This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.
In Western countries, asthma is one of the most common chronic disorders. It often manifests during childhood and its prevalence in children and adults is around 14% and 8% respectively. This equates to approximately 5 million of the population of United Kingdom. As a consequence, it is estimated that the yearly healthcare expenses of the UK is close to £3 billion.3
Asthma is defined as a chronic disorder, which involves the inflammation of the airways, resulting in repeated episodes of breathlessness, wheezing, tightness of the chest, and coughing in individuals who are susceptible.15 These repeated episodes may differ during the day (deteriorate during beginning and end of day) and may be precipitated by cold air, exercise, allergens (pollen) or drugs (non-steroidal anti-inflammatory drugs, or beta-blockers).1 They are due to obstruction of airflow which is often reversible, either spontaneously or when treatment is used.2
Airflow obstruction is due to inflammation of the airways, which ultimately results in changes of the airways, leading to bronchoconstriction, (contraction of smooth muscle of the bronchial precipitated by stimuli), bronchial hyperresponsiveness (exaggerated contraction of smooth muscle of bronchial) and airway oedema (hypersecretion of mucus which obstructs airflow).5,15
Bronchial hyperresponsiveness occurs as a result of an inflammatory process whereby inflammatory mediators are released from mass cells, eosinophils, neutrophils, monocytes and macrophages. The release of mediators such as histamine causes an immediate bronchial reaction whereas release of other mediators such as prostaglandin and leukotrienes (metabolites of arachidonic acid from both the cyclo-oxygenase and lipoxygenase pathway) produce a more sustained bronchoconstriction.4 These mediators interact to increase secretion of mucus which is hard to dislodge and damages the ciliated epithelium. When the protective epithelial barrier is breached, hyper-reactivity occurs resulting in bronchoconstriction, breathlessness and wheeze. Asthma is a polygenic/atopic disorder whereby those with a genetic loci for increased production of IgE have an increased incidence of asthma.4
Diagnosis of chronic asthma is made primarily by a history of recurrent episodes of breathlessness, wheezing, tightness of chest, coughing, and confirmation using a spirometry. A history of increased symptoms precipitated by stimuli also suggests asthma. Asthma is usually confirmed when spirometry demonstrates obstruction in airflow FEV1(forced expiratory volume in 1 second, FEV1/forced vital capacity of less than 80%) with reversibility after administration of inhaled beta2-agonist (≥12% improvement in FEV1).2
There are three types of acute asthma; moderate acute asthma, severe acute asthma, and life-threatening acute asthma. Diagnosis of these types of asthma is summarized in Table 1.
Table 1: Diagnosis of acute asthma
Moderate acute asthma
Severe acute asthma
Life-threatening acute asthma
Able to talk
Respiration < 25 breaths per min; CHILD 2-5 years ≤ 50 breaths per min; 5-12 years ≤ 30 breaths per min
Pulse < 110 beats per min; CHILD 2-5 years ≤ 130 beats per min; 5-12 years ≤ 120 beats per min
Arterial oxygen saturation ≥ 92%
Peak flow > 50-75% of predicted or best
Cannot finish sentences in one breath
Respiration ≥ 25 breaths per min; CHILD 2-5 years > 50 breaths per min; 5-12 years > 30 breaths per min
Pulse ≥ 110 beats per min; CHILD 2-5 years > 130 beats per min; 5-12 years > 120 beats per min
Arterial oxygen saturation <92%
Peak flow 33-50% of predicted or best; CHILD 5-12 years < 50% of predicted or best
Send immediately to hospital
Feeble respiration, cyanosis, hypotension, bradycardia, arrhythmia, confusion, reduced level of consciousness, or coma
Arterial oxygen saturation <92%
PaO2 < 8 kPa
Peak flow < 33% of predicted or best; CHILD 5-12 years < 33% of predicted or best
Send immediately to hospital; refer for intensive care
Adapted from 1,6
2. Pharmacological basis of drug therapy
2.1 Anticholinergics and short acting beta2 agonists
Patient with acute exacerbation of asthma was started with nebulised A:V:N (2:1:2) which was Atrovent (ipratropium bromide), Ventolin (salbutamol) and normal saline in the volume ratio of 2:1:2. She was also given MDI salbutamol 2 puffs when required for occasional relief of symptoms for chronic asthma.
