Asthma; Types, Causes, Symptoms, Diagnosis, Treatment

Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These episodes may occur a few times a day or a few times per week. Depending on the person, they may become worse at night or with exercise.

Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation [Rx]. The interaction of these features of asthma determines the clinical manifestations and severity of asthma [Rx] and the response to treatment.

Asthma is a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyperresponsiveness and an underlying inflammation. This interaction can be highly variable among patients and within patients over time. This section presents a definition of asthma, a description of the processes on which that definition is based—the pathophysiology and pathogenesis of asthma, and the natural history of asthma.

Epidemiology

According to a report from the Centers for Disease Control and Prevention (CDC), 1 in 13 people has asthma. It affects 25.7 million Americans, including 7.0 million children younger than 18 years. It is a significant health and economic burden on patients, families, and society. Important epidemiologic issues include:

• In 2010, 1.8 million people visited an emergency room for asthma-related care, and 439,000 people were hospitalized because of asthma.
• The most recent data obtained from the CDC shows prevalence in males at about 6.5% and in females about 9.1%.
• Regarding race distribution, the prevalence is 7.8% in the white population, 10.3% in the black community and 6.6% in the Hispanic population.
• WHO estimates that 235 million people currently have asthma.
• The annual incidence of occupational asthma ranges from 12 to 170 cases per million worked. The prevalence is reported at 5% to 15% across many different industries.
• Asthma is the most common noncommunicable disease among children.
• Most deaths occur in older adults.

Types of Asthma

• Allergic (extrinsic) – Your doctor may refer to asthma as being “extrinsic” or “intrinsic.” A better understanding of the nature of asthma can help explain the differences between them. Extrinsic, or allergic asthma, is more common and typically develops in childhood. Approximately 70%-80% of children with asthma also have documented allergies. Typically, there is a family history of allergies. Additionally, other allergic conditions, such as nasal allergies or eczema, are often also present. Allergic asthma often goes into remission in early adulthood. However, in many cases, the asthma reappears later.
• Nonallergic (intrinsic) asthma – Intrinsic asthma represents a small amount of all cases. It usually develops after the age of 30 and is not typically associated with allergies. Women are more frequently affected and many cases seem to follow a respiratory tract infection. Obesity also appears to be a risk factor for this type of asthma. Intrinsic asthma can be difficult to treat and symptoms are often chronic and year-round.

Or

Depending on the type of trigger, doctors classify asthma as being either allergic or non-allergic.

• Allergic asthma – is also called “extrinsic asthma” because the trigger comes from outside the body and is breathed in with the air. Different people may have reactions to very different types of triggers, including cigarette smoke (active and passive smoking), plant pollen, animal fur, dust mite excrement, and some kinds of food as well as cold air, perfume, exhaust fumes and certain chemicals.
• Non-allergic asthma –  (also called “intrinsic asthma”) is caused by triggers that come from inside the body. These triggers include bacterial and viral inflammations of the airways in particular. Sometimes taking certain kinds of painkillers causes asthma. These painkillers include acetylsalicylic acid (ASA, the drug in medicines like Aspirin) and other non-steroidal anti-inflammatory drugs (NSAIDs). In some people, physical or emotional stress that makes them breathe faster can also trigger asthma symptoms.

According to the severity

• Mild intermittent – This includes attacks no more than twice a week and nighttime attacks no more than twice a month. Attacks last no more than a few hours to days. Severity of attacks varies, but there are no symptoms between attacks.
• Mild persistent – This includes attacks more than twice a week, but not every day, and nighttime symptoms more than twice a month. Attacks are sometimes severe enough to interrupt regular activities.
• Moderate persistent – This includes daily attacks and nighttime symptoms more than once a week. More severe attacks occur at least twice a week and may last for days. Attacks require daily use of quick-relief (rescue) medication and changes in daily activities.
• Severe persistent – This includes frequent severe attacks, continual daytime symptoms, and frequent nighttime symptoms. Symptoms require limits on daily activities.

