Clinical Review of Salbutamol in Reversible Obstructive Airway Diseases

Chronic Obstructive Airway Diseases: The Rising Burden in India: India has a disproportionately high burden of chronic respiratory diseases. Reportedly, the contribution of chronic respiratory diseases to the total disability-adjusted life-years (DALYs) in India has increased from 4·5%in 1990 to 6·4% in 2016. Of the total global DALYs due to chronic respiratory diseases, 32% have been estimated to have occurred in India. COPD and asthma were responsible for 75·6% and 20% of these chronic respiratory disease-related DALYs. (1)

Chronic Obstructive Airway Diseases & the Indian Issues:

Reportedly, approximately 38 million people are living with asthma in India. The burden is higher among those living in households using solid fuels like firewood and kerosene. Smoking which is considered the main risk factor for COPD has different forms in the Indian context. The Global Adult Tobacco Survey (GATS) study reported that 26 % of non-smokers are exposed to Second-Hand Smoke (SHS) at the workplace both indoors and outdoors in India. (2)

Cigarettes and other traditional forms of tobacco smoking including "hookah" and "chillum" are pervasive across different parts of India. Another source of smoke very common among Indian women is through the use of biomass fuels like cow dung and wood for cooking foods. Seventy percent of the Indian households depend on biomass cooking and the rate goes up to 84% in some of the rural parts of the country. Smoke emitted through biomass use, actively or passively, can be a leading cause of COPD among non-tobacco users. Air pollution and other environmental risk factors continue to be other major contributory risk factors in India. (3)

Therapeutic Use of Salbutamol in Obstructive Airway Disease to Help Open Airways – Review of Scientific Evidence

Salbutamol in Bronchial Asthma – Recommendations from Indian Medical Association

The Indian Medical Association recommendations on the management of bronchial asthma in primary care settings have been cited regarding the therapeutic utility of salbutamol in the management of bronchial asthma. It is recommended that non-severe exacerbations of bronchial asthma can be initially managed with inhaled salbutamol; 4-6 puffs of 100 μg administered every 30 minutes. (4)

Place of Salbutamol in Bronchial Asthma Management: Indian Guidelines

The two foremost authorities of respiratory medicine in India - the Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) collaboratively published the Joint ICS/NCCP recommendations for the management of bronchial asthma; have put forward the following statements in the context of clinical application of Salbutamol:

Rapid‑acting inhaled beta‑2 agonists (salbutamol) are the bronchodilators of choice for managing acute exacerbation of asthma.

In non‑severe exacerbations of bronchial asthma, patients should be initially managed with inhaled Short-acting beta-agonists (SABA). This could include 4‑6 puffs of 100 µg salbutamol every 30 minutes.

SABAs like salbutamol is the recommended agent of choice for rescue medication in stable asthma. (5)

Single Dose Salbutamol in Mild to Moderate Asthma – An Indian Experience

Jantikar A et al. published a study comparing the time-dependent bronchodilator responses of single doses of 100 mcg levosalbutamol and 200 mcg racemic salbutamol administered via a pressurized metered-dose inhaler (pMDI) in subjects with stable mild-to-moderate bronchial asthma over 6 hours. Single doses of 100 mcg levosalbutamol, 200 mcg salbutamol, and placebo were administered with a pMDI in thirty stable asthmatic subjects in a randomized, double-blind, placebo-controlled, three-way cross over study. Forced expiratory volume in 1s(FEV1) and forced vital capacity (FVC) were measured at baseline, and over 6 hours post-study drug administration. The study results demonstrated that salbutamol and levosalbutamol produced significantly better bronchodilator responses than placebo. Both the drugs showed equivalent time-dependent bronchodilator responses as measured by area under the curve for percent change in FEV1 and FVC over 6 hours. The time to onset of action, mean maximum, and duration of bronchodilator response were similar in the salbutamol and levosalbutamol treatment arms. It was thus concluded salbutamol produced a similar bronchodilator response in comparison to a single dose of 100 mcg levosalbutamol administered by a pMDI measured over 6 hours among patients with stable, mild-to-moderate bronchial asthma. A single dose of 100 mcg levosalbutamol administered by a pMDI produced a similar bronchodilator response as salbutamol when measured over 6 h in subjects with stable, mild-to-moderate bronchial asthma. (6)

