronchoconstriction [69].

A second theory suggests increased breathing during exercise leads to cooling of the airways. This cooling is followed by the rapid flow of blood into airway blood vessels and resultant edema [69,70]. (See "Exercise-induced bronchoconstriction".)

●Hot, humid air can sometimes cause bronchoconstriction, as demonstrated in animal studies and a small study of humans [71]. The response to hot, humid air is blunted by pretreatment with inhaled ipratropium, suggesting that the bronchoconstriction is mediated by vagal bronchopulmonary C-fiber sensory nerves.

●Conditions related to climate change are predicted to increase exposure to asthma triggers. They may include more hot, sunny days that increase ozone-related asthma symptoms, rises in sea level or altered rainfall that may affect the dampness of indoor environments leading to more dust mite and mold growth, and higher ambient carbon dioxide levels that may increase exposure to allergens by lengthening the pollen season [72,73].

Thunderstorms — Asthma exacerbations that occur in the hours following a thunderstorm are known as "thunderstorm asthma." Epidemics of thunderstorm asthma generally occur during pollen seasons and occur worldwide, with nearly half reported in Australia [74-76]. In the 30 hours after a thunderstorm in Melbourne in 2016, 3400 excess visits to emergency departments for respiratory symptoms were reported across the city [77]. Studies of weather events have found increased levels of allergens present in the air, particularly pollen and mold spores, and most patients with thunderstorm asthma have pollen-induced seasonal allergic rhinitis [78,79]. Wet conditions at the beginning of a thunderstorm can cause pollen grains to rupture, increasing the concentration of pollen debris [80]. This debris can be inhaled into the lower airways, triggering an asthma exacerbation [81]. Elevated ozone levels may also play a role [82], but this has not been replicated [76]. In a multicenter study of adults from Melbourne with a past diagnosis of thunderstorm asthma and/or seasonal allergic rhinitis, risk factors for thunderstorm asthma were reported to include higher rye grass specific IgE levels, eosinophil counts, and fractional exhaled nitric oxide levels, and, if associated with presentation to a hospital, lower lung function and higher scores on the Asthma Control Questionnaire [79].

Potential interventions

●Simply being aware of these triggers can help patients prepare for different environments and anticipate problems to gain a better sense of control over their asthma.

●Masks and scarves that trap heat and moisture when a person breathes out and warm cold air during inhalation may help persons with asthma who work, exercise, or spend time in cold temperatures [83].

●Use of a short-acting beta-agonist (SABA; such as albuterol) prior to exercise in cold or dry conditions or at the onset of storms during pollen seasons can help prevent symptom flares.

●Patients whose asthma is triggered by pollen or mold allergy should be made aware that the conditions at the beginning of a thunderstorm during pollen season can be particularly troublesome and advised to avoid being outdoors during thunderstorms.

PHYSICAL ACTIVITY — Exercise-induced bronchoconstriction (EIB) affects 80 to 90 percent of people with symptomatic asthma. However, aerobic exercise has substantial health benefits and may lessen sensitivity to asthma triggers [84-86]. Thus, exercise should be encouraged, not avoided. The evaluation and management of EIB are discussed separately. (See "Exercise-induced bronchoconstriction".)

Certain interventions can help reduce asthma symptoms during exercise and can be tailored to the clinical setting (table 6):

●Ensure that asthma is well controlled. Exercise-related symptoms are more likely to occur when asthma is poorly controlled. (See "An overview of asthma management".)

●Anticipate problems related to temperature and humidity of inspired air (eg, cold, dry air, or high humidity).

●Build-up the patient's activity level gradually as better cardiovascular fitness reduces the minute ventilation required for a given level of exercise.

●The role of a preexercise warm-up is unclear and should be based on the individual patient's experience.

●Keep a short-acting beta-agonist (SABA; such as albuterol) on hand to treat asthma symptoms. Some people may use a SABA 5 to 15 minutes prior to exercise to prevent symptoms.