Ipratropium bromide is an anticholinergic.4 Anticholinergics are effective bronchodilators but are less potent than beta2-agonists.2 Its mechanism of action is by competitively inhibiting the receptor of acetylcholine at vagal nerve endings that constrict bronchial smooth muscle,4,15 producing bronchodilation only in bronchoconstriction which is cholinergic-mediated.2 The most common side effect of anticholinergic bronchodilators is dry mouth, followed by nausea, headache, and constipation.6
Salbutamol is a short-acting beta2-agonist. Short-acting beta2-agonists are the most effective bronchodilators available. Their mechanism of action is by stimulation of the beta2 adrenergic receptors, which then activates adenyl cyclase, producing an increase in intracellular cyclic adenosine monophosphate, which results in smooth muscle relaxation and mast cell membrane stabilization. They are indicated for relieve of recurrent episodes of bronchospasm and thus, are only used when required.2 Side effects include tremor, nervousness, headache and palpitation.6
Patient was also started on IV hydrocortisone 100 mg four times a day, which was subsequently replaced by prednisolone tablets 20 mg once daily, both of which are corticosteroids used for management of acute exacerbation of asthma. She was also given MDI beclometasone dipropionate, a corticosteroid, 2 puffs twice a day, for the long-term control of her chronic asthma. The mechanism of action of corticosteroids is by two ways; increasing the number of beta2-adrenergic receptors and improving receptor responsiveness to stimulation of beta2-adrenergic receptors. As a result, there would be reduced hypersecretion of mucus, bronchial hyperresponsiveness and airway oedema.2 Side effects such as reduction in bone mineral density and adrenal suppression are more common in higher doses of inhaled corticosteroids.6,14
Patient was also started on bromhexine hydrochloride tablets 8 mg three times a day. Bromhexine hydrochloride is a mucolytic, and its mechanism of action is by reducing the viscosity of the mucus secretions, breaking down mucus, and aiding its clearance through coughing.7
3. Evidence for treatment of the condition(s)
3.1 Acute Asthma - Salbutamol (short-acting beta2 agonist) and ipratropium bromide (anticholinergic) via nebulizer
According to the SIGN 101 British Guideline on the Management of Asthma, management of acute asthma involves giving inhaled short-acting beta2 agonist via a large-volume spacer or oxygen-driven nebulizer (4-10 puffs salbutamol 100 µg/metered inhalation or nebulised salbutamol 5 mg) and adding ipratropuim bromide, 500 µg also via oxygen-driven nebulizer if patients' response is poor.1 Patient was given Atrovent:Ventolin:Normal Saline in the ratio of 2:1:2 in terms of volume, through the nebulizer. 1 ml of Ventolin respirator solution (5 mg/ml) consisted of 5 mg of salbutamol sulphate while 2 mls of Atrovent nebulizer solution (250 µg/ml) consisted of 500 µg of ipratropium bromide, which was in accordance to the BNF.6 A meta-analysis of 10 studies which were double-blind, randomized, controlled trials, and which consisted of a total number of 1483 patients who were having acute asthma and who were treated with short-acting beta2 agonist with/without addition of ipratropium bromide in the emergency department were studied. Results revealed significant benefit from treatment with additional ipratropium where the pooled effect size of pulmonary function was 0.14, p<0.01 and indicated a 10% increment in FEV1 or PEFR which favoured the group treated with ipratropium as compared to the control group. Pooled results from 4 trials revealed that additional treatment with ipratropium in patients who had FEV1 of less than 35% had significant improvement while pooled results from 5 trials revealed that ipratropium therapy in conjunction with short-acting beta2 agonist significantly reduced rates of hospital admission, p<0.01.11
Another meta-analysis conducted confirmed the effectiveness ipratropium therapy with short-acting beta2 agonist in acute asthma. It also compared the effectiveness of short-acting beta2 agonist with ipratropium or a short-acting beta2 agonist on its own for treatment of patients with acute asthma. 32 RCTs were included and results indicated significant decrease in incidence of admission to hospital in children and adults, p = 0.0001 and p = 0.002 respectively and significant rise in parameters measured by spirometry after 1-2 hours in children and adults who were treated with combined therapy.16
3.2 Acute Asthma - Oral prednisolone or intravenous hydrocortisone
According to the SIGN 101 British Guideline on the Management of Asthma, management of acute asthma involves treating with prednisolone 40-50 mg or intravenous hydrocortisone 100 mg. Patient was initially started with IV hydrocortisone 100 mg four times a day upon admission and it was then replaced by prednisolone 40 mg when patient was stabilised.