Others Types of Asthma

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Asthma exacerbation

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An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness. The wheezing is most often when breathing out. While these are the primary symptoms of asthma, some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.In children, chest pain is often present.

Signs occurring during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest. A blue color of the skin and nails may occur from lack of oxygen.

In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min, or ≥50% of the predicted best. Moderate is defined as between 80 and 200 L/min, or 25% and 50% of the predicted best, while severe is defined as ≤ 80 L/min, or ≤25% of the predicted best.

• Acute severe asthma – previously known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and corticosteroids. Half of cases are due to infections with others caused by allergen, air pollution, or insufficient or inappropriate medication use.
• Brittle asthma – is a kind of asthma distinguishable by recurrent, severe attacks. Type 1 brittle asthma is a disease with wide peak flow variability, despite intense medication. Type 2 brittle asthma is background well-controlled asthma with sudden severe exacerbations.
• Exercise-induced – Exercise can trigger bronchoconstriction both in people with or without asthma.It occurs in most people with asthma and up to 20% of people without asthma. Exercise-induced bronchoconstriction is common in professional athletes. The highest rates are among cyclists (up to 45%), swimmers, and cross-country skiers. While it may occur with any weather conditions, it is more common when it is dry and cold.Inhaled beta2-agonists do not appear to improve athletic performance among those without asthma, however, oral doses may improve endurance and strength.
• Occupational – Asthma as a result of (or worsened by) workplace exposures is a commonly reported occupational disease. Many cases, however, are not reported or recognized as such. It is estimated that 5–25% of asthma cases in adults are work-related. A few hundred different agents have been implicated, with the most common being: isocyanates, grain and wood dust, colophony, soldering flux, latex, animals, and aldehydes. The employment associated with the highest risk of problems include: those who spray paint, bakers and those who process food, nurses, chemical workers, those who work with animals, welders, hairdressers and timber workers.
• Aspirin-induced asthma – Aspirin-exacerbated respiratory disease, also known as aspirin-induced asthma, affects up to 9% of asthmatics. Reactions may also occur to other NSAIDs. People affected often also have trouble with nasal polyps. In people who are affected, low doses paracetamol or COX-2 inhibitors are generally safe.
• Alcohol-induced asthma – Alcohol may worsen asthmatic symptoms in up to a third of people.This may be even more common in some ethnic groups such as the Japanese and those with aspirin-induced asthma. Other studies have found improvement in asthmatic symptoms from alcohol.
• Nonallergic asthma – Nonallergic asthma, also known as intrinsic or nonatopic asthma, makes up between 10 and 33% of cases. There is negative skin test to common inhalant allergens and normal serum concentrations of IgE. Often it starts later in life, and women are more commonly affected than men. Usual treatments may not work as well

Phenotypes

Owing to the heterogeneity of the disease, a number of different phenotypes can be described. Distinguishing between them can be particularly relevant to the therapy in severe cases:

• Allergic asthma
• Nonallergic asthma
• Pediatric asthma/recurrent obstructive bronchitis
• Late-onset asthma
• Asthma with fixed airflow obstruction
• Obesity asthma
• Occupational asthma
• Asthma in the elderly
• Severe asthma

Classifications by other professional associations (ERS/ATS, European Respiratory Society/American Thoracic Society) tend to focus more on a combination of clinical and pathophysiological aspects (e. g., eosinophilic/neutrophilic asthma, severe allergic asthma etc.)

