Asthma is a disease that causes narrowing of the airway in the lung for which there is obstruction of the airflow into the lung and from the lung. There is also mucus production. So people with asthma have difficulty in breathing, coughing, etc.
What is Asthma?
Asthma, a heterogeneous disease, occurs due to obstruction of airflow in the tube that carries air into the lung and from the lung. This airflow obstruction may vary from person to person spontaneously or even after taking treatment. Those who have asthma have a special type of inflammation in their airways in the lung.
This inflammation makes them more sensitive to a wide range of triggers. This causes excessive narrowing of the airway in the lung. Due to the narrowing of the tube (airway), less amount of air can pass through it and causes wheezing ( whistling sound) and dyspnea ( difficulty breathing).
Narrowing of the airway usually comes back to normal, but in few cases, with chronic asthma, there may be an element that causes narrowing of the tube ( airway) that does not return to normal. So this narrowed tube persists in the lung and causes associated symptoms such as difficulty in breathing etc.
Asthma symptoms can be controlled, but these symptoms can not be cured.
Asthma Risk factors and Triggers:
Genetic and environmental factors have a major role in the development of asthma. Several risk factors are present within our body. These risk factors are- Genetic role, allergy (atopy), Airway hyper responsiveness, gender, obesity, and early viral infections.
Environmental factors
Environmental factors include Indoor allergens, outdoor allergens, occupational sensitizers, passive smoking, respiratory infections, air pollution ( diesel particulates, nitrogen oxides), diet, dampness and mold exposure, acetaminophen ( paracetamol), etc.
Allergens, upper respiratory tract viral infections, exercise and hyperventilation, cold air, sulfur dioxide, and irritant gases, drugs (beta-blockers, aspirin), Stress, Irritants (household sprays, paint fumes)
Allergy (atopy)
Allergy (atopy) is a major risk factor for asthma. Patients with asthma commonly suffer from other allergic (atopic) diseases such as allergic rhinitis or atopic dermatitis (eczema).
The allergens that make a person more prone to asthma are house dust mites, cat and dog fur, cockroaches, grass and tree pollens, and rodents ( specifically for laboratory workers).
Allergy is caused by the genetically determined production of specific IgE antibodies, so many patients have a family history of allergic diseases.
Genetic role
The familial association of asthma and the development of asthma in identical twins indicate that there are some genetic factors associated with the development of asthma.
Study shows that different genes play a role for the development of asthma. Moreover, the severity of asthma is also genetically determined. So genes play a role to determine if your asthma will be mild, moderate, or severe. Interesting right! The study also shows that the interaction between genetic factor and environmental factor will ultimately determine that who will be more prone to get asthma.
Infections
It is seen that exacerbation of asthma occurs after viral infections, mostly after rhinovirus infection. It is not confirmed to date if viral infection solely causes the occurrence of asthma or other factors also have some effect on it.
It is found that there is some association between respiratory syncytial virus infection in infants and the development of asthma in them. Mycoplasma and Chlamydophila bacterial infections are also associated with the development of severe asthma.
Living in a damp house with exposure to mold spores is a potential risk factor for asthma. So removal of these factors improves asthma.
Diet
It is a controversial factor for the development of asthma. Research shows that diets with a low amount of antioxidants such as vitamin C, vitamin A, magnesium, selenium, and omega-3 polyunsaturated fat ( fish oil) are associated with asthma.
Also, a diet with a high amount of sodium and omega-6 polyunsaturated fatty acid causes an increased risk of asthma. Vitamin D deficiency also makes you more prone to get asthma.
Obesity particularly in women is a risk factor and many obese people are suffering from asthma. So maintaining a proper diet stuffed with essential nutrients is very important. Not only that but maintaining proper body weight is also important to get rid of asthma symptoms. Sounds surprising right?…
Air pollution
We all know air pollution increases the chances to get asthma. Many times we see that people with asthma complaining that their symptoms getting worse due to air pollution.
Indeed, air pollutants such as sulfur dioxide, ozone, and diesel particulates may trigger your asthma symptoms. Exposure to road traffic pollutants such as nitrogen dioxide and diesel particulates is associated with increased asthma symptoms. Nitrogen oxide exposure from cooking stoves and exposure to passive cigarette smoke may also lead to asthma.
