Asthma – Types, Triggers & Treatment

Asthma is a common chronic disorder of the airways that involves a complex interaction of the following viz:

1. Airway inflammation. 
2. Intermittent airflow obstruction. 
3. Bronchial hyperresponsiveness.

This interaction can vary among patients and within the same patient over time. The airway inflammation contributes to airway hyperresponsiveness with an increase in mucus-secreting cells and the expansion of mucus-secreting glands with resultant increased mucus secretion causing thick mucus plugs that block the airway.

Also, Injury to the epithelium may cause epithelial peeling, which may further result in extreme airway impairment or airflow limitation, respiratory symptoms, and disease chronicity.

Also, the Loss of the epithelium’s barrier function allows allergens to penetrate, causing the airways to become further hyperresponsive. The degree of which depends largely on the extent of the inflammation and the individual’s immunologic response.

What is Asthma?

Asthma also known as bronchial asthma, is a long-term or chronic disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible airway constriction.

Types of Asthma

1. Childhood Asthma

This is the most common chronic condition in children. It can develop at any age, but it is slightly more common in aged 5–14 years children than in adults.

2. Adult-onset Asthma

This can develop at any age, including during adulthood.

3. Occupational Asthma

Occurs as a result of exposure to an allergen or irritant present in the workplace. About 1 out of 6 adult-onset cases, start at work. Both indoor and outdoor work environments can expose an individual to asthma triggers.

4. Seasonal Asthma

It occurs in response to allergens that are only in the surrounding environment at certain times of the year. For instance, cold air in the winter or pollen in the spring or summer may trigger symptoms of seasonal asthma. However, it does not always stem from an allergy.

5. Exercise-Induced Asthma

This type is triggered by exercise and is also called exercise-induced bronchospasms.

6. Asthma-COPD Overlap Syndrome (ACOS)

This type typically happens when you have both asthma and chronic obstructive pulmonary disease (COPD). Both diseases make it difficult to breathe.

7. Acute Severe Asthma

Some individuals have severe symptoms or severe refractory asthma for reasons that do not relate directly to asthma viz:

• From incorrect way to use an inhaler.
• Asthma does not respond to treatment, even with high dosages of medication or the correct use of inhalers
• Eosinophilic Asthma. (Eosinophils are a type of blood cell involved in an allergic reaction).

It may not respond to standard asthma management although, some may respond others will respond to biological medication that reduces the number of eosinophils, which can trigger asthma.

8. Reactive Airways Dysfunction Syndrome (RADS) and Irritant-Induced Asthma

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

• Develops in people with no history of asthma.
• Occurs following single, specific inhalation exposure to a significant amount of an irritating gas or particulate
• Persists for ≥ 3 months

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

While irritant-induced asthma refers to a similar persistent asthma-like response following multiple or chronic inhalational exposures to high levels of similar irritants.

Manifestations are sometimes more insidious, and thus the connection to inhalational exposure is clear only in retrospect.

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

Asthma Triggers

Common triggers include

• Environmental and occupational allergens (numerous).
• Exercise

Exercise can be a trigger, especially in cold or dry environments.

• Emotion

Emotions such as anxiety, anger, and excitement sometimes trigger exacerbations.

• Cold, Dry Air

Cold air alone can also trigger symptoms.

• Infections

Infectious triggers in young children include a respiratory syncytial virus, rhinovirus, and Para influenza virus infection. In older children and adults, upper respiratory infections (particularly with rhinovirus) and pneumonia are common infectious triggers.

• Inhaled Irritants

Inhaled irritants, such as air pollution, cigarette smoke, perfumes, and cleaning products can also trigger symptoms in patients with asthma. (Inhaled irritants that trigger asthma exacerbations do so by inducing a T2 response, in contrast to what happens in reactive airway dysfunction syndrome and chronic irritant-induced asthma.)

• Aspirin and Other NonSteroidal Anti-Inflammatory Drugs (NSAIDs)

Aspirin is a trigger in up to 30% of patients with severe asthma and more than 10% of all patients. Aspirin-sensitive asthma is typically accompanied by nasal polyps and nasal/sinus congestion, which is a condition also known as Samter’s triad (asthma, nasal polyps, and sensitivity to aspirin/Non-steroidal anti-inflammatory drugs (NSAIDs).

• GastroEsophageal Reflux Disease  (GERD)

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

Symptoms of Asthma

Patients with mild asthma are typically asymptomatic between exacerbations. Patients with more severe diseases and those with exacerbations experience:

• Difficulty in breathing (Dyspnea)
• Chest tightness. 
• Audible wheezing. (The shrill whistle or coarse rattle you hear when your airway is partially blocked)
• Coughing. 