Causes of Asthma

Asthma triggers are different from person to person and can include:

• Airborne substances, such as pollen, dust mites, mold spores, pet dander or particles of cockroach waste
• Respiratory infections, such as the common cold
• Physical activity (exercise-induced asthma)
• Cold air
• Air pollutants and irritants, such as smoke
• Certain medications, including beta blockers, aspirin, ibuprofen and naproxen 
• Strong emotions and stress
• Sulfites and preservatives added to some types of foods and beverages, including shrimp, dried fruit, processed potatoes, beer and wine
• Gastroesophageal reflux disease (GERD), a condition in which stomach acids back up into your throat
• Asthma is a chronic inflammatory disorder of the airways. This feature of asthma has implications for the diagnosis, management, and potential prevention of the disease.
• The immunohistopathologic features of asthma include inflammatory cell infiltration:
  • Neutrophils (especially in sudden-onset, fatal asthma exacerbations; occupational asthma, and patients who smoke)
  • Eosinophils
  • Lymphocytes
  • Mast cell activation
  • Epithelial cell injury

• Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and disease chronicity.
• In some patients, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis.
• Gene-by-environment interactions are important to the expression of asthma.
• Atopy, the genetic predisposition for the development of an immunoglobulin E (IgE)-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma.
• Viral respiratory infections are one of the most important causes of asthma exacerbation and may also contribute to the development of asthma.

Sign Symptoms of Asthma

Early warning signs of asthma include. Intermittent and variable (may also be absent, e.g., during symptom-free intervals or in mild disease)

• Shortness of breath (often in acute episodes)
• Expiratory wheezes
• Chest pressure sensation
• Cough
• Frequent cough, especially at night
• Losing your breath easily or shortness of breath
• Feeling very tired or weak when exercising
• Wheezing or coughing after exercise
• Feeling tired, easily upset, grouchy, or moody
• Decreases or changes in lung function as measured on a peak flow meter
• Signs of a cold or allergies (sneezing, runny nose, cough, nasal congestion, sore throat, and headache)
• Trouble sleeping

Common signs and symptoms of asthma include

• Coughing – Coughing from asthma often is worse at night or early in the morning, making it hard to sleep.
• Wheezing – Wheezing is a whistling or squeaky sound that occurs when you breathe.
• Chest tightness – This may feel like something is squeezing or sitting on your chest.
• Shortness of breath – Some people who have asthma say they can’t catch their breath or they feel out of breath. You may feel like you can’t get air out of your lungs.
• Increasing difficulty breathing – (measurable with a peak flow meter, a device used to check how well your lungs are working)
• Exercise-induced asthma – which may be worse when the air is cold and dry
• Occupational asthma – triggered by workplace irritants such as chemical fumes, gases or dust
• Allergy-induced asthma – triggered by airborne substances, such as pollen, mold spores, cockroach waste or particles of skin and dried saliva shed by pets (pet dander)
• Shortness of breath
• Trouble sleeping caused by shortness of breath, coughing or wheezing
• A whistling or wheezing sound when exhaling (wheezing is a common sign of asthma in children)
• Coughing or wheezing attacks that are worsened by a respiratory virus, such as a cold or the flu

Other symptoms of an asthma attack include

• Severe wheezing when breathing both in and out
• Coughing that won’t stop
• Very rapid breathing
• Chest pain or pressure
• Tightened neck and chest muscles, called retractions
• Difficulty talking
• Feelings of anxiety or panic
• Pale, sweaty face
• Blue lips or fingernails

Diagnosis of Asthma

You may also be given lung (pulmonary) function tests to determine how much air moves in and out as you breathe. These tests may include:

• Spirometry – This test estimates the narrowing of your bronchial tubes by checking how much air you can exhale after a deep breath and how fast you can breathe out.
• Peak flow – A peak flow meter is a simple device that measures how hard you can breathe out. Lower than usual peak flow readings are a sign your lungs may not be working as well and that your asthma may be getting worse. Your doctor will give you instructions on how to track and deal with low peak flow readings.