A meta-analysis of 30 RCTs was conducted where results showed that treatment of acute asthma exacerbations with systemic steroids resolved the acute asthma quicker, reduced hospital admissions in both adults and children and was effective in the prevention of relapse in those who were treated as outpatients. It was found that both forms of administration of steroids, oral or intravenous had similar effects on pulmonary function in the treatment of acute exacerbation of asthma.12
A Cochrane review of 6 RCTs was conducted to determine the effectiveness of systemic corticosteroids (oral, IV, IM) in the treatment of severe acute asthma patients when administered in higher doses as compared to lower doses. Corticosteroid dose was divided into three catagories; low (≤80 mg), moderate (>80 mg but ≤360 mg) and high (>360 mg). These doses were the equivalent doses of prednisolone per day. Results at 24, 48 and 72 hours among the 3 groups of varying doses revealed no clinical or statistical significance in the differences in % FEV1 predicted. As for incidence of adverse effects of respiratory failure rates among the 3 comparison groups, results revealed no significant differences. It appeared that corticosteroids in low doses (prednisolone ≤80 mg or hydrocortisone ≤400 mg over 24 hours) are as effective compared to higher doses in the management of severe acute asthma.13
A Cochrane review including 6 RCTs was conducted, where the aim was to investigate the advantages of systemic corticosteroids (oral, IV, IM) vs placebo treatment in patients (adults and children) who were discharged after being treated for acute exacerbation of asthma. Results found that patients treated with corticosteroids had a significantly lower risk of relapse within the first week of discharge, and this risk remained low throughout the first 3 weeks. Those treated with corticosteroids during acute exacerbation also had a significantly less requirement for beta2 agonist to relieve their symptoms and they had a lower risk for following hospital admissions.17
3.3 Chronic Asthma, Step 1- MDI Salbutamol (inhaled short-acting beta2 agonist)
According to the SIGN 101 British Guideline on the Management of Asthma, the management of chronic asthma includes 5 steps. Step 1 is where inhaled short-acting beta2 agonist is used when required. 1 Patient was on MDI salbutamol 2 puffs when required.
A Cochrane review was conducted, with the aim of determining the benefits of treatment of asthma with inhaled short-acting beta2 agonist either on a regular basis or only for relief of symptoms. Results found that there was no statistical difference between the two methods for reduction in airway obstruction as well as the risk of an asthma exacerbation occurring. It was also revealed that those who were treated regularly had a lesser symptoms associated with asthma.19
3.4 Chronic Asthma, Step 2 - MDI Beclometasone dipropionate (inhaled regular standard-dose corticosteroid)
According to the SIGN 101 British Guideline on the Management of Asthma, the second step is where an inhaled steroid 200-800 µg/day is added. 1 The dose of the inhaled steroid was a regular-standard dose. 6 Patient was on MDI beclometasone dipropionate (100 µg) 2 puffs twice a day.