Coughing may be the only symptom in some patients (cough-variant asthma). Symptoms can follow a circadian rhythm and worsen during sleep, or in the early hours of the morning. Many patients with more severe diseases awaken during the night (nocturnal asthma).

Signs include: 

• Wheezing.
• A fall of systolic blood pressure [BP] of more than 10 mm Hg during inspiration (Pulsus paradoxus). 
• Fast breathing (Tachypnea.) 
• Fast Heartbeats (Tachycardia)
• Visible efforts to breathe (use of neck and suprasternal [accessory] muscles.
• Upright posture, pursed lips, speech limited by dyspnea). 
• When severe, the expiratory phase of respiration is prolonged, with an inspiratory: expiratory ratio of at least 1:3. 
• Patients with a severe exacerbation and impending respiratory failure typically have some combination of altered consciousness, and cyanosis (a bluish discolouration of the skin due to poor circulation or inadequate oxygenation of the blood.
• Pulsus paradoxus of more than 15 mm Hg, oxygen saturation less than 90%, and PaCO2 more than 45 mm Hg. Chest x-ray reveals hyperinflation.

Symptoms and signs disappear between exacerbations, although soft wheezes may be audible during forced expiration at rest, or after exercise, in some asymptomatic patients. Hyperinflation of the lungs may alter the chest wall in patients with long-standing uncontrolled asthma, causing a barrel-shaped thorax.

Diagnosing Asthma

1. Clinical Evaluation

Diagnosis is based on history and physical examination and is confirmed with pulmonary function tests. Asthma and chronic obstructive pulmonary disease (COPD) are sometimes easily confused. They cause similar symptoms and produce similar results on pulmonary function tests but differ in important biologic ways that are not always clinically apparent

These biological mechanisms are not exclusive to either disease and can overlap between them. Asthma-COPD overlap (ACO) is being increasingly recognized as a unique entity that presents with persistent airflow obstruction and several features of both asthma and COPD.

2. Pulmonary Function Testing

Suspected patients should undergo pulmonary function testing to:

• Confirm and quantify the severity. 
• Reversibility of airway obstruction. 

Pulmonary function data quality is effort-dependent and requires patient education before the test. If it is safe to do so, bronchodilators should be stopped before the test: 

• 8 hours for short-acting beta-2 agonists, such as albuterol.
• 24 hours for ipratropium.
• 12 to 48 hours for theophylline.
• 48 hours for long-acting beta-2 agonists, such as salmeterol and formoterol.
• 1 week for tiotropium.

1. Spirometry

This test measures the amount of air the lungs can hold. The test also measures how forcefully one can empty air from the lungs. This should be done before and after the inhalation of a short-acting bronchodilator. 

Signs of airflow limitation before bronchodilator inhalation include:

• Reduced FEV1 (forced expiratory volume in 1 second (FEV1) is the maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation.
• A reduced FEV1/FVC ratio. 

This calculated ratio represents the proportion of a person’s vital capacity that can expire in the first second of forced expiration to the full, forced vital capacity.

• The FVC may also be decreased because of gas trapping, such that lung volume measurements may show an increase in the residual volume, the functional residual capacity, or both. 
• An improvement in FEV1 of more than  12% or an increase of more than 10% of predicted FEV1 in response to bronchodilator treatment confirms reversible airway obstruction, although the absence of this finding should not preclude a therapeutic trial of long-acting bronchodilators.

2. Provocative Testing

This and similar tests involve using triggers or challenges. Adults are more likely to have this test than children especially when symptoms and Spirometry tests don’t clearly show asthma or for patients suspected of having cough-variant asthma.

During this test, a chemical called methacholine is inhaled  (or alternatives, such as inhaled histamine or exercise testing) is used to provoke bronchoconstriction before and after Spirometry to see if it makes the airways narrow. 

If your results fall at least 20%, you may have asthma. Your doctor will give you medicine at the end of the test to reverse the effects of the methacholine.

This test is done provided there are no contraindications. Contraindications include.

• FEV1 1 L or < 50% predicted. 
• Recent myocardial infarction or stroke.
• Severe hypertension (systolic BP > 200 mm Hg; diastolic BP > 100 mm Hg). 

A decline in FEV1 of more than 20% on a provocative testing protocol is relatively specific for the diagnosis of asthma. However, FEV1 may decline in response to drugs used in provocative testing in other disorders, such as COPD. If FEV1 decreases by < 20% by the end of the testing protocol, asthma is less likely to be present.

3. Other tests

Other tests may be helpful in some circumstances:

• Diffusing Capacity for Carbon Monoxide (DLCO)

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

• Chest X-ray

A chest x-ray may help exclude some causes of asthma or alternative diagnoses, such as heart failure or pneumonia. The chest x-ray in asthma is usually normal but may show hyperinflation or segmental atelectasis, a sign of mucous plugging.