Additional tests of Asthma

Other tests to diagnose asthma include

• Methacholine challenge – Methacholine is a known asthma trigger that, when inhaled, will cause mild constriction of your airways. If you react to the methacholine, you likely have asthma. This test may be used even if your initial lung function test is normal.
• Imaging tests – A chest X-ray and high-resolution computerized tomography (CT) scan of your lungs and nose cavities (sinuses) can identify any structural abnormalities or diseases (such as infection) that can cause or aggravate breathing problems.
• Allergy testing – This can be performed by a skin test or blood test. Allergy tests can identify allergy to pets, dust, mold and pollen. If important allergy triggers are identified, this can lead to a recommendation for allergen immunotherapy.
• Sputum eosinophils – This test looks for certain white blood cells (eosinophils) in the mixture of saliva and mucus (sputum) you discharge during coughing. Eosinophils are present when symptoms develop and become visible when stained with a rose-colored dye (eosin).
• Provocative testing for exercise and cold-induced asthma – In these tests, your doctor measures your airway obstruction before and after you perform vigorous physical activity or take several breaths of cold air.

Treatment of Asthma

The goals of pharmacotherapy are the suppression of the inflammation of asthma and the reduction of bronchial hyperreactivity and airway obstruction. The medications used for these purposes belong to two groups:

• Relievers (medications taken for symptomatic relief as necessary) include mainly the inhaled, rapidly-acting beta2 sympathomimetic agents, e.g., the short-acting drugs salbutamol, fenoterol, and terbutaline and the long-acting drug formoterol. Inhaled anticholinergic drugs and rapidly-acting theophylline (solution or drops) play a secondary role as relievers.
• Controllers (medications used for preventive, maintenance therapy) include the inhaled corticosteroids (ICS), inhaled long-acting beta2 agonists (LABA) such as formoterol or salmeterol, montelukast, and delayed-release theophylline preparations.

Formoterol can be used as a reliever because of its rapid onset of action or as a controller in combination with corticosteroids.

Medications

Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation. Antibiotics are generally not needed for sudden worsening of symptoms.

Step-Up Therapy: The Goal of Asthma Control

• Step 1 – For intermittent asthma, preferred therapy is a short-acting inhaled beta2 agonist. For persistent asthma, daily medication is recommended.
• Step 2 – Preferred treatment is a low-dose inhaled corticosteroid.
• Step 3 – A low dose inhaled corticosteroid plus a long-acting inhaled beta2 agonist is recommended, or a medium-dose inhaled corticosteroid.
• Step 4 – The preferred treatment is a medium-dose inhaled corticosteroid plus a long-acting beta2 agonist.
• Step 5 – The preferred treatment is high dose inhaled corticosteroid plus a long-acting beta2 agonist and considering omalizumab for people with allergies.
• Step 6 –The preferred treatment is high-dose inhaled corticosteroid plus a long-acting beta2 agonist plus an oral corticosteroid; consider omalizumab with people with allergies.

For steps 2 to 4, also consider allergy immunotherapy and allergy testing. Leukotriene receptor antagonists, cromolyn sodium, and theophylline can be used as alternative treatments but not preferred agents. Leukotriene inhibitors have shown to improve exercise-induced asthma by 50% for children 12 and older.

Fast–acting

• Short-acting beta₂-adrenoceptor agonists (SABA), such as salbutamol (albuterol USAN) are the first line of treatment for asthma symptoms. They are recommended before exercise in those with exercise induced symptoms.
• Anticholinergic medications, such as ipratropium bromide, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms. Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA. If a child requires admission to hospital additional ipratropium does not appear to help over a SABA.
• Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs.They are however not recommended due to concerns regarding excessive cardiac stimulation.
• Combination of inhaled anticholinergic and beta2 agonist which have been shown to decrease hospitalization of school-aged children
• Intravenous magnesium sulfate has also been shown to increase lung function and decrease hospitalization in children
• Administering systemic corticosteroids within one hour of an emergency room or urgent care presentation has a significant effect on patients with severe exacerbation and also decreases hospitalization
• Patients should be sent home on oral prednisone after an acute hospitalization [rx]

