Liam Harvey (Year 12

Asthma and an evaluation of the effectiveness of short acting bronchodilators as a method of treatment

Liam Harvey (Year 12) The Illawarra Grammar School, 10/12 Western Avenue, Wollongong, NSW, Australia, 2500

Introduction

According to the World Health Organisation (WHO) – a specialised agency responsible for monitoring and managing international public health, 262 million people in 2019 were impacted by bronchial asthma and its symptoms, resulting in over 460000 deaths globally. The most common treatment method for bronchial asthma is the use of an inhaled short-acting bronchodilator. In a changing world where technology is advancing, new industries and power solutions are producing more air pollutants than ever before. 95% of the world’s population experiences exposure to air particulates and pollutants that are above the WHO’s recommended guidelines of 10µg/m3 (Ritchie & Roser 2022). This constant and increasing exposure to unsafe concentrations of air pollutants and particulates is a factor that exacerbates the symptoms of asthma on those with the chronic condition, leading to more frequent application of treatment solutions (Asthma Australia, 2021). Due to this global increase in the air pollutant level into unsafe quantities that could be a trigger factor and impact those with asthma, an evaluation of the effectiveness of short acting bronchodilators is necessary to ensure their viability for the future.

Research Question + Sub Questions

The main, guiding research question for this evaluation is: Are short acting bronchodilators an effective treatment for bronchial asthma? To answer this main question, a range of sub-questions need to be addressed:

• What is bronchial asthma? • What are short-acting bronchodilators? • What are the measures of effectiveness of bronchodilators? • What are the technologies that can boost their effectiveness?

Asthma

According to the Global Initiative for Asthma (GINA): an international organisation that coordinates asthma control programs, research, and guidelines, and Asthma Australia: An Australian organisation that aims to assist and educate those with asthma, asthma is defined as a chronic noncommunicable disorder where common, characterising symptoms include:

• airway inflammation • constriction of airway muscles • bronchial hyperresponsiveness • wheezing • persistent cough • chest tightness • shortness of breath • excessive mucus production

Diagram 2: Diagram of the differences in a normal airway, an asthmatic airway, and a severely asthmatic

Symptoms of asthma can vary in duration and intensity, making diagnosis reliant on a case-by-case understanding and historical basis. More intense and severe symptoms can result in hospitalisations and death, as the person is unable to breathe. There are a range of common factors and triggers that can cause an episodic flare-up of asthma symptoms that can divide asthma into a range of factor phenotypes, including but not limited to (Asthma Australia 2021):

Phenotype

Allergic Asthma

Non-allergic Asthma

Occupational Asthma

Exercise-induced Asthma Nocturnal Asthma

Cause

Allergens including pollen, dust, and animal dander. Includes viruses (cold/flu), smoke and aerosol sprays (deodorants). Occupational triggers such as chemicals, fumes, and coal dust. Caused by exertion and physical activities Factors related to the night, such as dust mites and weather conditions

Specifically, regarding the pathophysiology of asthma and the body’s response to these factors, specific antibodies called Immunoglobulin E (IgE) are released due to the detection of one of these factors present in the environment or in the body. The IgE antibodies bind to mast cells, which are immune cells that control the release of inflammatory chemicals such as histamine, and causes them to release those chemicals, generating the symptoms of bronchoconstriction and inflammation, as they increase blood flow to the airways and cause the smooth muscle cells of the airway to contract (See Diagram 1) (Sinyor, B & Perez, LC 2021). According to the Australian Institute of Health and Welfare (AIHW) website – a government-run institute that provides meaningful information and statistics regarding health and welfare, 11% of the Australian population (2.7 million people) have asthma, as collected from 2017-2018. This means that 11% of the population is using some form of inhaled short-term bronchodilator to combat their symptoms of asthma, supporting the need for an evaluation of short-term bronchodilator effectiveness.