Allergens
Exposure to house dust mites in early childhood is a risk factor for allergic sensitization and asthma. So be aware!
Occupational exposure
Occupational asthma is common. In fact, it may affect up to 10 percent of young adults. Chemicals such as toluene diisocyanate and trimellitic anhydride can cause asthma.
Small animal allergens in laboratory workers or fungal amylase in wheat flour in bakers may also lead to asthma. Cleaners commonly develop occupational asthma due to the exposure to aerosols of cleaning liquids.
How do you know if you have occupational asthma? Simple, you can suspect occupational asthma if your symptoms improve during holidays or on weekends.
Obesity
It is seen that asthma occurs more commonly in obese people ( BMI greater than 30 kg per meter square). If you are obese, then it is more difficult to control asthma.
Though other factors are also related to the development of asthma, the pro-inflammatory adipokines released from fat cells with reduced release of anti-inflammatory cytokines from fat cells are linked with the development of asthma in obese people. Sounds difficult!
Let me make it simple. Obesity creates an environment within the body that is more favorable to get asthma. So weight management is very important. It’s pretty simple right!
Other factors
Other factors are also responsible for the development of asthma. These factors are
- Lower maternal age
- Duration of breastfeeding
- Prematurity and low birth weight
- Inactivity
- Acetaminophen ( paracetamol) consumption in childhood may be linked to increased oxidative stress and ultimately make the child more prone to get asthma.
Nonallergic asthma (intrinsic asthma)
About 10 percent of asthma patients have negative skin tests to common inhalant allergens and normal serum concentration of IgE. So these people are not allergic.
These people with non-allergic or intrinsic asthma, usually show asthma later in their life (adult-onset asthma). They commonly have nasal polyps and maybe aspirin sensitivity. These people usually have more severe, persistent asthma.
What is the cause of asthma in these nonallergic patients?
There are many causes that lead to asthma in these non-allergic patients such as
- Increased local production of IgE in the airways may be a cause.
- Also staphylococcal enterotoxins act as super antigens may be a cause.
- Type 2 innate lymphoid cells may cause eosinophilic inflammation in these non-allergic patients and can cause asthma.
Asthma Triggers
Several stimuli cause narrowing of the airway, wheezing, and dyspnea in people with asthma. So avoiding these triggers are effective in controlling asthma. The common asthma triggers are the following. Let’s have a look
Allergens
Most common allergens that trigger asthma are Dermatophagoides species. Environmental exposure may lead to chronic symptoms that are throughout the year. Another round of the year allergens come from cats, other domestic pets, cockroaches.
Not only that, there are seasonal allergens that also cause asthma. The seasonal allergens are grass pollen, ragweed, tree pollen, fungal spores. Pollens usually cause allergic rhinitis rather than asthma, but due to thunderstorms, pollen grains are disrupted to and fro and the particles that are released can trigger severe asthma exacerbation ( thunderstorm asthma).
Virus infections
Upper respiratory tract virus infections such as rhinovirus, respiratory syncytial virus, coronavirus are the most common triggers for acute severe exacerbations of asthma. How do these viruses make you get asthma? Let me explain.
The virus causes increase airway inflammation with increased numbers of eosinophils and neutrophils. There may be reduced production of type 1 interferons by epithelial cells of asthma patients, this leads to increased susceptibility to these viral infections and ultimately a greater inflammation. Greater inflammation leads to greater asthma!
Drugs
Many drugs may trigger asthma. Beta-blockers acutely worsen asthma. Angiotensin converting enzyme inhibitors and aspirin may also worsen asthma.
Exercise
Especially in children exercise commonly triggers asthma. Exercise induced asthma typically begins after the end of exercise and recovers spontaneously within 30 minutes. Exercise induced asthma gets worsens during cold and dry climates than hot and humid conditions. So exercise induced asthma is more commonly seen in sports such as cross country running in cold weather, overland skiing, ice hockey than in swimming.
Exercise induced asthma may be prevented by prior administration of drugs such as beta2 agonist and antileukotrienes. But the best way to prevent it is by regular treatment with an inhalational corticosteroid.