Long–term control

• Corticosteroids – are generally considered the most effective treatment available for long-term control. Inhaled forms such as beclomethasone are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed. It is usually recommended that inhaled formulations be used once or twice daily, depending on the severity of symptoms.
• Long-acting beta-adrenoceptor agonists – (LABA) such as salmeterol and formoterol can improve asthma control, at least in adults, when given in combination with inhaled corticosteroids. In children this benefit is uncertain. When used without steroids they increase the risk of severe side-effects, and with corticosteroids, they may slightly increase the risk. Evidence suggests that for children who have persistent asthma, a treatment regime that includes LABA added to inhaled corticosteroids may improve lung function but does not reduce the amount of serious exacerbations. Children who require LABA as part of their asthma treatment may need to go to the hospital more frequently.
• Leukotriene receptor antagonists – (anti-leukotriene agents such as montelukast and zafirlukast) may be used in addition to inhaled corticosteroids, typically also in conjunction with a LABA. Evidence is insufficient to support use in acute exacerbations. For adults or adolescents who have persistent asthma that is not controlled very well, the addition of anti-leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations. Anti-leukotriene agents may be effective alone for adolescents and adults, however, there is no clear research suggesting which people with asthma would benefit from anti-leukotriene receptor alone. In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids by the British Thoracic Society in 2009. A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children. A similar class of drugs, 5-LOX inhibitors, may be used as an alternative in the chronic treatment of mild to moderate asthma among older children and adults. As of 2013 there is one medication in this family known as zileuton.
• aminophylline – Intravenous administration of the drug does not provide an improvement in bronchodilation when compared to standard inhaled beta-2 agonist treatment. Aminophylline treatment is associated with more adverse effects compared to inhaled beta-2 agonist treatment.
• Mast cell stabilizers – (such as cromolyn sodium) are another non-preferred alternative to corticosteroids.
• For children with asthma which is well-controlled on combination therapy of inhaled corticosteroids (ICS) and long-acting beta₂-agonists (LABA), the benefits and harms of stopping LABA and stepping down to ICS-only therapy are uncertain.
• In adults who have stable asthma while they are taking a combination of LABA and inhaled corticosteroids (ICS), stopping LABA may increase the risk of asthma exacerbations that require treatment with corticosteroids by mouth.
• Stopping LABA probably makes little or no important difference to asthma control or asthma-related quality of life. Whether or not stopping LABA increases the risk of serious adverse events or exacerbations requiring an emergency department visit or hospitalisation is uncertain.

Delivery methods

Medications are typically provided as metered-dose inhalers (MDIs) in combination with an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms. However, insufficient evidence is available to determine whether a difference exists in those with severe disease. There is no strong evidence for the use of intravenous LABA for adults or children who have acute asthma.

The most commonly used asthma medications include the following

• Short-acting bronchodilators (albuterol) – provide quick relief and can be used in conjunction for exercise-induced symptoms.
• Inhaled steroids fluticasone – mometasone ciclesonide, flunisolide are first-line anti-inflammatory therapy.
• Long-acting bronchodilators – (salmeterol formoterol vilanterol) can be added to ICS as additive therapy. LABAs should never be used alone for the treatment of asthma.
• Leukotriene – modifiers can also serve as anti-inflammatory agents.
• Anticholinergic agents – (ipratropium , tiotropium [Spiriva], umeclidinium [Incruse Ellipta]) can help decrease sputum production.
• Anti-IgE – treatment can be used in allergic asthma.
• Anti-IL5 treatment – (mepolizumab , reslizumab ) can be used in eosinophilic asthma.
• Chromones stabilize mast cells – (allergic cells) but are rarely used in clinical practice.
• Theophylline – also helps with bronchodilation (opening the airways) but is rarely used in clinical practice due to an unfavorable side-effect profile.
• Systemic steroids – (prednisone, prednisolone , methylprednisolone, dexamethasone ) are potent anti-inflammatory agents that are routinely used to treat asthma exacerbations but pose numerous unwanted side effects if used repeatedly or chronically.
• Numerous additional monoclonal antibodies – are also currently being studied and will likely be available within the next couple of years.
• Immunotherapy – or allergy shots have been shown to decrease medication reliance in allergic asthma.
• There are no home remedies that have proven benefit for asthma.