Inhalers

Short-acting bronchodilators, also known as asthma relievers, are medication that is fast-acting to quickly counteract the symptoms of asthma when they are exacerbated. Specifically, they relax the smooth muscle cells within the airway which contract when trigger factors occur in the environment. The most common bronchodilator chemical used in Australia is called salbutamol, and there are four main relievers that use this chemical: Ventolin, Asmol, Zempreon and Airomir (See Diagram 2) (Asthma Australia, 2021). These relieving inhalers are not to be confused with preventers, which are used every day to provide a baseline level of protection from symptoms. They are commonly composed of an aluminium canister with a blue/grey plastic housing (Asthma Australia, 2021). Chemically, relievers operate by dispersing the bronchodilator (in the case of the Diagram 2, salbutamol) as an aerosol – a gas with fine particles of the medicine dispersed inside of it. This Diagram 3: Image of the 4 most common will provide quicker access to the airways and the bloodstream, inhalers in Australia, all of which use which is where the salbutamol can take effect. This means that the medication will work within minutes, maximising relief salbutamol (Asthma Inhalers used in Australia, 2021) from symptoms and preventing further exacerbation. Salbutamol, also known as a beta-2 agonist, works by activating the beta-2 receptor. This receptor is present in a range of cell groups, including cardiac cells and smooth muscle cells – when activated in smooth muscle cells, it causes them to relax, and when activated in cardiac cells, leads to an overall increase in heart rate, according to research conducted by researchers from the Alexandria School of Medicine, and the University of Florida (Abosamak, N & Shahin, M 2021). Diagram 3: Image of a dry powder reliever Because of this, a potential side that uses terbutaline (Asthma Inhalers used in Australia 2021) effect of the use of salbutamol is an increase in heart rate, as the chemical cannot target specific cells – hence it may activate beta2 receptors in cardiac cells (Syed, SA, et al. 2021). Potential additions to current reliever technology include a powdered bronchodilator that is easier to use for those with inhibited use of aerosol relievers, called terbutaline (Figure 3), and spacer technology that increases the amount of bronchodilator that reaches and is absorbed into the airways (Figure 4).

Diagram 4: Image of a plastic spacer used to improve bronchodilator distribution in the airways (Spacer, 2021)

Prediction

Based on the background research conducted, it is predicted that inhaled short-acting bronchodilators are an effective method of treating bronchial asthma with minimal side-effects. Furthermore, it is predicted that technologies such as spacers can improve the effectiveness of inhaled short-acting bronchodilators delivered using current reliever technology.

Effectiveness of reliever’s in treating Asthma

The effectiveness of short-acting bronchodilator relievers will be measured using the following criteria:

• Long-term impact on asthmarelated hospitalisations since introduction of short-acting bronchodilators • Impact on variable lung function tests conducted through spirometry • Cost

A study conducted in Salvador City, Brazil by C. Souza-Machado, A, et al – a group of Brazilian researchers, found that there was an inverse relationship between the introduction of inhaled short-acting bronchodilator relievers as a method of asthma treatment and hence the number of asthmatic patients using inhaled short-acting bronchodilator relievers, and the hospitalisation rate per 10000 people. The study analysed data before and after the implementation of the ProAR program in the city, which dispensed 220889 units of inhaled reliever medication to those in need. The middle line of Figure 1 represents an 87.5% decrease in the hospitalisation rate of asthmatic patients in Salvador between 2002-2006. Figure 2 further illustrates the impact of relievers on the hospitalisation rate, with a drop from approximately 0.09% of asthmatic patients going to hospital in 2003, to approximately 0.02% in 2006.

Within Australia, according to the Australian Institute of Health and Welfare, there were 38792 hospitalisations in 2017-18 where the primary cause was asthma-related symptoms. According to Asthma Australia, the National Service Improvement Framework for Asthma was released in 2005 and was a significant step in improving the accessibility of and the quality of short-acting bronchodilator medication in Australia. Figure 3 shows the overall decrease in hospitalisations for both groups aged 014, and the fluctuations in hospitalisations for both groups aged 15+. It can be inferred that this decrease in hospitalisations was contributed to by this Framework, and hence the use of short-acting