A Cochrane review comparing inhaled beclometasone formulated either with hydrofluoroalkane-134a (HFA) or chlorofluorocarbon (CFC) propellant with placebo for management chronic asthma, included 60 studies and 6542 participants. Results showed that there were significant improvements in FEV1 and morning PEFR, p<0.05, as well as a decrease in use of beta2-agonist for relief in patients not treated with oral steroids and using CFC-beclometasone as compared to placebo. Results also showed that there were significant improvements in FEV1, both morning as well as evening PEFR, and significant reductions in recurrent episodes of symptoms of asthma and daily use of beta2-agonist in patients not treated with oral steroids and using HFA-beclometasone as compared to placebo. These effects were noticeable after a treatment period of 6 weeks.8
Another Cochrane review assessing the presence of correlation between dose and response for patients treated with beclometasone, showed that results from 2 trials indicated only a small improvement advantage in morning PEFR, results from 1 trial indicated only a small improvement advantage in FEV1, and results from another 1 trial indicated minimal decrease advantage in night-time symptoms when patient was on beclometasone 800 µg/day as compared to 400 µg/day. These results were compared to baseline.9
3.5 Chronic Asthma, Step 3 - Inhaled long-acting beta2 agonist + inhaled regular standard-dose corticosteroid
According to the SIGN 101 British Guideline on the Management of Asthma, the third step for management of chronic asthma is where an inhaled long-acting beta2 agonist is added. 1 As the patient is currently on Step 2, she should only move up to Step 3 if improvement of control of her chronic asthma is needed. If she is moved up to Step 3, she would have to continue using her MDI beclometasone dipropionate (100 µg) 2 puffs twice a day with the addition of an MDI long-acting beta2 agonist.
A Cochrane review comparing the efficacy and clinical safety of the addition of inhaled long-acting beta2 agonist to inhaled corticosteroid with inhaled corticosteroid alone for chronic asthma in children and adults, showed that the addition of inhaled long-acting beta2 agonist caused a significant improvement in FEV1, p<0.05, a reduction by 19% in exacerbation risk needing steroids administered systemically, a decrease in usage of short-acting beta2 agonist for relief of symptoms, a decrease in withdrawals and an elevation in proportion of days which are free of symptom. Between the two groups, the risk of adverse effects or withdrawals as a result of adverse effect was not significant.10
A Cochrane review was conducted, to investigate the risk of adverse events in patients with salmeterol (long-acting beta2 agonist) plus inhaled corticosteroids and corticosteroids alone. The corticosteroids in both cases were the same. 30 RCTs were included and it was found that there was no statistical difference between the occurrence of deaths in the combination group and the corticosteroids alone group. As for adverse effects which were not death related, it was also found that there was no statistical difference between both groups.18
In conclusion, the treatment of the patient with severe acute exacerbation of asthma was suitable and supported, based on SIGN 101 British Guideline on the Management of Asthma as well as many reviews and meta-analysis done. She was treated acutely with nebulized salbutamol and ipratropium bromide at the correct doses, according to the SIGN guideline, and evidence have shown that nebulized salbutamol and ipratropium bromide significantly increased pulmonary function and reduced hospital admission rates. She was also treated acutely with IV hydrocortisone which was subsequently replaced with oral prednisolone, both doses were correct, according to the SIGN guideline, and evidence have shown that the use of these corticosteroids in acute treatment were significantly effective in improving pulmonary function, reducing hospitalization, reducing relapses, and reducing need for short-acting beta2 agonist for symptom relief.
She was also treated with MDI salbutamol when required for her chonic asthma, of which was also according to the SIGN guideline. She was also on MDI beclometasone dipropionate, which indicates she was on step 2 on for her management of chronic asthma. Evidence have shown that beclometasone dipropionate significantly improved PEFR as well as morning FEV1, significant reductions in daytime symptoms as well as reduction in need to use short-acting beta2 agonist for symptom relief. Thus, the therapeutic management of the patient is evidence based.