Treatment of bronchial asthma – A simplified overview

ABSTRACT

The treatment of bronchial asthma is complex and includes both pharmacological and non-pharmacological approaches. The main goals of therapy are to achieve and maintain disease control, minimize symptoms, prevent exacerbations, and improve the patient’s quality of life. Inhaled corticosteroids (ICSs), bronchodilators, and biological therapy play a key role in severe forms of asthma. Patient education, identification and elimination of triggers of asthma attacks, and regular monitoring of the condition are also an integral part of disease management. Research in asthma management points to new therapeutic options that are tailored precisely to the endotype of the disease and the phenotype of the patient. Early diagnosis and individually tailored treatment are key factors to achieve remission and improve the prognosis of patients with bronchial asthma.

INTRODUCTION

Asthma is an incurable disease, but with medical treatment, patients can achieve a full and high quality of life comparable to healthy individuals. Asthma control is divided into two domains: symptom control and risk of adverse outcomes. Neglected symptom control often leads to worsening health and the return of recurrent exacerbations. In the short term, symptom control can be provided through the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), use of short-acting inhaled β2 agonist bronchodilator (SABA) releasers for complications, and avoidance of contact with triggers. One aspect of treatment is to take into account the severity of asthma.[1,2] Severe asthma remains uncontrolled despite optimal treatment, but it must be distinguished from intractable asthma. Moderate asthma is well controlled with a low or medium dose of inhaled corticosteroids (ICSs) (plus SABA as needed). Mild asthma is well controlled with low-intensity treatment.[3,4]

The management of bronchial asthma can be divided into pharmacological and non-pharmacological. According to Šperková (2018),[5] prevention of symptoms of already diagnosed asthma is possible by avoiding contact with the allergen or other trigger.

Non-pharmacological strategies in asthma management include certain interventions (e.g., physical activity, attending rehabilitation programmes, avoiding allergens, medication, food, tobacco or irritants, healthy eating, eliminating emotional stress or anxiety …) [Table 1].[6,7]

Table 1.

Asthma management non-pharmacological interventions

Intervention	Recommendation	Benefits
Physical activity	Encouraging asthma patients to incorporate regular physical activity into their lives Mediation of advice needed to prevent exercise-induced bronchoconstriction (warm-up, SABA or ICS-formoterol before exercise)	Improvement of cardiopulmonary fitness, lung function, reduction of symptoms, improvement of quality of life
Rehabilitation programmes	Encouraging asthma patients to participate in rehabilitation programmes for respiratory diseases A useful way to supplement asthma pharmacotherapy is breathing exercises	improvement of functional exercise capacity and quality of life Improving breathing control, strengthening breathing muscles, and reducing stress levels
Avoidance of allergens or irritants	Encouraging patients to remove as many allergens and irritants as possible from the home environment and its surroundings, especially patients with occupational asthma Avoidance of household allergens has been shown to be beneficial, particularly in children, but there is limited evidence of a beneficial effect in the adult population; this strategy can be complicated and financially challenging	Reduced risk of symptoms and exacerbations
Avoidance of medications that may make asthma worse	Necessary to notify the doctor of an allergy to certain types of medication Consider each patient individually according to history and tests performed	Through properly prescribed treatment, the overuse of drug combinations that might not ultimately have a beneficial effect on health is avoided
Avoidance tobacco exposure or smoking	Encourage people with asthma to quit smoking or vaping, to avoid environmental smoke exposure, and encourage parents to stop smoking (vaping) in close proximity to children	Improved expectoration of mucus General health benefits
Healthy diet	Encouraging patients to consume increased amounts of fruit and vegetables For obese asthma patients, include weight reduction in the treatment plan in the form of aerobic or strength exercises Encouraging patients to avoid food chemicals when food chemical sensitivity or food allergy is confirmed; otherwise, food avoidance is not recommended	General health benefits, certain fruits and vegetables help reduce inflammation Exercise is more effective in symptom control than weight reduction alone
Eliminating emotional stress or anxiety	Encourage patients to identify goals and strategies to deal with emotional stress Encourage patients to involve relaxation strategies and breathing exercises in their daily routine Encourage patients to obtain professional help if necessary	Reduced risk of symptoms and exacerbations

