Asthma is a chronic respiratory condition that can be life threatening as it affects the lungs and can been seen in both paediatrics and adults. Asthma affects about 2 million Australians and over 400 Australians die each year from asthma (National Asthma Council Australia, 2006). It is a very serious condition that sees both emergency services personal and emergency departments regularly for treatment and management. Asthma is a hyperactive airway which can be triggered by either extrinsic or intrinsic factors. It usually results in bronchoconstriction, inflammation of the airways and excess mucus production. Patients present with shortness of breath, chest tightness and noticeable wheezing sound when breathing that can be auscultated by health care professionals. It is a condition that is normally diagnosed in childhood and can continue throughout adulthood. In this clinical review we will look at the pathophysiology of asthma, current protocols and treatments for asthma from both a state level to international level, how the current medications work, current research and possible new medications and see if there needs to be any changes to the current to the current asthma protocols.
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To review the current guidelines and protocols for adults, I have chosen to look at the Queensland Ambulance Service (QAS) asthma protocols, Victoria Ambulance Service and the United Kingdom's Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines. By looking at these 3 treatments and management guidelines we can assess how the QAS manages asthma compared to the rest of the Australia and the world.
Asthma is a life threatening condition that starts due to a hyperactive airway that has the characteristic of inflammation, reversible bronchoconstriction and excess mucus production. It has been traditionally been broken into two types Extrinsic and Intrinsic.
"Extrinsic asthma is when there is a type 1 hypersensitivity reaction which is initiated by an extrinsic allergen" (Cameron, Jelinek, Kelly, Murray, & Brown, 2009, pp. 279). This allergen then binds to immunoglobin E (IgE) which activates the degranulation of mucosal mast cells. As a result of the degranulation there is a release of primary and secondary mediators. Primary mediators are eosinophillic, histamine and neutrophilic chemotactic factors and the secondary mediators include platelet-activating factors, protsglandin D2, leukotrienes and cytokines (Cameron el at., 2009). These result in an increase of mucous secretions, airway smooth muscle constriction (bronchospasm) via direct and cholinergic reflex actions and an increase vascular permeability (Cameron el at., 2009).
Intrinsic asthma it is usually brought on by diverse non-immune mechanism. The most common form of stimuli is a viral respiratory infection. Other forms of stimuli are emotion, exercise, pollutants, occupational exposure and drugs such as Aspirin and beta blockers (Tintinalli et al., 2011).
An asthmatic episode, normally called an 'asthma attack' can have patients presenting with dyspnoea, chest tightness, expiratory wheezing and non productive coughing. Asthma has four levels of severity ranging from mild to life threatening/near death.
In the Queensland Ambulance Service the current drug therapy for Asthma is Oxygen, Salbutamol, Ipratropium Bromide and Adrenaline for their Advance Care Paramedics. For the Intensive Care Paramedics they are also allowed to administer Hydrocortisone and Magnesium Sulphate (Queensland Ambulance Service, 2011). The Victoria Ambulance Service their Qualified Paramedics are allowed to administer Oxygen, Salbutamol, Ipratropium Bromide and Adrenaline where as the Mobile Intensive Care Paramedics (MICA) have the ability to administer Dexamethasone (Victoria Ambulance Service, 2012).
Under the United Kingdom's Joint Royal Colleges Ambulance Liaison Committee (JRCALC) the latest guidelines are from October 2006. The medications they use for Asthma is Oxygen, Salbutamol, Ipratropium Bromide, Hydrocortisone and Adrenaline (JRCALC, 2006). All of these drugs are usually administered the same way, nebulised, intramuscularly, intravenously or by intraosseous. The doses are majority the same across the board, however there are some mild differences.
Salbutamol is a short acting beta-adrenergic agonist and is the front line drug that is administered for Asthma, it is also known as Albuterol or Ventolin. It is a beta-2 agonist that is a sympathomimetic mediation that targets the beta-2 adrenergic receptor. This stimulation promotes "bronchodilation, vasodilatation, uterine relaxation and skeletal muscle tremor" (Tintinalli et al., 2011, pp. 504). "Bronchodilation occurs by stimulation of the enzyme adenyl cyclise, which in turn, converts intracellular adenosine triphosphate into cyclic adenosine monophosphate" (Tintinalli et al., 2011, pp. 505). This action results in the relaxation of bronchial smooth muscle by reducing the myoplasmic calcium concentration by binding intracellular calcium to cell membranes (Tintinalli et al., 2011).
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Ipratropium Bromide is an anticholinergic agent which is also called Atrovent. It is normally administered with Salbutamol as they both complement each other, Anticholinergic work on the larger airways while the beta-adrenergic dilates the smaller airways. The action provided by this drug is that it antagonises the acetylcholine receptor on bronchial smooth muscle producing bronchodilation. It does this by blocking the vagal cholinergic-mediated innervations to the larger central airways which induces bronchoconstriction (Tintinalli et al., 2011).
Both Hydrocortisone and Dexamethasone are a corticosteroid and are a highly effective, in treatment of the exacerbations of asthma. The actual mechanism of action in a corticosteroid is unknown; however it is believed that they produce beneficial effects by reducing inflammation by "inhibiting the production of a number of mediators including prostaglandins, thromboxanes and leukotrienes" (Long, Bendall, & Bower, 2009). It is also believed that it restores beta-adrenergic responsiveness by increasing the sensitivity of the beta-receptors on the bronchial smooth muscle. Corticosteroids have shown to reduce hospital admission rates, decrease relapse rates and possibility reduce the number of fatal asthma cases. Administration of corticosteroids should be instituted early due to benefits not seen usually until 6-24 hours after administration (Holley & Boots, 2009).