Physical factor
Cold air, hyperventilation may trigger asthma. Laughter may also trigger asthma. In many people, asthma worsens in hot weather and during weather changes. Asthma may get worsen due to exposure to strong smells or perfumes.
Food and diet
Symptoms of asthma are triggered by particular foods. Shellfish and nuts may cause severe allergic reactions associated with wheezing. It is seen that patients with aspirin ( acetylsalicylic acid) induced asthma get to benefit from a salicylate free diet.
Certain food additives may trigger asthma. Food preservative such as metabisulfite may trigger asthma because it releases sulfur dioxide gas in the stomach. Yellow food coloring agents Tartrazine may also trigger asthma.
Air pollution
Increased exposure to sulfur dioxide, ozone, diesel particulates, and nitrogen oxides cause increased symptoms of asthma.
Occupational factors
Many substances we are exposed to in the workplace can trigger asthma because they act as sensitizing agents. In the case of occupational asthma, it is characteristically associated with symptoms at work and relief from asthma symptoms on weekends and holidays.
Interesting to note that if you can remove your exposure to these substances within the first 6 months of symptoms, then there is usually complete recovery from asthma. But more persistent symptoms lead to permanent airway changes. So the early detection of this type of asthma and early avoidance of these substances are very important.
Hormones
Some women have worsening asthma before their menstrual period. Sometimes this asthma is very severe. A fall in the level of progesterone may be related to it. So in severe cases patient may get relief by using a high dose of progesterone or gonadotropin releasing factors. Thyrotoxicosis and hypothyroidism may also worsen asthma.
Stress
Stress may cause worsening your asthma symptoms. Psychological factors can cause narrowing of the airway that leads to asthma. But surprisingly it is found that very severe stress such as bereavement usually does not worsen asthma, it actually may improve asthma symptoms!
Cells and Mediators that Cause Asthma:
There are various cells and mediators that cause asthma. These are
- Inflammatory cells- Mast cells, Eosinophils, T helper 2 cells, Basophils, Neutrophils, and Platelets.
- Structural cells- Epithelial cells, Smooth muscle cells, Endothelial cells, Fibroblast s and nerves.
- Mediators: Histamine, Leukotrienes, Prostanoids, PAF, Kinins, Adenosine, Endothelins, Nitric oxide, Cytokines, Chemokines, Growth factors.
Asthma Types:
Depending on the severity Asthma is classified into 4 categories (types)
- Mild intermittent: when mild asthma symptoms persist up to 2 days a week and up to 2 nights a month
- Mild persistent: when asthma symptoms appear more than twice a week, but no more than once in a single day
- Moderate persistent: when asthma symptoms appear once a day and more than one night a week
- Severe persistent: Here asthma symptoms persist throughout the day on most days and frequently at night.
Asthma Symptoms:
The characteristic symptoms of asthma are
- Wheezing
- Dyspnea, breathlessness
- Chest tightness or chest pain
- Coughing
- Trouble sleeping due to shortness of breath, coughing, or wheezing
Symptoms of asthma get worse at night and patients with asthma typically awake in the early morning hours. There is difficulty in filling the lungs with air. There is increased mucus production, this mucus is typically tenacious, so it is difficult to expectorate.
The ventilation is increased and the patient may use accessory muscles of ventilation. Before the asthma attack, there may have few symptoms such as itching under the chin, discomfort in the upper back ( between the scapulae) or there may be inexplicable fear( impending doom)
Signs of Asthma:
Typical physical signs are inspiratory, and to a greater extent expiratory. Rhonchi throughout the chest, hyperinflation. Some people, especially children may have a dry (non-productive) cough. If asthma is under control, then there may have no abnormal physical findings.
Signs of Asthma Worsening:
Signs that your asthma may be worsening are
- Asthma signs and symptoms become more frequent than before
- Breathing difficulty is increasing with time
- The need to use a rapid relief inhaler and you are using it more frequently than before
Asthma- when to seek for doctor?
Severe acute asthma attacks are life-threatening, so if you have the following symptoms then seek emergency medical care
- Rapid worsening of shortness of breath or wheezing or severe breathing difficulty
- Using a quick-relief inhaler gives no improvement
Asthma Diagnosis:
The diagnosis of asthma is usually prominent from the symptoms of variable and intermittent airway obstruction. But asthma must be confirmed from different tests.
Lung function tests
Spirometry confirms airflow limitation in your lung with the reduction in FEV1, reduction in FEV1/FVC ratio, and PEF. Greater than 12 percent reversibility is demonstrated and 200 ml increase in FEV1 15 minutes after an inhaled short acting beta2 agonist ( example- inhaled albuterol 400 micrograms) or in some patients by a 2-4 weeks trial of oral corticosteroids ( prednisone or prednisolone 30-40 mg daily).
Measurements of PEF two times daily can confirm the diurnal ( in the morning and evening) variations in airflow obstruction. Flow volume loops show reduced peak flow and reduced maximum expiratory flow.
No further lung function test is normally needed, but whole body plethysmography shows increased airway resistance to airflow. It may also show increased total lung capacity and residual volume. Gas diffusion, measured by carbon monoxide transfer, is usually normal, but in some patients, it may be increased slightly.
Airway responsiveness
If your airway has increased hyperresponsiveness then it is normally measured by methacholine or histamine challenge test. There is a calculation of the provocation concentration that reduces FEV1 by 20 percent.
This test is not normally needed, but can be done in the differential diagnosis of chronic cough and if the diagnosis is in doubt because of normal pulmonary function tests. If a patient gives a history of exercise induced asthma then exercise testing is done to see the post exercise airway obstruction ( bronchoconstrictions).
Allergen challenge test is normally not needed but can be done if there is a history of occupational asthma. It will help to identify occupational agents that act as an allergen and causes asthma.
Hematologic tests
In the case of asthma, blood tests normally are not helpful. But total serum IgE and specific IgE to inhaled allergens may be measured.
Imaging
Chest X-ray is usually normal. Severe patients may show hyperinflated lungs or bronchial wall thickening. In case of exacerbations, there may be evidence of a pneumothorax.
Lung shadowing indicates normally pneumonia or eosinophilic infiltrates in patients with bronchopulmonary aspergillosis. High resolution CT may also be done, but usually not needed.
Chest CT may help to identify bronchiolitis, bronchiectasis, tracheobronchomalacia, endobronchial lesions, and vascular abnormalities.
Skin tests
Skin prick test may be done on common inhalant allergens ( house dust mite, cat fur, grass pollen). This test is positive for allergic asthma. It is negative in non allergic (intrinsic) asthma.
But this test is not helpful in the diagnosis of asthma. Still, if the test gives a positive skin response then it may be useful to identify the allergen and avoid those allergens as a preventive measure.
Exhaled NO
Fractional exhaled nitric oxide is a non-invasive test. Non-invasive test means that test tools will not physically enter inside your body or there will be no break in your skin.
This test measures eosinophilic airway inflammation. Here typically elevated levels in asthma are reduced by inhalational corticosteroids. So this test helps to find the response of asthma to treatment.
Asthma Differential Diagnosis:
Few diseases are commonly mistaken as asthma. These diseases are
- Upper airway obstruction by a tumor or laryngeal edema. These conditions may mimic severe asthma.
- Endobronchial obstruction with a foreign body can cause persistent wheezing in a specific area of the chest and may mimic asthma.
- Left ventricular failure may mimic the wheezing of asthma.
- Vocal cord dysfunction may mimic asthma.
- Eosinophilic pneumonia and systemic vasculitis including Churg- Strauss syndrome and polyarteritis nodosa may show wheezing, so may mimic asthma.
In the diagnosis of asthma, it is very important to rule out the above mentioned diseases.
Asthma Treatment:
Asthma treatment goal
There are many effective and safe therapies to manage asthma. The main aim of asthma therapy are
- Minimal ( ideally no) chronic symptoms, including nocturnal symptoms.
- Minimal ( infrequent) exacerbations
- No emergency visits
- Minimal ( ideally no) use of a required beta2 agonist
- No limitations of activities, including exercise
- Peak expiratory flow circadian variations less than 20 percent
- (Near ) normal peak expiratory flow
- Minimal or no adverse effects from medicine
Mode of treatment in asthma
Two modes of treatments are given to asthma patients
- Drug therapy
- Non drug therapy or non pharmacologic approach
Drug therapy in asthma (medicines)
Main drugs of asthma –
- Bronchodilators that give rapid relief from asthma symptoms mainly by relaxation of airway smooth muscles.