(Own elaboration according to GINA 2024). ICS: Inhaled corticosteroid, SABA: Short-acting inhaled β2 agonist bronchodilator missing check word file

Pharmacological treatment consists of maintenance treatment, controllers and relievers, anti-inflammatory reliever (AIR), and maintenance and reliever therapy (MART).[8,9] Maintenance treatment is prescribed for everyday use, even though a person does not have asthma symptoms, as the medication is intended to be used continuously. They include ICS-containing medications (ICS, ICS-LABA, ICS-LABA-LAMA), leukotriene receptor antagonist [LTRA], and biologic therapy).[4,10,11]

Controllers can be defined as basic anti-inflammatory drugs administered regularly, which are intended for daily long-term use.[12] They provide asthma control through an anti-inflammatory effect and target both domains of asthma control (symptoms and future risk). Another solution is antileukotriens in tablet form. The onset of action of the drugs is not immediate.[13,14] Relievers are taken only when there is difficulty (difficulty breathing, wheezing, chest heaviness). They have a bronchodilating effect and remove the symptoms of the disease. Relief comes quickly after taking relievers, but they do not cure chronic inflammation. Increased use of relievers is a signal of worsening asthma symptoms.[5,15,16,17,18] Treatment of asthma involves a combination of medications – controllers and relievers.

The relievers consist of the anti-inflammatory component ICS-formoterol and the ICS-SABA and SABA combination.[19] They are often recommended as a short-term treatment when bronchoconstriction occurs. The use of relievers via inhalation technique is considered the fastest way to bring relief from breathing difficulties, worsening asthma, or exacerbations, because it provides targeted delivery of the drug, is faster acting, requires a small dose, and is easy to take.[20,21] Very important is how much of the drug reaches the target organ. This depends on the correct inhalation technique, the characteristics of the inhalation system, and the size of the emitted particles. Oral steroids have more side effects and do not have superiority over ICSs in the management of asthma. However, they are more beneficial in the management of severe acute exacerbations.[4,22,23,24]

An AIR is an inhaler that contains a low dose of ICS and a rapid-acting bronchodilator. Patients can also use it before exercise, other physical activity, or exposure to allergens as a prevention against bronchoconstriction or worsening of symptoms.[25,26,27]

Maintenance and reliever therapy (MART) is used only with combination ICS-formoterol inhalers such as budesonide-formoterol and beclomethasone-formoterol. MART treatment means that the patient takes ICS-formoterol every day (as a maintenance dose) and, if necessary, a releaser.[28,29]

Treatment with antihistamines can be administered in adult patients by inhalation, orally or parenterally (subcutaneously – administered subcutaneously, intramuscularly – administered into the muscle, or intravenously – administered into a vein). Inhaled antihistamines come in the form of metered-dose aerosol inhalers, which can be triggered by pressure or inhalation, powder inhalers, fine particle inhalers, and nebulizers. They vary depending on the type, drug molecule, aerosol cloud velocity, and the degree of ease of handling the inhaler.[15,30,31]

When using a releaser, proper inhalation technique is key. There are two basic types of inhalation devices: pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs).[32] The inhalation technique is similar in both cases; we first remove the cap of the inhaler. In the case of pressurized dose inhalers, we shake the inhaler before use. For DPIs, we make sure that the device is filled.[33] Next, exhale gently and insert the mouthpiece between the lips, wrapping it tightly around the lips. Activate the inhaler and inhale deeply. Hold your breath for five to ten seconds, then slowly exhale. Repeat the process if necessary. Then put the inhaler cap back on.[34]

