Asthma as a Chronic Inflammatory Respiratory Disease - Essay Example

of the of the Health sciences and medicine 26 May Asthma Table of Contents 0 Introduction 1 Epidemiology and prevalence Table of Contents 1 Asthma 1.0 Introduction Asthma is a chronic inflammatory respiratory disease which is a considerable drain on healthcare resources in terms of costs, manpower, morbidity and mortality (Akinbami, Moorman & Liu, 2011). It affects adults as well as children and is a global health problem (Australian Centre for Asthma Monitoring 2011). It frequently has associations with COPD, allergies, rhinitis and other respiratory diseases. So far as definition is concerned, there is no gold standard definition. However, asthma can be defined by presence of certain features. Presence of respiratory symptoms (wheeze, bronchoconstriction, breathlessness, cough, chest tightness etc.), chronicity, episodic nature, an inflammatory component and airflow obstruction which is at least partially reversible with treatment are some of these features (SIGN 2012, p. 4). Recent guidelines have strongly emphasised on the inflammatory nature of the disease (Lougheed et al 2012, GINA 2011). Treatment involves management of the chronic disease as well as acute exacerbations, with subtle differences in the management of adult and paediatric patients. 1.1 Epidemiology and prevalence Prevalence of asthma is higher in the developed nations like USA, UK, Australia and north-west Europe but it is increasing in Asia and Africa (Global initiative for asthma, GINA 2011). The trend in UK is increasing from 10% in 1960s to more than 20% in early 2000s (Anderson et al 2007). Nearly 2 million people in Australia suffer from asthma (Australian Centre for Asthma Monitoring 2011). Before puberty, asthma is more prevalent in boys but the trend reverses after puberty. Prevalence is higher in urban areas and metropolitan cities. Socioeconomic status also has an effect with higher prevalence in poor and malnourished individuals. Highest life-time prevalence has been found among school aged children (Simpson & Sheikh 2010). One important trend so far as treatment is concerned has been greater use of inhaled corticosteroids for prevention which has led to decreased mortality and hospital admission rates, while the prevalence has remained constant or increased(Anderson et al 2007). 2.0 Pathophysiology 2.1 Basic pathology behind asthma Asthma is characterized by hyperreactive airways associated with partially or completely reversible airway obstruction. There is chronic and recurrent inflammation of the airways. Airway obstruction mainly results because of the narrowing of the airways caused by smooth muscle contraction in response to various stimuli. Additional obstruction occurs because of plugging of airways with mucous plugs (GINA 2012; NHLBI 2007, p. 16). Because the airways are hyperreactive, a large number of otherwise normal stimuli start instigating a cycle of inflammatory cells activation. These can be common environmental allergens such as pollens, dust, smoke, exhaust fumes & other irritants, respiratory infection, cold, exercise and certain drugs. When any of these stimuli are encountered by the susceptible airways, recruitment of inflammatory cells primarily mast cells, macrophages and eosinophils occur. As an immediate reaction, mast cells with IgE release inflammatory mediators (leukotrienes and cytokines) which are responsible for bringing about smooth muscle contraction, mucosal edema and mucous formation, all of which compromise lumen of the airways. Sequentially, other lymphocytes are recruited escalating the chain of sequences leading to bronchospasm and other clinical manifestations (Mitchell et al 2006, p. 382). 2.2 Role of hypersensitivity and immune system There is a role of immune response in producing and regulating inflammation in asthma. There occurs an imbalance between T1 and T2 helper cells. ‘Hygiene hypothesis’ links asthma to a persistence of T2 helper cytokine pattern that was present in the new born, which later on leads to production of IgE antibody in response to environmental antigens (NHLBI 2007, p. 20). Atopy is the strongest marker for asthma. Patients with atopy have a blown up immune response (immediate hypersensitivity) against routine environmental antigens (Porter et al 2011). A common feature of all these antigens is proteinase activity (Porter et al 2011). The molecular basis by which these proteinases exert inflammatory actions is yet to be deciphered. 