Figure 1: Graph showing the impact of the ProAR dispensing program on the asthmatic hospitalisation rate in Salvador City. Asthmatic inhabitants are represented by the middle line, and the program was implemented in 2003 (represented by the arrow) (Souza-Machado, C, et al., 2009) Figure 2: Combination graph highlighting the inverse relationship between the number of patients enrolled in the ProAR dispensing program and the asthma hospitalisation rates per 10000) (Souza-

bronchodilators to combat the exacerbated symptoms of asthma. A decrease in hospitalisations correlates to an increase in the use of relievers to combat exacerbated symptoms. Spirometry is a method of assessing the function of the lungs: the amount of air that can be breathed in and out, how fast and how hard air can be breathed out at one time (Asthma Australia 2021). Asthma can impact the result of this; hence spirometry tests are a way to diagnose asthma but can also highlight the effectiveness of short-acting bronchodilators if spirometry tests are performed before and after the use of a bronchodilator, known as Bronchodilator Response (BDR) testing. A study conducted by Dr H A Thiadens, et al, from the Leiden University Medical Centre, Netherlands, found a weakmoderate correlation between the inhalation of 400µg of salbutamol through a reliever device, and an increase in Forced Expiratory Volume (FEV) – the amount of air a person can exhale within a set time period. The study determined that a positive bronchodilator response was classified as an increase in FEV during the first second of exhalation of 9% or more after having inhaled 400µg of salbutamol, compared to their FEV value before taking the bronchodilator. Within this study, 32 participants (13.3%) of the 240 participants had a positive bronchodilator response in accordance with the definition set out by the study. This supports the effectiveness of short-acting bronchodilators as they can successfully increase the amount of air a person can exhale by a minimum of 9% Another study conducted by Christer Janson, et al, used a similar definition for a positive bronchodilator response, but instead the study defined it as a minimum increase in FEV during the first second of exhalation of 12%, from the spirometry performed before and after the inhalation of 200µg of salbutamol. The study found that in the 2833 patients with asthma who participated in the study, 17.3% had a positive bronchodilator response. Both studies that were conducted contribute to the effectiveness of short-acting bronchodilators as a treatment for asthma symptom exacerbations. Figure 3: Graph highlighting the decreasing trend in hospitalisations per 100000 population in a range of groups (Australian

Figure 4: Extracted table data of the before and after FEV results after the inhalation of 200µg of salbutamol, across a control group (left column) and the current asthma group (right column). Both groups exhibit a slight increase in FEV, contributing to the effectiveness of short-acting bronchodilators in minimising symptoms and reversing smooth muscle cell constriction (Janson, C, et al, 2019)

Asthma relievers are an extremely cost-effective treatment and can save time and money compared to other treatment solutions, including hospital visits. The AIHW Disease Expenditure Database found that hospitals spent $204 million on Diagram 5: Left image shows a normal airway, and right image shows an asthmatic airway narrowed due to inflammation. Through use of bronchodilators, the airways would asthma and its related return to a state like the left image (Bronchial asthma image n.d.), expenses in 2015-16. However, asthma relievers are over-the-counter treatments (do not require a prescription) and can be purchased for at a minimum of $10 (Pharmacy Online 2022). Through effective use of a reliever, asthmatic patients would prevent their airway from inflammation and bronchoconstriction shown in Figure 9 and prevent the need for a potential hospital visit if symptoms become exceedingly exacerbated.

Assisting Technologies

A range of assisting technologies currently exist that can further improve on the effectiveness of short-term bronchodilator relievers. One such technology is the use of a spacer. As shown in Diagram 6, spacers work by first dispersing the bronchodilator into the air, making the inhalation more gradual, resulting in more of the medication getting into the lungs and airways where it is most effective (Asthma Australia 2021). Another method of short-acting bronchodilator delivery is through a Diagram 6: Diagram showing the difference in bronchodilator nebulizer, where the bronchodilator is distribution in the body, when using a spacer and not using a spacer on the reliever (Spacer, 2021) converted into a fine mist that can be inhaled normally. This method of delivery is employed on individuals who find inhaler devices difficult to use or have anatomical reasons (Asthma Australia 2021). However, studies have shown that nebulizers are less effective in delivery of medicine compared to inhalers with a spacer. In a data review conducted by Christopher J Cates, Emma J Welsh and Brian H Rowe, it was found that in the emergency department when children were presented for severe exacerbations of asthma, the average length of stay using a nebulizer for treatment was 103 minutes, whilst the average length of stay using a spacer and reliever was 73 minutes. Overall, spacers are an addition onto relievers that will improve their effectiveness through improving the delivery of the short-acting bronchodilator into the airways and lungs.

Conclusion

Based on the evidence found in this study, it can be concluded that short-acting bronchodilators are an effective method of treatment for exacerbated asthma symptoms. Furthermore, their effectiveness can be improved by utilising spacer technology.

Bibliography

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