• Allergy Testing

Allergy testing may be indicated for children whose history suggests allergic triggers because these children may benefit from immunotherapy. 

It should also be considered for adults whose history indicates relief of symptoms with allergen avoidance and for those for whom a trial of therapeutic anti –IgE antibody therapy is being considered. 

• Blood Tests

Elevated blood eosinophil count  (> 400 cells/mcL [> 0.4 × 10⁹ /L]) and elevated nonspecific IgE levels are suggestive but are neither sensitive nor specific for a diagnosis of allergic asthma.

 It has been noted that eosinophil levels may vary during the mornings and afternoons. Generally, blood eosinophil levels are higher in the morning, and there may be falsely low eosinophil counts when samples are collected in the afternoon.

• Exhaled Nitric Oxide (FeNO)

This may be used in the evaluation when the diagnosis of asthma is unclear, especially in children more than 5 years of age. It can also be used as a biomarker to monitor disease severity and therapeutic efficacy.

One breathes into a tube connected to a machine that measures the amount of nitric oxide in the breath. The body makes this gas normally, but levels could be high if your airways are inflamed.

FeNO levels > 50 ppb are consistent with allergic airway inflammation, supporting an asthma diagnosis. A level < 25 ppb is more consistent with an alternative diagnosis. Levels between 25 and 50 ppb are indeterminate.

• Peak Expiratory Flow (PEF)

This device measures how fast one can blow air out of the lungs. Used for home monitoring of disease severity and for guiding therapy.

Prevention of Asthma

• Identify your asthma triggers.
• Stay away from Allergens
• Avoid smoking (1^st, 2nd and 3^rd hand smoking)
• Avoid cold environments.
• Allergy-proof your environment
• Vaccinate against flu.
• Take asthma medications as prescribed 
• Follow your asthma action plan.-take your meds, and keep an inhaler on you when there is an attack follow instructions given to you.

Treatment of Asthma

Asthma treatment aims to ease your symptoms. They might include:

1. Inhaled Corticosteroids 

These medications are used for long-term Asthma management. That means they are taken every day to keep asthma under control. They prevent and ease swelling inside your airways, and they may help your body make less mucus. A device called an inhaler is used to get the medicine into your lungs. They include:

• • Beclomethasone (QVAR)
  • Budesonide (Pulmicort)
  • Fluticasone

2. Leukotriene Modifiers

They block leukotrienes(things in the body that trigger an asthma attack). Common leukotriene modifiers include:

• Montelukast (singulair)
• Zafirlukast (Accolate)

3. Long-acting Beta-agonists

These medications relax the muscle bands that surround your airways. They are also called bronchodilators. They can be taken with an inhaler, even when you have no symptoms. They include:

• Formoterol
• Salmeterol

4. Combination Inhaler

This device gives you an inhaled corticosteroid and a long-acting beta-agonist together to ease your asthma. Common ones include:

• Fluticasone and salmeterol
• Budesonide and formoterol

5. Theophylline

This opens the airways and eases tightness in the chest. Can be taken by mouth, either by itself or with an inhaled corticosteroid.

6. Short-acting Beta-agonists

These are known as rescue medicines or rescue inhalers. They loosen the bands of muscle around your airways and ease symptoms. Examples include:

• Albuterol
• ventolin

7. Anticholinergic

These bronchodilators prevent the muscle bands around your airways from tightening. Common ones include:

• Ipratropium
• Tiotropium

You can get ipratropium in an inhaler or as a solution for a nebulizer, a device that turns liquid medicine into a mist that you breathe in through a mouthpiece. Tiotropium bromide comes in a dry inhaler, which lets you breathe in the medicine as a dry powder.

8. Oral and Intravenous Corticosteroids

They can be taken with a rescue inhaler during an asthmatic attack.  They ease swelling and inflammation in your airways. You’ll take oral steroids for a short time, between 5-14 days. They can be taken intravenously. Common oral steroids include:

• Methylprednisolone.
• Prednisolone.
• Prednisone.

9. Biologics

This is used for severe asthma unresponsive to treatment. They include:

• Omalizumab -treats asthma caused by allergens. Comes as an injection given every 2 to 4 weeks.

Other biologics stop your immune cells from making things that cause inflammation. These drugs include:

• Benralizumab
• Mepolizumab
• Reslizumab

10. Tezepelumab-ekko (Tezspire)

Is a first-in-class medicine indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older? Taken by injection, it targets a specific molecule that causes inflammation in the airways.

Conclusion

Asthma is a chronic condition and can be sometimes life-threatening so learn how to keep your asthma under control and prevent attacks. This you do by knowing your triggers and staying away from them. Also, follow your GP’s instructions on taking your medications. Keep track of your condition and learn the signs that it might be getting worse and finally know what to do if you think your asthma is getting worse.