2.3 Role of IgE antibody Disease may be classified in to allergic and nonallergic asthma depending upon the presence or absence of environmental allergen reactive IgE antibodies (Murphy & O’Byrne 2010). There are large numbers of high affinity IgE receptors on mast cells (NHLBI 2007, p. 19). These interact with the antigens causing the release of various inflammatory mediators from mast cells which result in bronchoconstriction; and initiating airway inflammation (NHLBI 2007). IgE is the antibody important for allergic reaction and development of inflammation. Infact, monoclonal antibodies that have been developed against IgE have shown promising results in treatment. This reveals the importance of the role that they play in the pathogenesis of the disease (NHLBI 2007, p. 19). 2.4 Role of mediators in bronchoconstriction In an asthmatic inflammatory response, several key mediators are released by the effector cells. Mast cell activation, IgE dependant or independent is the critical step. TNF-? is released which promotes migration of neutrophils and dendritic cells. Basophils are required for differentiation of T2 helper cells and also release interleukin (IL) 4 & 6. Role played by eosinophils in the pathogenesis of asthma is not clear. However, therapy against IL 5, which promotes eosinophil survival, has been shown to reduce exacerbations and medication. Chemoattractant IL 8 is responsible for an increased number of neutrophils in the airways (Murphy & O’Byrne 2010). Leukotrienes are produced by mast cells and eosinophils and are potent bronchoconstrictors. Only pro-inflammatory mediators whose inhibition leads to an improvement in the lung function are leukotrienes. Other than cytokines and leukotrienes, histamine, nitric oxide and prostaglandins also contribute to the inflammatory response (GINA 2011). 2.5 Outcomes The end result of allergen exposure, anaphylactoid type reaction, IgE antibody and mast cell activation is airway inflammation and remodelling. Airway remodelling involves subepithelial fibrosis, hyperplasia and hypertrophy of smooth muscles, angiogenesis and mucous hypersecretion (GINA 2012). 3.0 Risk Factors 3.1 Genetic predisposition Genetic basis of the disease has been suggested by family and twin studies. Causation of asthma has been now recognised as multifactorial. No single gene can point towards all the variations in asthma seen in the population. Gene-gene interaction and gene-environment interaction lead to manifestation of the disease. Four groups of genes have been determined to be susceptible for asthma. These are the genes involved in 1) skin and mucosal defense, 2) recognition and presentation of the antigen 3) immunoregulation, and 4) T2 helper cells differentiation (Barnes 2011). Various single nucleotide polymorphisms (SNPs) and candidate genes have been studied and indentified as being found in association with asthmatic individuals (Meng & Rosenwasser 2010). Chromosome regions which determine susceptibility to asthma such as locus on chromosome 5 which is associated with serum IgE production have been recognised. However, whether they conclusively cause asthma and how they are related to the phenotypic expression of the disease are yet to be answered questions. 3.2 Stress induced asthma Stresses such as cold and exercise have been known to provoke bronchospasm in patients with hyperreactive airways (Hilberg 2007). Exercise induced symptoms start after the exercise but rarely during exercise (GINA 2010). Respiratory infections with bacterial and viral agents as well as weather changes also act as stressors or triggers for asthma. Also, there is a tendency for exacerbations to occur at night. This phenomenon is called nocturnal asthma (GINA 2012). Exposure to tobacco smoke and environmental pollutants are also risk factors for the development of asthma. 3.3 Use of drugs Many drugs can produce bronchospasm in normal individuals and provoke an asthmatic attack in a patient. Most important among these are aspirin and other non-steroidal anti-inflammatory drugs, beta blockers including timolol eye drops, interleukin-2, vinca alkaloids and nitrofurantoin (Ozkan, Dweik & Ahmad 2001). Aspirin induced asthma manifests as bronchoconstriction, nasal congestion, rhinorrhoea and flushing of skin half to three hours after ingestion of aspirin. It’s an anaphylactoid type of reaction. Its prevalence in Australia is 10.5% and it’s more common in women (Gohil, Modan & Gohil). Age of onset is usually after 30 years (Ozkan, Dweik & Ahmad 2001). Beta blockers should also be avoided in people with known obstructive disease as they can provoke severe bronchospasm in such patients (Ozkan, Dweik & Ahmad 2001). 