• Acupuncture
• “Alexander technique” training of breathing
• Air moisture control
• Breathing exercises
• Buteyko breathing technique
• Chiropractic manipulation
• Dietary measures: fish oil, fatty acids, mineral supplementation or restriction, vitamin C
• Homeopathy
• Hypnosis
• Ionizers (room-air purifiers)
• Plant extracts (phytotherapeutic agents)
• Relaxation therapy, including progressive relaxation as described by Jacobson, hypnotherapy, autogenic training, biofeedback training, transcendental meditation
• Speleotherapy (living in underground caves and mines)
• Traditional Chinese medicine (rx), (rx).

Others

When asthma is unresponsive to usual medications, other options are available for both emergency management and prevention of flareups. For emergency management other options include:

• Oxygen to alleviate hypoxia if saturations fall below 92%.
• Corticosteroid by mouth are recommended with five days of prednisone being the same 2 days of dexamethasone. One review recommended a seven-day course of steroids.
• Magnesium sulfate intravenous treatment increases bronchodilation when used in addition to other treatment in moderate severe acute asthma attacks. In adults it results in a reduction of hospital admissions.
• Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.
• Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.
• Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists. Their use in acute exacerbations is controversial.
• The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest; however, there is no evidence from clinical trials to support this.
• For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs, bronchial thermoplasty may be an option. It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies. While it may increase exacerbation frequency in the first few months it appears to decrease the subsequent rate. Effects beyond one year are unknown.
• Evidence suggests that sublingual immunotherapy in those with both allergic rhinitis and asthma improve outcomes.
• Omalizumab may also be useful in those with poorly controlled allergic asthma.
• It is unclear if non-invasive positive pressure ventilation in children is of use as it has not been sufficiently studied.

Alternative medicine

Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use. Air ionisers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.

Manual therapies, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic maneuvers, have insufficient evidence to support their use in treating asthma. The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medication use; however, the technique does not have any effect on lung function. Thus an expert panel felt that evidence was insufficient to support its use.

• Inhaled short-acting beta2 sympathomimetic agents – Fine tremor of voluntary muscle; agitation; tachycardia; palpitations
• Inhaled long-acting beta2 sympathomimetic agents (LABA) – Same adverse effects as short-acting agents; also: tolerance of bronchoprotective effect in the presence of bronchoconstricting stimuli (while the bronchodilating effect of the drug is maintained); to be used over the long term only in combination with glucocorticoids (usually ICS)
• Inhaled corticosteroids (ICS) – oropharyngeal candidiasis (thrush); hoarsenessSystemic: depending on the dose and the duration of administration, osteoporosis; cataracts; glaucoma; delayed growth in childhood; suppression of adrenocortical function
• Systemic corticosteroids – Cushing syndrome; osteoporosis; myopathy; glaucoma; cataracts; endocrine psychosyndrome; worsening of diabetes mellitus; sodium retention; hypertension; adrenocortical atrophy; elevated susceptibility to infection
• Montelukast – Abdominal symptoms; a headache; unclear association with Churg-Strauss syndrome, thus the dose of simultaneously administered systemic glucocorticoids should be lowered cautiously
• Theophyllin – Depending on the serum concentration: gastrointestinal disturbances; gastroesophageal reflux disorder; tachycardia; diuresis; agitation; insomnia When the serum concentration exceeds 25 mg/L: epileptic seizures; gastrointestinal bleeding; ventricular arrhythmia; hypotension
• Omalizumab – Local reactions at the subcutaneous injection site; a headache

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References

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• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696883/
• https://www.ncbi.nlm.nih.gov/books/NBK526018/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923754/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768124/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768124/
• https://www.ncbi.nlm.nih.gov/books/NBK279520/
• https://www.ncbi.nlm.nih.gov/books/NBK7223/
• https://www.ncbi.nlm.nih.gov/books/NBK430901/

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