Introduction ¹

• Asthma is a heterogeneous disease of the respiratory tract characterized by chronic airway inflammation and affects 1-29% of world population.
• Symptoms mostly include wheeze, shortness of breath, chest tightness and or cough, and also variability in the expiratory airflow limitation.
• Variations depend on several triggers such as exercise, allergen or irritant exposure, weather change or respiratory infections due to viruses.
• Mostly symptoms resolve with treatment, but patients may experience episodic flare-ups or exacerbations which may be life-threatening.
• Clinical phenotypes might include: Allergic asthma Non-allergicAdult-onset Asthma with persistent airflow limitationAsthma with Obesity ¹

The goal of asthma management ¹

• Achieve good control of symptoms and maintain normal activity levels
• Minimize the risk of asthma-related death, exacerbations, persistent airflow limitation and side-effects
• Educating healthcare providers to enhance their communication which in turn could increase in patient satisfaction, better health outcomes and enhance patient adherence.
• Training patients and educating them with proper information about asthma management thus improving adherence with treatment recommendations.

Overuse of SABAs ²

Evidences: ^2,3

Asthma Management with Combination Therapy:

Combination therapy for asthma management involves using a combination of medications, typically an inhaled corticosteroid (ICS) and a bronchodilator, in a single inhaler. This approach targets both inflammation and bronchoconstriction, providing comprehensive control of asthma symptoms. For patients with mild persistent asthma, who make up about 70 percent of all asthma cases, low-dose inhaled corticosteroids are often used. Those with moderate asthma may require both an inhaled corticosteroid and a long-acting beta agonist.  ⁴

Research has shown that for patients with moderate to severe asthma, a combination of a low-dose inhaled corticosteroid and a long-acting beta agonist is more effective than using inhaled corticosteroids alone. Studies on patients with mild asthma suggest that these treatment options are similarly effective. ⁵

Key points:  ^6-8

Advantages of combination therapy vs monotherapy  ^4,9,10

Combination Therapy:

• Combination therapy can be used for both maintenance and relief in asthma management.
• Using combination therapy in a single device, simplifies treatment regimens and supports personalized care, making it an ideal strategy for primary care physicians and patients.
• It enhances patient adherence, reduces the complexity of dosage regimens, and improves therapeutic outcomes.

Monotherapy:

• SABA monotherapy (without ICS) may have harmful effects, including an increased risk of death²
• SABA monotherapy is a treatment strategy that does not address inflammation and may even exacerbate it.

Evidences showing benefits of combination therapy: ^11,12,13

• A study by Reynold et al (2024) revealed that In the US, asthma guidelines recommend using a short-acting β2-agonist (SABA) alongside an inhaled corticosteroid (ICS) as an alternative reliever at step 2 of treatment. The FDA has given the green light to a pressurized metered-dose inhaler that combines albuterol and budesonide, designed for on-demand treatment or prevention of bronchoconstriction, as well as lowering the risk of exacerbations for adults with asthma.¹¹
• In a phase 3, double-blind, randomized, event-driven trial involving 3,132 patients, the risk of severe asthma exacerbations was significantly reduced with the as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide, compared to as-needed albuterol alone. This finding was observed in patients with uncontrolled moderate-to-severe asthma who were already receiving various inhaled glucocorticoid-containing maintenance therapies.¹²
• in a pilot study conducted by Papi and colleagues, the effectiveness of symptom-driven beclomethasone dipropionate plus albuterol in a single inhaler was compared with the traditional approach of regular inhaled beclomethasone plus as-needed albuterol. The study included 455 patients with mild asthma, divided into four treatment groups: as-needed combination therapy, regular beclomethasone therapy, and regular combination therapy. The results showed that using beclomethasone/albuterol as a rescue inhaler was as effective as regular inhaled beclomethasone and was associated with a lower cumulative dose of inhaled corticosteroids (ICS) over six months.¹³

Conclusion:

• A single inhaler device comprising of combination therapy of a SABA and ICS such as  levosalbutamol and beclomethasone offers several benefits.
• Levosalbutamol activates β(2)-adrenoceptors, causing the airways to widen (bronchodilation). Beclomethasone decreases inflammation by reducing capillary permeability and stabilizing lysosomes. Together, they relieve symptoms and address the underlying inflammation, reducing the frequency and severity of asthma attacks.
• Administering SABA-ICS on an as-needed basis, particularly when asthma symptoms begin to worsen, can help lower the risk of exacerbations by providing both genomic and non-genomic anti-inflammatory benefits.
• Combination Therapy enhances patient adherence, reduces the complexity of dosage regimens, and improves therapeutic outcomes.
• Combination inhaler devices simplify treatment and enable a tailored approach to managing asthma, making it an excellent option for primary care physicians and patients.

References

1. POCKET GUIDE FOR ASTHMA MANAGEMENT AND PREVENTION: GINA; 2023 [cited 2024 1-Apr-24]. Available from: GINA Pocket Guide 2023 (ginasthma.org)…
2. Nwaru BI, Ekström M, Hasvold P, Wiklund F, Telg G, Janson C. Overuse of short-acting β(2)-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. 2020;55(4).
3. Stanford RH, Shah MB, DSouza AO, Dhamane AD, Schatz M. Short-acting β-agonist use and its ability to predict future asthma-related outcomes. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2012;109(6):403-7.
4. Saleh JA. Combination therapy in asthma: a review. Nigerian journal of medicine : journal of the National Association of Resident Doctors of Nigeria. 2008;17(3):238-43.
5. Monotherapy vs. Combination Therapy for the Management of Mild Asthma: Am Fam Physician. 2012;85(6):652; [cited 2012]. Available from: https://aafp.org/pubs/afp/issues/2012/0315/p652.html.
6. Reddel HK, Bacharier LB. Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes. 2022;205(1):17-35.
7. Asthma: Updated Diagnosis and Management Recommendations from GINA: Am Fam Physician. 2020;101(12):762-763; [cited 2024 2-Aug-2024]. Available from: https://aafp.org/pubs/afp/issues/2020/0615/p762.html.
8. Brunaugh AD, Sharma S, Smyth H. Inhaled fixed-dose combination powders for the treatment of respiratory infections. 2021;18(8):1101-15.
9. Asthma, Management and Treatment: CDC; 2023 [cited 2024 4-Apr-24]. Available from: https://cdc.gov/asthma/management.html.
10. Reynold A. Panettieri Jr. M, Bradley E. Chipps M, Neil Skolnik M, Maureen George R, PhD, Kevin Murphy M, Njira Lugogo M. The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations: Journal of Allergy and Clinical Immunology: In Practice; VOLUME 12, ISSUE 4, P882-888, APRIL 2024; 2024 [cited 2024]. Available from: https://jaci-inpractice.org/article/S2213-2198(24)00145-4/fulltext#%20.
11. Papi A, Chipps BE, Beasley R, Panettieri RA, Israel E, Cooper M, et al. Albuterol–Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. New England Journal of Medicine. 2022;386(22):2071-83.