3.4 Family history of allergy Family history of atopy, especially maternal is a very strong risk factor for onset and persistence of wheeze, atopy and asthma in children (SIGN 2012, p. 6). In all probability, genes related to atopy or airway hyperresponsiveness are inherited and lend a heritable component to asthma (GINA 2012, p. 4). 4.0 Signs & Symptoms 4.1 Symptoms Patients with asthma may variably define their symptoms as recurrent attacks of wheezing, nocturnal cough, exercised induced cough and wheeze, frequent rhinitis and increased severity and frequency of these symptoms on exposure to environmental antigens (GINA 2012). In mild asthma, patient may report breathlessness with change of season, dyspnea on more than routine exertion, recurrent nasal congestion and cough. In acute severe asthma, patients present with tachypnea, tachycardia, extreme air hunger, and inability to speak sentences in one breath (SIGN 2012). 4.2 Signs In mild asthma, signs are usually minimal. Wheezing or noisy breathing may be present normally or during expiratory phase of a forceful breath. Nasal polyps may be present in those with history of allergies. Atopic dermatitis is a frequent correlation in atopic individuals (NHLBI 2007, p. 43). On respiratory system examination, wheeze is the commonest adventitious sound heard. Increased likelihood of asthma is suggested by physical findings of chest hyperexpansion. This finding is more likely in children and may be associated with hunched shoulders and deformity of the chest (NHLBI 2007, p. 42). In life threatening cases, wheeze may be absent because of total airflow obstruction. Other associated signs that may be present are tachycardia, depressed consciousness, cyanosis, difficulty speaking, and other signs of respiratory distress such as use of accessory muscles of respiration, hypotension and arrhythmias (SIGN 2012, p. 60). 5.0 Diagnosis Diagnosis of asthma in an individual requires a history of airway hyperresponsiveness and airway obstruction; and spirometry for establishment of airway obstruction and its reversibility. Airway obstruction should be episodic and its alternative diagnoses should have been excluded. Reversibility is defined as an increase of ? 12 % increase from baseline FEV1 or ? 10% increase in predicted FEV1 post inhalation of a bronchodilator with short duration of action like 2 to 4 puffs of albuterol with 90 mcg in each puff (NHLBI 2007, p. 40). An increase of more than 400 ml in FEV1 strongly suggests asthma (SIGN 2012, p. 19). Spirometry is important in diagnosis of asthma as it is an objective measure of airflow limitation (NHLBI 2007, p. 43). It helps in the exclusion of other lung disorders which sometimes cannot be done on the basis of history alone. In infants and children less than five years, assessment can only be done clinically. Other investigations which may help in diagnosis are peak expiratory flow rate and non invasive measures of inflammation such as sputum eosinophil count and exhaled nitric oxide concentration (SIGN 2012, p. 18; Lougheed et al 2012). 6.0 Management National heart, lung and blood institute (2007) has described four components of asthma management. These are assessment and monitoring of the disease, education about the disease, prevention of environmental exposure and pharmacological therapy (p. 35). 6.1 Acute Exacerbation An acute exacerbation should be managed early (NHLBI 2007). This can be started by the patient as home based intervention. Patients should be educated to recognise the symptoms of an exacerbation and be given a written plan about what to do in case of an acute attack. In the emergency department or the hospital setting, the treatment involves oxygen, bronchodilators and corticosteroids. All hypoxaemic patients of severe asthma should be given supplemental oxygen. The target is to maintain saturation above 95%. In hospitals and ambulances, oxygen should be used for nebulisation of beta agonists. Hypercapnea denotes life threatening attack and needs anaesthetic/airway intervention. Continuous nebulisation may be more effective than bolus nebulisation (SIGN 2012, p. 62). Severe cases may require intravenous magnesium sulphate administration and HELIOX therapy. Intravenous aminophylline has not been found to have any benefit and is associated with many side effects (SIGN 2012, p. 64). Combination of ipratropium bromide, an anticholinergic, with beta2 agonist agents given as nebulisation provides much greater bronchodilation than SABA alone (SIGN 2012, p. 63). Thus, in an acute severe exacerbation, 0.5 mg ipratropium can be used 4 to 6 hourly. Infants are at a greater risk of respiratory failure and should be hospitalised early. Viral infections can lead to wheezing and should be managed without antibiotics (NHLBI 2007, p. 378). 