MEDICATIONS FOR MAINTENANCE TREATMENT

ICSs – beclomethasone, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate, mometasone, triamcinolone – are the most effective medications for asthma control.[35] They suppress inflammation mainly by switching off several activated inflammatory genes by reversing histone acetylation through the recruitment of histone deacetylase 2. By suppressing airway inflammation, ICS reduces airway hyperresponsiveness and controls asthma symptoms; most patients do not experience side effects. They are currently the first-line treatment of choice for all patients with persistent asthma as they control asthma symptoms and prevent exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers to improve any complications and control asthma at lower doses of corticosteroids.[36,37,38]

ICS in combination with long-acting beta₂ agonist bronchodilator (ICS-LABA) – beclomethasone-formoterol, budesonide-formoterol, fluticasone furoate-vilanterol, fluticasone propionate formoterol, fluticasone propionate-salmeterol, mometasone-formoterol, mometasone-indacaterol – improves symptoms, lung function, and reduces exacerbations more rapidly than a double dose of ICS.[39] There are two known methods of combination. The first is a low-dose combination of beclomethasone or budesonide with low-dose formoterol (maintenance and reliever treatment), and the second is maintenance ICS-LABA with SABA or ICA-SABA as a reliever.[40,41] However, the LABA component may cause side effects as tachycardia, headache, or cramps. Combination with ICS is safe for asthma patients.[4,42]

Leukotriene modifiers (LTRAs), montelukast, pranlukast, zafirlukast, zileuton, including cysteinyl LTRA (CysLT) and LTB4, are potent lipid mediators that are key in the pathophysiology of asthma phenotypes. At least, two receptor subtypes for CysLTs have been identified, CysLT1 and CysLT2. Most of the pathophysiological effects of CysLTs in asthma, including increased airway smooth muscle activity, microvascular permeability, and airway mucus secretion, are mediated by activation of the CysLT1 receptor. LTB4 may play a role in the development of airway hyperresponsiveness, severe asthma, and asthma exacerbations.[43,44] Although generally less effective than inhaled glucocorticoids, CysLT1 receptor antagonists can be administered orally as monotherapy in patients with persistent mild asthma. In patients with more severe asthma, CysLT1 receptor antagonists may be combined with inhaled glucocorticoids. This therapeutic strategy improves asthma control and allows the dose of inhaled glucocorticoids to be reduced while maintaining similar efficacy.[45,46,47]

ADD-ON MAINTENANCE MEDICATIONS

Long-acting muscarinic antagonists (LAMAs) – tiotropium, combination ICS-LABA-LAMA inhalers, beclomethasone-formoterol-glycopyrronium, fluticasone furoate-vilanterol-umeclidinium, and mometasone-indacaterol-glycopyrronium – improve lung function and modulate bronchial tone by blocking muscarinic acetylcholine receptor (mAChR).[48,49,50]

Anti-IgE – omalizumab – is the only approved anti-IgE monoclonal antibody in patients aged ≥ 6 years with uncontrolled moderate-to-severe (United States) and severe (European Union) allergic asthma as an adjunct to standard high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) therapy.[51] Omalizumab binds to free IgE in the Cε3 domain, the recognition site of the FcεRI receptor, inhibiting its interaction with effector cells and thus plays a key role in reducing both early and late phase allergic reactions. Omalizumab reduces the number of exacerbations and hospitalizations in hospitalized patients while improving both lung function and overall asthma control.[52] It has also been shown to have a positive effect in the context of oral corticosteroids (OCSs), which ultimately mitigates the side effects of OCS. The dosage and frequency of omalizumab are based on the total serum IgE level at baseline and the patient’s body weight using standardized dosing tables.[53,54,55]

Anti-IL-5 and anti-IL-5Rα – mepolizumab, reslizumab – is recommended for patients with uncontrolled severe eosinophilic asthma on high-dose ICS-LABA.[4]

Anti-TSLP – tezepelumeb – is an adjunctive therapy for patients with severe uncontrolled asthma on high-dose ICS-LABA.[56]