Adrenaline is classified as an adrenergic agent and as a sympathomimetic. It is a naturally occurring catecholamine which acts on both the alpha and beta adrenergic receptors which are located mainly in the tissues innervated by sympathetic nerves (QAS, 2011). The alpha 1 receptors are located in the peripheral blood vessels and when stimulated produce vasoconstriction and an elevation of systemic blood pressure. Beta-1 receptors are cardiovascular in nature and are found within the heart. When these receptors are activated they cause an increase of heart rate, increase of the force of myocardial contraction and an increase of ventricle irritability. Receptors of bronchial smooth muscle are beta-2 receptors. Stimulation of these receptors results in the relaxation of smooth muscle and increase the diameter of the bronchial tree which induces bronchodilation (Guy, 2010).
Magnesium Sulphate is an electrolyte and is indicated for very severe asthma. It is suggested that the mechanism of action is by preventing the uptake of calcium ions into smooth muscle cells which induces a bronchodilator effect (Rogers & Reilbman, 2011). It is also believed that it reduces the neutrophil respiratory burst associated with asthma as an anti- inflammatory effect (Cameron et al., 2009). However the exact mechanisms of action still remain unclear.
Currently there are a multiple varieties of different medications for asthma. Apart from the ones stated above, other research into medications include Aminophylline, Heliox, Long Acting Beta agonists (LABA), Leukotriene inhibitors and even Ketamine. Discussed below are the medications that were found in recent research articles.
One direction that pharmaceutical companies are pursuing is in long acting beta-2 Adrenoceptors agonists (LABA). They are looking for a medication that is fast acting and that lasts for a full 24 hour action of duration with potential cardiac effects to be minimal. These medications are being labelled as Ultra-LABA. Currently listed are medications such as, Indacaterol, Olodaterol, Vilanterol, 38 (PF-610355) and Carmoterol. Current research studies compare the current LABA such as Formoterol and Salmeterol versus the upcoming Ultra-LABA's (Cazzola, Calzetta, & Matera, 2010).
Studies with Indacaterol, "human bronchi and small airway lung samples showed that it behaves as a high efficacy beta-2 adrenoceptor agonist and that it is not significantly different from Formoterol and Salbutamol but it is faster than Salmeterol and has a longer duration of both Formoterol and Salmeterol" (Cazzol et al., 2010, pp. 7). "Vilanterol is also a potent, selective beta-2 adrenoceptor agonist and has a greater intrinsic efficacy than Salmeterol and a greater potency than Indacterol and Salbutamol" (Cazzol et al., 2010, pp. 9). When administered to conscious guinea pigs as a nebulised solution, Vilanterol inhibited histamine-induced bronchoconstriction. It has been tested in both Asthmatic and COPD patients producing a rapid and prolonged bronchodilation over 24 hours (Cazzol et al., 2010).
Another area that is getting developed is intravenous B2-adrenoceptor agonists. One such medication is Bedoradrine or MMN-221. It is a highly selective for beta-2 adrenoceptors under development for exacerbations of acute asthma episodes and COPD. One study has evaluated that it was safe and appeared to provide addition clinical benefit via an intravenous infusion for patients with mild to moderate asthma (Cazzol et al., 2010).
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In one journal I found put the current medication Salbutamol against a long acting beta agonists, Procateral. The study was a randomized, double blind and parallel group study for the efficacy and safety of nebulised Procaterol versus nebulised Salbutamol in the moderate acute asthmatic patient. The results were that both medications where well tolerated, adverse reactions were lower in Procaterol than Salbutamol however were rare and that both drugs showed similar efficacy throughout the study (Muangunnegoro, Novariska, Wiyono, Setiawati, & Louisa, 2011).
Heliox is a gas that potentially can decrease the work of breathing in situations where there is an increased airway resistance like asthma. It is because of the low density compared to air as a Heliox mixture is about 80% helium and 20% oxygen. It was shown to "improve pulmonary function in one subgroup of patients with the most severe baseline pulmonary function impairment, but this was based on a small number of studies" (Holley & Boots, 2009, pp. 264). In the same article it states that even after 10 trials, Heliox showed no significant difference in the outcome of patients who were treated with it. Even though it may increase pulmonary function and is safe to use for severe asthmatics. It requires more research to fully evaluate this treatment.
Another area that also is being investigated is the use of Leukotriene receptor antagonist (LTRA), e.g. Montelukast. According to Cameron et al. (2009, pp. 281) "Leukotriene receptor were developed in response to the finding that leukotrienes exhibit biological activity that mimics some of the clinical features of asthma and are found in increased amounts in patients with asthma, especially during exacerbations". In one study it was found that LTRA was equivalent as a first-line controller therapy to an inhaled glucocorticoid and to a LABA as add-on therapy for diverse primary care patients (Price et al., 2011). Patients that received a LTRA received less B-agonists and fewer treatment failures than patients receiving the placebo and that in addition to standard therapy produces a rapid benefit. It is well tolerated in adults and could prove to be an adjuvant to current therapy, but at time of the current article the I.V preparation was not available in Australia (Holley, 2009).
The management for asthma from all accounts so far seems to be the most proactive for the patient. By having the current protocols of current drug therapy of Salbutamol, Ipratropium Bromide, a Corticosteroid, Adrenaline and Magnesium Sulphate. The treatment and management of Asthma is well looked after in the Pre-hospital setting. This helps not only the patient but also hospital waiting times and discharge times by having the patient treated faster and correctly by paramedics around the world. For the foreseeable future, research into Asthma needs to continue to find new treatment and possibly new medications that are more effective than the current model. More clinical trials are needed to see if there are any ways the current management can be more productive. However at this point in time Asthma protocols should stay the same and continue to help the public by reducing the effects of this dangerous condition.