6.1.1 Role of inhalers and nebulizers Inhalation route is preferred for drug administration in acute management as well maintenance therapy of asthma. The drug is delivered at the site of action so that the systemic side effects are reduced. Devices to deliver inhalational agents are metered dose inhalers which are pressurised or breath actuated, dry powder inhalers and nebulisers which deliver drug in the aerosol form (GINA 2012, p. 30). Patients are educated about the coordinate steps needed to deliver the medication. Spacers are sometimes used to improve drug delivery and deposition in the lungs. It is recommended that pressurised metered dose inhalers with spacer should be used to treat mild to moderate exacerbations of asthma in children and adults (SIGN 2012, p. 55). In those who are unable to use them, the choice of other devices should be guided by the choice of the drug. 6.1.2 Role of bronchodilators in mild acute attacks Mild cases of asthma usually get prompt relief with inhaled short acting beta agonists (SABA)( Bacharier 2008). A short course of oral systemic corticosteroids is given when symptoms are not relieved with SABA (NHLBI 2007). A high dose inhaled beta2 agonist agent is the first line therapy for relieving bronchoconstriction in an acute attack of asthma (SIGN 2012). Intravenous beta2 agonists are used only when inhaled therapy is ineffective at relieving symptoms. 6.1.3 Role of corticosteroids in severe acute attacks Severe asthma is characterised by dyspnea at rest and peak expiratory flow rate (PEFR) < 40%. These patients need hospitalisation and oral systemic steroids as SABA provides only partial relief (NHLBI 2007). The earlier the steroids are given in an acute attack, the better it is. They can be administered in tablet as well as injectable form. Oral prednisolone 40-50 mg or intravenous hydrocortisone 100 mg 6 hourly are usually effective at relieving symptoms (SIGN 2012). Inhaled corticosteroids are also started for the chronic management of asthma. 6.1.4 Role of paramedic Paramedics are usually involved in the pre hospital management of an acute asthmatic attack as a part of EMS team. They should be able to elicit the medical and treatment history of the patient, assess the severity of obstruction and identify the life threatening conditions. They inform the ED about the status of the patient on their way to the hospital, provide oxygen, establish IV access if required, administer inhalational and systemic bronchodilators and establish and maintain an artificial airway. They should be aware of the ‘reliever’ medications (GINA 2012) which act quickly to relieve bronchoconstriction such as SABA, inhalational anticholinergics, theophylline and oral short acting beta 2 agonists. Current updates recommend standing orders for albuterol, ipratropium and oral corticosteroids for prehospital management (NHLBI 2007, p. 374). 6.2 Chronic Asthma Patient education is also important in the management of chronic stable asthma for symptom control and prevention of acute exacerbations. They should be taught to avoid the triggering agents and the medications which may provoke bronchospasm. Support and encouragement should be provided to quit smoking. Drug delivery device use should be taught and periodically reviewed. Peak expiratory flow rate is a good agent for monitoring of diagnosed asthma. The importance of inhaled corticosteroids in the prevention of an acute attack should be emphasised. ‘Controller’ drugs are used in the management of chronic asthma. These include corticosteroids, long acting beta2 agonists, leukotriene modifiers and antibodies against IgE (GINA 2012, p.30). The goals of treatment are to achieve control of symptoms and prevent side effects of medications. There should be no night awakenings, acute exacerbations and improvement in exercise tolerance (SIGN 2012). It has been found that for achieving these goals, inhalational corticosteroids are the most effective agents in adults and children more than 5 years. Various studies have shown their efficacy in improving lung function and reducing mortality (GINA 2012). Most of the drugs are effective in doses equivalent to 400 microgram budesonide per day (BDP) (GINA 2012). Other examples are beclomethasone