Systemic corticosteroids – prednisone, prednisolone, methylprednisolone, hydrocortisone tablets, dexamethasone – represent the primary therapeutic intervention for persistent asthma, along with other control therapies, including predominantly long-acting β2-agonists (LABAs) and LTRA, as adjunctive therapy to reduce ICS doses, control asthma symptoms, and reduce the risk of exacerbation in patients with asthma. Adjunctive therapy, traditionally with LAMA or low-dose OCS (prior to the introduction of targeted biologics – omalizumab), is recommended for patients with asthma that is not controlled with moderate to high doses of ICS plus control medications.[57,58] Short-term treatment (5–7 days) short-term treatment serves in acute exacerbations with an effect within 4-6 hours. OCS therapy is effective as prevention against short-term relapse. Long-term treatment with OCS is usually recommended for patients with severe asthma, but there is a risk of potentially serious side effects - diabetes, osteoporosis, glaucoma, and heart failure.[4,59]

ANTI-INFLAMMATORY RELIEVER MEDICATIONS

Low-dose combination ICS-formoterol – beclometasone-formoterol, budesonide-formoterol – is a treatment for patients who were prescribed MART with maintenance ICS-formoterol or as-needed-only ICS-formoterol. It reduces the risk of severe exacerbations with similar symptom control compared with SABA as a reliever. ICS-formoterol treatment reduces emergency hospitalizations by 65.00% compared with SABA and 37.00% compared with ICS plus as-needed SABA.[60] A low dose of ICS-formoterol may be taken prior to strenuous physical activity or exercise, due to precautionary reduction of bronchoconstriction or exposure to allergens to reduce allergic responses.[19,26]

Low-dose combination ICS-SABA – budesonide-salbutamol (albuterol-budesonide), beclometasone-salbutamol – is an anti-inflammatory option that reduces the risk of severe exacerbations compared with SABA relievers.[61]

SHORT-ACTING BRONCHODILATOR RELIEVER MEDICATIONS

SABAs – salbutamol (albuterol), terbutaline – provide quick relief of asthma symptoms and bronchoconstriction, and they may be used as prevention before physical activity or exercise. SABAs should be used only as-needed and at the lowest dose and frequency (not regularly).[62] This treatment only is not recommended for the possible risk of severe exacerbations and asthma-related death. Nowadays, SABAs are the most used bronchodilators for acute exacerbations.[63]

Short-acting antimuscarinics (anticholinergics) – ipratropium bromide, oxitropium bromide – may be used in combination with SABA. This type of medication is suitable for short-term treatment in severe acute asthma, when the addition of ipratropium to SABA significantly reduces the risk of hospitalization.[64,65]

CONCLUSION

In recent decades, the treatment of bronchial asthma has advanced significantly, not only due to a better understanding of the pathophysiology of the disease, but also to the discovery of new therapeutic strategies. Management based on an individualized approach in the control of the patient’s condition is key. ICSs remain the mainstay of long-term treatment, while their combination with long-acting β2-agonists (LABAs) significantly improves clinical outcomes. Biological therapies are coming to the fore, bringing significant advances in treatment for patients with severe eosinophilic or allergic asthma. Monoclonal antibodies such as anti-IL-E (omalizumab), anti-IL-5 (mepolizumab, reslizumab), or anti-IL-4/IL-13 (dupilumab) allow a personalized approach to therapy, thus achieving better disease control and reducing the need for systemic corticosteroids. Within the nephromacological form of disease management, an individualized approach to the patient is important, including patient education, elimination of triggers, and incorporation of physical activity into the patient’s daily routine. However, the challenge remains the identification of disease phenotypes and the development of therapeutic approaches targeting inflammatory processes occurring at the molecular level.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Funded by the EU NextGenerationEU through the Recovery and Resilience Plan for Slovakia under the project No. 09I03-03-V05-00006.