●Additional pharmacologic options for the management of exercise-triggered asthma are discussed separately. (See "Exercise-induced bronchoconstriction", section on 'Management' and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Use in exercise-induced asthma' and "Antileukotriene agents in the management of asthma".)

HORMONAL FLUCTUATIONS — Hormonal fluctuations associated with the menstrual cycle and with pregnancy can affect the frequency and severity of asthma symptoms in some patients.

Perimenstrual asthma — Worsening of asthma symptoms prior to or during menstruation, known as perimenstrual asthma, has been reported in up to 30 percent of females with asthma [87,88], although other studies have not been able to clearly replicate this syndrome [89]. The pathophysiology responsible for this phenomenon is unclear, although changes in estradiol, progesterone, and testosterone levels have been associated with changes in markers of atopy and asthma (eg, fractional exhaled nitric oxide and skin test diameters), upregulation of eosinophils and mast cells, and increased bronchial reactivity [88,90-92]. Females with hormonally associated asthma tend to have more severe disease than females whose asthma is unaffected by hormone levels, and near-fatal events have been reported in association with perimenstrual asthma patients [93].

As females may take nonsteroidal antiinflammatory drugs (NSAIDs) to control premenstrual syndrome and dysmenorrhea, it is important to determine that a perimenstrual flare in asthma symptoms is not caused by ingestion of an NSAID by a patient with aspirin-exacerbated asthma. Aspirin sensitivity may be more prevalent in females with perimenstrual asthma [87]. (See "Aspirin-exacerbated respiratory disease".)

The optimal pharmacologic management of perimenstrual flares of asthma has not been determined [90]. Asthma medications may need perimenstrual adjustment to prevent asthma flares.

Leukotriene-receptor antagonists appeared protective against perimenstrual worsening of asthma in one small series [94].

Pregnancy — Pregnancy can aggravate asthma in approximately one-third of patients, while one-third experience no change, and one-third experience symptomatic improvement. Thus, asthma should be monitored closely during pregnancy. (See "Asthma in pregnancy: Clinical course and physiologic changes" and "Management of asthma during pregnancy".)

MEDICATIONS — Certain medications can aggravate asthma, including:

●Beta blockers – Nonselective beta blockers can cause airflow limitation and reduce the bronchodilating effect of inhaled beta agonists and are generally avoided in patients with asthma. Selective beta-1 blockers cause a decrease in forced expiratory volume in one second (FEV₁) of 7 percent on average but ≥20 percent in some patients. The effects of beta-blocking agents are reviewed separately. (See "Treatment of hypertension in asthma and COPD".)

In addition, topical beta blocker eye drops, especially nonselective ones (eg, timolol) [95] but also cardioselective ones (eg, betaxolol) [96], have been reported to reduce lung function and induce asthma hospitalizations, presumably through its systemic absorption [97].

●Aspirin and NSAIDs – Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can cause acute severe exacerbation of asthma in patients with aspirin-exacerbated respiratory disease (AERD). Patients with AERD should avoid aspirin and all NSAIDs that inhibit cyclooxygenase 1, unless they have been desensitized to aspirin (table 7). Caution is advised when prescribing aspirin or other NSAIDs to patients with asthma and nasal polyposis. (See "Aspirin-exacerbated respiratory disease".)

●ACE inhibitors – Angiotensin-converting enzyme (ACE) inhibitors can cause cough, which could be mistaken for increased asthma symptoms, and rarely have been associated with worsening asthma control. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Cough' and "Treatment of hypertension in asthma and COPD", section on 'ACE inhibitors'.)

For many years, it was believed that excessive drying of bronchial secretions by first-generation antihistamines (due to their anticholinergic properties) would adversely affect asthma. However, this effect was never demonstrated to be clinically significant. Newer, nonsedating antihistamines have less of an anticholinergic effect and appear beneficial in the treatment of asthma [98].

Careful review of the medication list is appropriate for asthma patients presenting with increased asthma symptoms.