Salbutamol for Use in Asthma- Effective and Safe for Therapy Certain clinical investigators had suggested that regular use of inhaled bronchodilators may lead to deterioration in asthma control. To challenge this hypothesis, Apter A et al, conducted a study to evaluate the effect of Salbutamol dosing schedule on clinical outcomes in subjects with moderate to severe stable asthma. Seventeen adults were randomized to two 15-week treatment periods in a double-blind crossover design. Throughout the study, patients were instructed to take two inhalations four times daily from an unlabelled 'test' canister. In the four times daily and as-needed (QID+PRN) period, this canister contained salbutamol; in the as-needed (PRN) period, it contained a placebo. A 'rescue' salbutamol canister was available for as-needed use at all times. The results of this study demonstrated that the two treatment periods did not differ in symptoms, night-time salbutamol use, or asthma-associated quality of life. During the (QID +PRN)phase, both morning and evening peak expiratory flow(PEF) rates were significantly higher (p < 0.01 and 0.001, respectively), and total rescue use of salbutamol was significantly lower (p < 0.05) as compared to the (PRN) period. It was thus concluded that in patients with moderate to severe asthma, four times daily dosing of salbutamol led to the achievement of better pulmonary function indices and effective asthma control. (7)

Salbutamol in Exercise-Induced Bronchospasm – Benefits in Paediatric Population

In a double-blind placebo-controlled crossover study conducted by Pedersenet al, among twenty-four asthmatic children treated with salbutamol 200 mcg administered from a dry powder inhaler and terbutaline 250 mcg delivered by a pressurized aerosol with a tube spacer. FEV1 was measured during the acute attack (pre-treatment FEV1) as well as 5 and 10 min after intervention. Ten minutes after salbutamol treatment, the improvement reported in FEV1 was 21%. It was demonstrated that both treatment interventions led to the same degree of protection against exercise-induced bronchospasm. (8) The duration of protection from exercise-induced asthma by inhaled salbutamol 200 mcg has been reported up to 6 hours among stable asthmatic patients. (9)

Clinical Utility of Salbutamol in COPD Exacerbations - Improved Pulmonary Function from Salbutamol Based Combination Treatment

Tashkin D.P. et al, conducted a study to examine acute bronchodilator responsiveness of salbutamol containing inhaled therapies in a large cohort of patients with moderate-to-very-severe COPD participating in the UPLIFT* trial. After wash-out of respiratory medications, patients received the intervention of 80 mcg ipratropium followed by 400 mcg salbutamol. Spirometry was performed before and 90 minutes following ipratropium administration. The criteria used for forced expiratory volume in one second (FEV1) responsiveness were: >12% increase over baseline and >200 mL; >15% increase over baseline; and >10% absolute increase in the percentage predicted value. A total of 5,756 patients had data meeting the criteria for analysis. The median age of this group was 64.5 yrs., comprised of 75% males; and had baseline FEV1 1.10 L (39.3% predicted) and forced vital capacity (FVC) 2.63 L. Compared with baseline, mean improvements were 229 mL in FEV1 and 407 ml in FVC. Of these patients, 53.9% had >12% and >200 mL improvement in FEV1, 65.6% had >15% improvement in FEV1, and 38.6% had >10% absolute increase in FEV1% predictive value. The majority of patients with moderate-to-very-severe chronic obstructive pulmonary disease demonstrated increases in pulmonary function indices following administration of inhaled salbutamol containing combination therapies.(10)

Concluding Message for Clinicians

Chronic Obstructive Airway Diseases are a huge burden and remain a major cause of disability in India. (1) This is largely due to environmental factors like pollution and the domestic habits of the Indian population. (3) Salbutamol, since its introduction, has become well established in the treatment of bronchospastic diseases. Salbutamol may be considered as in the initial treatment of mild to moderate asthma exacerbations among adults, adolescents, and children aged 6-11 years of age. (11)Inhaled salbutamol is extensively utilized due to its rapid onset of action and could be considered of clinical value in the treatment or prevention of bronchospasm and prevention of exercise-induced bronchospasm in adults and pediatric patients with reversible obstructive airway disease. (12)

*UPLIFT: Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT)