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This case was clerked in Seremban Hospital, Malaysia. The patient is a 67 year old muslim patient. She weighs 62kgs and has a height of 158cm. Her calculated BMI is 24.8 which is normal. She is married for 39 years and has 3 children. On admission to hospital, she complaint of shortness of breath (SOB) for 1 day; fever, lethargy and cough for 3 days; running nose and nausea. She was sent to the hospital's accident and emergency department by her son. She suffered from asthma since childhood. Her past medical history includes hypertension for 10 years and unilateral exophthalmos. She lives with her husband, son and daughter-in-law. She is a housewife. She does not smoke and does not consume alcohol excessively. She has a family history of hypertension as both her parents suffered from hypertension. Before admission, she was on metered dose inhaler (MDI) Salbutamol inhaler when required (PRN), metered dose inhaler Beclomethasone 200mcg twice daily (BD)for asthma and Tablet Amlodipine 10mg once daily (OD) for hypertension.
for step 2 control of asthma.
On examination, she was found to be pyretic with a temperature of 38.3oC. She also had cough with productive sputum, SOB which is not relieved by inhaler and lethargy. Her pulse rate was 100 beats per minute, respiratory rate was 22 breaths per minute and blood pressure was 140/78. She was diagnosed with acute exacerbation of asthma secondary to respiratory tract infection. Several investigations were ordered such as full blood count, renal functions tests and liver function tests. Results of the investigations were as follows:
Full Blood Count appears to be normal EXCEPT
WBC (7.5Â±3.5 x 109/L)
Renal Function Tests appears to be normal EXCEPT
Plasma K (3.4-5.2 mmol/L)
Plasma Creatinine (50-80Âµmol/L)
Creatinine clearance = (140 - age) x weight (kg) x 1.04 (if female) x 1.23 (if male)
= (140 - 67) x 62 x 1.04
A creatinine clearance of 46.76ml/min indicates moderate renal impairment.
Liver Function Test appears to be normal
On day 1, she was pyretic with a temperature of 38.3oc, coughing with production of yellowish sputum, lethargic and had poor appetite and shortness of breath. Her blood pressure, pulse rate and respiratory rate were as above. The doctor plan to start her on a course of Prednisolone 40mg once daily (OD) for five days, Combivent nebulizer immediately then every 4 hourly and Paracetamol 1g immediately then every 6 hourly. She was continued on the medications she was taking previously which were metered dose inhaler (MDI) Salbutamol inhaler when required (PRN), metered dose inhaler Beclomethasone 200mcg twice daily (BD) and Tablet Amlodipine 10mg once daily (OD). Besides that, the doctor also ordered for antibiotic therapy to be started with Azithromycin 500mg OD for five days and Augmentin 625mg BD for 7 days. The doctor also asked the patient to administer eye medication by herself.
On day 2, patient was conscious and talking in full sentences, her SOB improved but the coughing persisted. She still had decrease in appetite. The pharmacist came by the ward to check the technique of MDI usage and counseled the patient on the correct use of the MDI. She was still pyretic with a temperature of 39oc. Her blood pressure was 140/80. Pulse rate was 100 beats per minute and spO2 was 98%. Medicines that were given were continued. The doctor also prescribed bisolvon (bromhexine) for her cough. A potassium supplement, KCl 1.5g OD was also given for hypokalaemia. The doctor also ordered spO2 monitoring to ensure that the levels do not fall below 95%.
On day 3, patient was conscious and alert. She was able to eat slightly and there was no SOB or nausea and vomiting. However, she still had cough. Her blood pressure was 130/70, temperature has gone down to 37.5oc, spO2 was 97% and pulse rate was 98 beats per minute. The plan for the day was to continue oral antibiotics and monitor temperature. Potassium supplement was stopped.
On day 4, the patient was feeling much better. She was only having cough. Her temperature, spO2, blood pressure and respiratory rate were normal. The doctor allowed discharge with azithromycin 500mg OD for a day, augmentin 625mg BD for 3 more days, amlodipine 10mg BD, MDI beclomethasone 200mcg BD and MDI salbutamol when required.
Summary of patient medication:
Drug & Route
Dose & Frequency
CCB for hypertension
Stat then 4 hourly
40mg OD (5/7)
Corticosteroid for asthma
Corticosteroid for asthma
2 puffs PRN
Bronchodilator for asthma
Bronchodilator for asthma
1g stat and every 6 hourly
Non opioid analgesic for fever
500mg OD (5/7)
Macrolide for infection
625mg BD (1/52)
The World Health Organization defines asthma as a long term condition which causes recurrent attack of wheezing and breathlessness which frequency and severity varies among individuals. Asthma is caused by airway inflammation which leads to obstruction that is most likely reversible. The inflammation of airways is due to increased hyperresponsiveness of the airways caused by bacterial or viral infections or allergens which lead to bronchospasm, increased secretion of mucus and oedema.1 In the UK, more than 5 million people are diagnosed with asthma and more than 8 million people have once been diagnosed with asthma.2,3 In year 2006-2007, there were 80,593 cases of asthma attacks that require hospital admissions. 4
Narrowing of the airways in asthma can be caused by overresponsiveness of the immune system to certain substances. In respond to these foreign substances, the immune system produces Ig E antibodies which are specific to the allergen. These antibodies then bind to mast cells. In the early phase response, the antibody and mast cell complex binds to the allergen triggering the release of inflammatory mediators like histamine and eicosanoids on the second encounter of the allergen. Histamine and eicosanoids cause excessive mucus secretion and bronchial wall oedema which leads to airway obstruction. The symptoms appearing at this stage might not be severe, for example, watery eyes and runny nose. In the late phase response, eosinophils infiltration stimulates the release of more inflammatory mediators by release of oxygen derived free radicals and basic proteins.5 The inflammation of the airways worsen as bronchoconstriction occur as a result of hypersensitivity in airway smooth muscles causing worsening symptoms like wheezing, coughing, chest tightness and SOB.6 The pathophysiology of asthma is further proven by features like goblet cell desquamation of epithelial cell, mucus plugs, oedema in mucosa, smooth muscle hypertrophy, infiltration of airways by eosinophils and mast cells, and submucous gland hyperplasia in patients who died from asthma.7
Many allergens can trigger asthma attacks and set off the immune system cascade. This include bacterial and viral infections in the respiratory tract, dust from environment, cigarette smoke, pollens, waste and fur of pets, insects such as cockroaches, mold, drugs such as penicillin, and other chemical substances. Stress, exercise and cold weather may increase chances of asthma attacks. The diagnosis of asthma is made depending on symptoms, hearing a widespread wheeze on auscilation, family history of asthma, low forced expiratory volume in 1 second, FEV1/ peak expiratory flow rate, PEFR and peripheral blood eosinophilia.8 Symptoms of asthma include breathlessness, wheezing, coughing and chest tightness which worsens early morning and at night, when exercising, exposed to cold air or allergens, after taking certain drugs like aspirin or beta blockers.8 Spirometry measurement is widely used and highly effective in determining the degree of airflow obstruction. The best of 3 FEV1 readings and 3 forced expiratory blows after a maximum pause of 2 seconds should be used to determine airflow obstruction.9 Eosinophil count and exhaled nitric oxide concentration (FENO) is also used to measure inflammation of the airways as studies show that in 70-80% of patients with untreated asthma, there is a raised sputum eosinophil count or raised FENO.10 Diagnosis of acute exacerbation of asthma should be based on FEV1 reading, respiratory rate, heart rate and clinical signs such as inability to complete sentence in a breath, hypotension, cyanosis and arrhythmia.
The management of asthma is based on a stepwise approach. According to the SIGN guidelines and British Thoracic Society (BTS), the severity of asthma can be classified into 5 steps, each with a different management plan. In step 1, patient is controlled with a short-acting bronchodilator such as inhaled short-acting Î²2 agonist (salbutamol), inhaled ipratropium bromide which is an antimuscarinic bronchodilator or theophyllines.8 Short-acting Î²2 agonist works by Î²2 adrenoceptor stimulation in the respiratory airways thereby causing bronchial smooth muscle relaxation and mast cell stabilization.11 The effect of a short acting Î²2 agonist only last up to 3 or 4 hours and can produce side effects such as muscle cramps, tremor and nervous tension. Step 2 asthma is managed by addition of a regular preventor therapy such as an inhaled corticosteroid (beclomethasone).8 Inhaled corticosteroids are anti-inflammatory agents acting by inhibiting cytokines production which will cause a reduction in epithelium mediator cells, decrease vascular permeability and eosinophil infiltration, and cause inhibition of eosinophil and macrophage action. There is a risk of candidiasis with corticosteroids, therefore patient is advised to rinse mouth thoroughly after usage.
In step 3 asthma, a long-acting Î²2 agonist such as salmeterol is added8 which has the same mechanism of action as short-acting Î²2 agonists with longer duration of action, for at least 12 hours11 but a longer onset of action. Step 4 asthma is managed by increasing dose of inhaled corticosteroid, adding leukotriene receptor antagonists, adding theophyllines or using slow release Î²2 agonist tablets.8 Theophylline is a bronchodilator which acts by increasing histone deacetylases HDAC to reduce transcription of inflammatory mediators by inhibiting acetylation of histones.12 It also inhibits phosphodiesterase and antagonise adenosine receptor which contributes to the side effects like nausea and vomiting, headache and tachycardia. In step 5 management, patient is controlled with a low dose oral corticosteroid.8 Acute exacerbation of asthma can be managed by the use of high-dose inhaled Î²2 agonist, a combination of ipratropium bromide and Î²2 agonist and oral steroids such as prednisolone.
According to the classification guidelines given by the BTS and SIGN guidelines, the patient is currently suffering from moderate acute asthma based on clinical signs and symptoms, respiratory rate, pulse rate and arterial oxygen saturation. Combivent nebulizer (combination of ipratropium bromide 500mcg and salbutamol 2.5mg/2.5ml) is used in this patient. From randomized trials and 2 meta-analyses comparing patients receiving combination of ipratropium bromide and Î²2 agonist to patients receiving Î²2 agonist therapy by itself in AEBA showed improvement in FEV1 and PEFR.13,14 Another evidence showed that a double blinded, randomized study was performed in patients presenting with acute asthma. The study evaluates the effect of a single dose of combivent compared to a single dose of salbutamol. The results of this study show that the mean absolute difference in FEV1 between combivent and salbutamol alone was 113ml (p < 0.005).15 Therefore, combivent shows clinically significant additional bronchodilator effect compared to treatment using only salbutamol. In a meta-analysis of 10 studies, the addition of ipratropium bromide shows significant improvement in lung fuction and also a decrease rate of admission to hospitals for AEBA in adults.16 In another double-blind, randomized trial, there was significantly greater improvement in FEV1 and increase duration of response with addition of ipratropium bromide to salbutamol compared to salbutamol alone in patients with moderate to severe acute asthma.17 In another study of ipratropium bromide given to patients who are not responding adequately to salbutamol shows that salbutamol has bronchodilator effect by itself, the addition of ipratropium bromide has additional effect especially in patient with severe airflow obstruction.18 From all the evidence given above, the usage of Combivent nebulizer in treatment of this patient is reasonable.
The doctor also managed the acute exacerbation of asthma in this patient using Prednisolone 40mg for 5 days. Prednisolone is a corticosteroid that is indicated in the guidelines as part of the management of acute asthma. In a meta-analysis to determine the use of steroids in acute asthma showed that there is improvement in pulmonary function, decreased in relapse rate and a reduced admission to hospital. Therefore, steroid therapy is beneficial to patients with AEBA.19 A study of 100 patients with moderate or severe acute asthma was carried out using oral prednisolone as the corticosteroid treatment.20 The results show a significant (p<0.001) increase in the FEV1 and PEFR. Another study also showed that oral prednisolone is as effective (if patient is able to tolerate orally) as injected corticosteroids like methylprednisolone or intravenous hydrocortisone.21 Therefore, the use of oral prednisolone in this patient is justified.
The patient was also on Salbutamol 2 puffs when required. Salbutamol is a short-acting Î²2 agonist used in the management of chronic asthma. It can also be used to treat acute asthma. In this patient, salbutamol was given in combination with ipratropium bromide (Combivent) as a nebulizer in addition to the MDI salbutamol.
The patient was also continued on 200mcg beclomethasone BD that she was previously on. Beclomethasone is an inhaled steroid that is used to control patients on step 2 asthma. A study on the efficacy of beclomethasone was carried out to treat mild to moderate asthma. The results show no significant improvement in FEV1 in patients receiving salbutamol and beclomethasone compared to patients receiving only salbutamol. However, results showed that treatment with beclomethasone and salbutamol reduced the admission rate compared to salbutamol alone.22 A double-blind, randomized study was carried out by treating 93 chronic asthma patients with no history of corticosteroid use with beclomethasone.23 The results showed that beclomethasone aerosol increased FEV1 and FVC. In mild to moderate asthma, dose of inhaled corticosteroids used should match the severity of the disease, and use of high dose inhaled steroids and reducing it after that has no additional benefit.24 Inhaled steroids are more effective when given as twice daily dosing than once daily.25 However, little benefit is found for more frequent dosing.25 Therefore, the use, dosage and frequency of dosing used is appropriate.