- Asthma controllers inhibit the underlying inflammation.
Bronchodilator therapy
The main purpose of bronchodilator therapy is to reverse the obstructions (bronchoconstrictions) of airway smooth muscle in asthma. So it helps to give rapid relief from symptoms.
But bronchodilator therapy has nothing to do with the underlying inflammation because bronchodilators have little or no effect on underlying inflammation. So this therapy is insufficient to control asthma in patients with persistent symptoms.
Three types of bronchodilators are commonly used – beta2 adrenergic agonists ( most effective), anticholinergics, and theophylline.
Beta2 agonists
Beta2 agonists help to relax smooth muscle cells in the airway and also inhibit inflammatory cells, mainly mast cells. It inhibits mast cell mediator release, also inhibits sensory nerve activation. So it is very effective in asthma treatment.
Beta 2 agonists are usually taken by inhalation. Short acting beta 2 agonists (for example- albuterol and terbutaline) have a duration of action of 3-6 hours. They act rapidly and can give you symptom relief. When there is an increased use of short acting beta2 agonists then it indicates asthma is uncontrolled.
High dose short acting beta2 agonist are taken by nebulizer or via a metered-dose inhaler (MDI) with a spacer.
Long acting beta2 agonists ( salmeterol and formoterol) have a duration of action over 12 hours. Normally it is taken by inhalation two times daily.
Long acting beta2 agonist should be taken with inhalational corticosteroid therapy because long acting beta2 agonist can not control underlying inflammation. So fixed combination inhalers of a corticosteroid and long acting beta2 agonist are highly effective to control asthma and also to prevent exacerbations.
Side effects are minimal when beta2 agonists are taken by inhalation. In elderly people, muscle tremors and palpitations can occur as a side effect.
Anticholinergics
Anticholinergic ipratropium bromide inhibit cholinergic nerve induced airway obstruction (bronchoconstrictions) and mucus secretion. It is less effective than beta2 agonist in asthma therapy.
Long acting tiotropium bromide or glycopyrronium bromide may be used additionally in patients with asthma where asthma is not controlled despite using maximal doses of inhalational corticosteroid- long acting beta agonist combinations.
In this case, it improves lung function and decreases exacerbations. A high dose of short acting anticholinergic can be given by nebulizer to treat acute severe asthma but should be given only after beta2 agonist.
Side effects of anticholinergics are minimal. The most common side effect is dry mouth. For those who faces dry mouth, we recommend to try dry mouth home remedies, it will help. In elderly, urinary retention and glaucoma may occur.
Theophylline
Nowadays, theophylline is not commonly used in asthma treatment due to its side effects. Aminophylline is occasionally used via slow IV infusion in person with severe exacerbations of asthma that does not respond to the short acting beta agonist.
Asthma controller therapy
Inhaled corticosteroids
It is the most effective therapy to control asthma. These inhaled corticosteroids are the most effective anti inflammatory, they decrease inflammatory cell numbers and their activation in the airway, so decrease the inflammation in the airway. As a result, asthma symptoms are improved.
It is the most effective controller for the management of asthma. They can be used in asthma of any severity and age. It is normally given two times daily, but for mild symptomatic asthma, one time daily is effective enough. Inhaled corticosteroids rapidly improve the symptoms of asthma, but lung function improves over several days.
It is also effective to prevent asthma symptoms such as exercise induced asthma and nocturnal ( at night) exacerbations. It can prevent severe exacerbations. The use of inhaled corticosteroids also reduces airway hyperresponsiveness to allergens. But to get the maximum improvement several months of therapy may be needed.
Withdrawal of inhaled corticosteroids leads to slow deterioration of asthma control, so it is clear that it does not cure the underlying condition, it just suppresses the airway inflammation and associated symptoms.
Inhaled corticosteroids have local side effects such as hoarseness of voice and oral candidiasis. These local side effects can be decreased by using a large volume spacer device.
Systemic corticosteroids
Systematic corticosteroids (for example- hydrocortisone or methylprednisolone ) are given through an intravenous route in case of acute severe asthma.