EMOTIONAL FACTORS — Anxiety, depression, chronic stress, and stressors, such as exposure to community violence, are associated with greater rates of asthma exacerbations in patients with asthma [99-101]. Parental/caregiver depression and perceived stress are associated with wheeze and more severe asthma in children [102,103].

Counseling (eg, cognitive behavioral therapy) and sometimes medications can help alleviate depression and anxiety [101,104]. Some patients may need help distinguishing between asthma flares and panic attacks. Psychologists and family counselors can assist patients and parents/caregivers of children with asthma with stress management and provide advice if asthma disrupts a patient's or family's personal life. (See "Generalized anxiety disorder in adults: Cognitive-behavioral therapy and other psychotherapies" and "Management of panic disorder with or without agoraphobia in adults" and "Psychotherapy for anxiety disorders in children and adolescents".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Avoiding asthma triggers (The Basics)" and "Patient education: Asthma in children (The Basics)" and "Patient education: Asthma in adults (The Basics)" and "Patient education: Secondhand smoke and children (The Basics)" and "Patient education: Exercise-induced asthma (The Basics)")

●Beyond the Basics topics (see "Patient education: Trigger avoidance in asthma (Beyond the Basics)" and "Patient education: How to use a peak flow meter (Beyond the Basics)" and "Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)" and "Patient education: Exercise-induced asthma (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Common triggers for asthma – Common triggers for asthma exacerbations include respiratory tract infections, airborne allergens (for patients with allergic asthma), inhaled irritants (eg, tobacco smoke), extremes of temperature and humidity (eg, very cold, dry air), and physical exercise (table 1). (See 'Respiratory infections' above and 'Allergens' above and 'Irritants (including cigarette smoke)' above and 'Atmospheric conditions' above and 'Physical activity' above.)

•Food allergens rarely cause isolated asthma without other symptoms. However, patients with food allergy may exhibit asthma symptoms as part of food-induced anaphylaxis, and inhaled food allergens can occasionally provoke asthma symptoms. (See 'Food allergens' above.)

•A variety of irritants can induce asthma symptoms, including cigarette and cannabis smoke, fireplace smoke, ashes, aerosol sprays, perfumes, cooking odors, musty odors, shower steam, traffic fumes, air pollution, desert dust, and workplace irritants (eg, glacial acetic acid, cleaning products, chlorine). (See 'Irritants (including cigarette smoke)' above.)

•Extremes of temperature and humidity can cause bronchoconstriction and increase asthma symptoms during physical activity. Other weather conditions, such as thunderstorms, cause asthma exacerbations in some patients. (See 'Atmospheric conditions' above.)

●Exercise should be encouraged – While exercise-induced bronchoconstriction (EIB) affects 80 to 90 percent of people with symptomatic asthma, aerobic exercise has substantial health benefits and may lessen sensitivity to asthma triggers. Thus, exercise should be encouraged, not avoided. Certain interventions can reduce asthma symptoms during exercise (table 6). (See 'Physical activity' above.)

●Relationship to menstruation – Worsening of asthma symptoms prior to or during menstruation, known as perimenstrual asthma, has been reported in up to 30 percent of females with asthma. Pregnancy can aggravate asthma in approximately one-third of females, while one-third experience no change, and one-third experience symptomatic improvement. (See 'Hormonal fluctuations' above.)

●Medications – Medications, such as beta blockers (particularly nonselective beta blockers), aspirin and nonsteroidal antiinflammatory drugs (NSAIDs), and angiotensin-converting enzyme (ACE) inhibitors can cause asthma flares in some individuals, although ACE inhibitors more typically cause a cough without asthma. (See 'Medications' above.)

●Mental health and external stressors – Anxiety, depression, and chronic stress, such as exposure to community violence, are associated with greater rates of asthma exacerbations in patients with asthma. Parental/caregiver depression and stress are associated with more severe asthma in children. Interventions, such as cognitive behavioral therapy, counselling about stress management, and sometimes medication, can help ameliorate these triggers. (See 'Emotional factors' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William Bailey, MD, who contributed to earlier versions of this topic review.