Oral corticosteroids ( usually prednisone or prednisolone 30-40 mg once daily for 5-10 days) are used to treat acute exacerbations of asthma. Approx.1 percent of asthma patients need maintenance treatment with oral corticosteroids, but it is given in the lowest possible dose that can control the symptoms.
Abdominal obesity, bruising, osteoporosis, diabetes, hypertension, gastric ulceration, proximal myopathy, depression, and cataracts may occur as side effects.
If side effects occur, then steroid therapy should be stopped and treatment with other drugs should be followed. If a patient requires maintenance with oral corticosteroid therapy then bone density monitoring is very important.
Antileukotrienes
Antileukotrienes such as montelukast and zafirlukast are also used in the treatment of asthma. But they are less effective than inhalational corticosteroids.
If the patient is not controlled with low doses of inhalational corticosteroids then antileukotrienes can be used additionally. It is also less effective than long acting beta2 agonist.
Antileukotrienes are to be taken orally once or twice daily. They are well tolerated.
Cromones
Cromolyn sodium and nedocromil sodium are effective to control trigger induced asthma such as exercise induced asthma, allergen induced asthma, and sulfur dioxide induced asthma.
Cromolyn is not effective for the long term control of asthma. They are very safe to use.
Previously cromolyn was used in the treatment of childhood asthma, but now low doses of inhalational corticosteroids are preferred.
Steroid sparing therapies
Methotrexate, Cyclosporin A, Azathioprine, Gold, IV gamma globulin are used as steroid sparing therapies in patients who show serious side effects with steroid therapy. But this steroid sparing therapy provides no long term benefit because it is also associated with a high risk of side effects.
Anti IgE
Omalizumab inhibits IgE mediated reactions, so it helps to decrease the number of exacerbations in severe asthma patients and also improves asthma conditions. Omalizumab is given as a subcutaneous injection every 2-4 weeks. But this treatment is very expensive, so not normally recommended.
Non drug therapy in asthma (alternative therapies)
Alternative therapies include hypnosis, breathing control, acupuncture, yoga, etc. may be a treatment of choice for some patients. This alternative therapy can be continued side by side with drug therapy.
Complications of Asthma:
There are several complications of asthma such as
- Asthma may interfere with your work, sleep, or other activities
- Permanent narrowing of the tube that carries air from the lung and to the lung. So breathing can be affected
- Long term use of asthma medicines have side effects that may give you associated complications
Proper and timely treatment of asthma will reduce the complications due to asthma. Also, early treatment gives better long term outcomes.
Prevention of Asthma:
There is no way to prevent asthma, but a proper step by step plan can help you to prevent future asthma attacks.
Identify asthma triggers and avoid them
There are several asthma triggers such as allergens and irritants that trigger asthma attacks. Find out those triggers and avoid them.
Monitor your breathing
If you feel you are developing the symptoms of asthma such as shortness of breath, coughing, etc. then do not delay getting the medical care. Early treatment always gives a better outcome.
You may also use a home peak flow meter to measure and record your peak airflow regularly. Your doctor will show you how to monitor your peak flow at home. If you find any change in peak flow, contact your doctor early.
Take the prescribed medicine as directed
Always follow the instructions of your doctor. Do not stop taking the asthma medications without asking your doctor. If your condition improves then also do not discontinue medicines without your doctor’s advice.
Always carry the medication with you when you visit your doctor. Take the right dose of medicine and follow the doctor’s instructions.
Pay attention to the number of quick relief inhalers use
If you are using more frequently quick relief inhaler than before then your asthma is not under the control or your asthma is worsening. Always contact your doctor in this case. Do not take a quick relief inhaler blindly without consulting your doctor.
Takeaway:
Asthma is a disease that can be controlled if proper prevention is taken. Early detection and early treatment always give good results.
Asthma can not be cured, but it can be controlled. There are many causes of asthma. Depending upon the cause and depending upon the severity ( mild, moderate, or severe) asthma treatment may vary.
Do not take asthma medicine blindly. Always consult with your doctor before taking any asthma medicine. Follow up with your doctor is very important in the treatment of asthma. Follow your doctor’s instructions and maintain all the preventive measures. Stay healthy and happy.