dipropionate, fluticasone and triamcinolone. In case of inadequate relief with inhaled corticosteroids, add on therapy is recommended over increasing the dose. 6.2.1 Role of corticosteroids combined with bronchodilators In children less than 5 years of age who are using beta-2 agonists more than 3 times a week, consideration should be given to combining inhaled corticosteroids with bronchodilators (SIGN 2012). Most of the corticosteroids are maximally effective at twice daily dosing. However, the long term effects of topical corticosteroid therapy like this are to be explained to the patients. In adults, these may range from oral candidiasis to bone loss. In children, growth failure and adrenal suppression may occur. Mouth washing after taking the drug decreases the incidence of oral fungal infection. Leukotriene receptor antagonists are good alternative to inhaled corticosteroids in children less than 5 years who are unable to take those (SIGN 2012). 7.0 Summary To conclude, asthma is a chronic disease with serious health and financial repercussions. It is clinically characterised by partially reversible airway obstruction with an underlying basis of inflammation. Genetic factors, family history and drugs are the main risk factors. Treatment involves patient education, relief of symptoms by bronchodilators and corticosteroids and maintenance therapy for chronic asthma with inhalational corticosteroids. Paramedics are involved in the first aid management of an acute disease and transportation of the patient to the hospital. Thus, it is crucial for them to be able to diagnose, assess and administer the treatment which may be life saving in patients with an acute severe attack. Reference list Akinbami, LJ, Moorman, JE & Liu, X 2011, Asthma Prevalence, Health Care Use, and Mortality: United States, 2005–2009 (National Health Statistics Report No.32), National Centre for Health Statistics, Hyattsville, MD. Anderson, HR,Gupta, R, Strachan, DP & Limb, ES 2007, ‘50 years of asthma: UK trends from 1955 to 2004’, Thorax, vol. 62, pp.85–90. Australian Centre for Asthma Monitoring 2011, Asthma in Australia 2011. AIHW Asthma Series no. 4, Cat. no. ACM 22, AIHW, Canberra. Bacharier, LB, Boner, A, Carlsen, K, Eigenmann, PA, Frischer, T, Gctz, M et al. 2008, ‘Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report’, Allergy, vol. 63, pp. 5–34. Barnes, KC 2011, ‘Genetic studies of etiology of asthma’, Proceedings of American Thoracic Society, vol. 8, pp. 143-148. Global Initiative for Asthma (GINA) 2011, Global strategy for asthma management and prevention 2011 update, Global Initiative for Asthma (GINA), viewed 25 May 2012, Gohil, U, Modan, A & Gohil, P 2010, ‘Aspirin induced asthma- a review’, Global Journal of Pharmacology, vol. 4, no. 1, pp. 19-30. Hilberg, T 2007, ‘Etiology of exercise-induced asthma: physical stress-induced transcription’, Current Allergy Asthma Rep, vol. 7, no.1, pp. 27-32. Lougheed, MD, Lemiere, C, Ducharme,FM, Licskai, C, Dell, SD, Rowe, BH, FitzGerald, M, Leigh, R, Watson & W, Boulet, L 2012, ‘Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults’, Canadian Respiratory Journal, vol.19, no. 2, pp. 127-164. Meng, J & Rosenwasser, LJ 2010, ‘Unraveling the genetic Basis of asthma and allergic diseases’, Allergy Asthma and Immunology Research, vol. 2, no. 4, pp. 215-227. Mitchell, NR, Kumar, V, Abbas, AK & Fausto, N 2006, Pocket companion to Robbins and Cotran pathologic basis of disease (7th ed.), Saunders, Philadelphia. Murphy, DM & O'Byrne, PM 2010, ‘Recent advances in the pathophysiology of asthma’, Chest, vol.137, pp. 1417-1426. National Heart, Lung, and Blood Institute (NHLBI) 2007, National Asthma Education Prevention Program (NAEPP). Expert Panel Report 3: Guidelines for the diagnosis and management of Asthma, National Heart, Lung, and Blood Institute, Bethesda, viewed 25 May 2012, Ozkan, M, Dweik, RA & Ahmad, M 2001, ‘Drug-induced lung disease’, Cleveland Clinic Journal of Medicine, vol. 68, no. 9, pp. 782-795. Porter, PC, Ongeri, V, Luong, A, Kheradmand, F & Corry, DB 2011, ‘Seeking common pathophysiology in asthma, atopy and sinusitis’, Trends in Immunology, vol. 32, no. 2, pp. 43-49. Scottish Intercollegiate Guidelines Network (SIGN); British Thoracic Society 2012, British Guideline on the Management of Asthma: a national clinical guideline, Scottish Intercollegiate Guidelines Network (SIGN), Scotland, viewed 25 May 2012, Simpson, CR & Sheikh, A 2010, ‘Trends in the epidemiology of asthma in England: a national study of 333,294 patients’, Journal of Royal Society of Medicine, vol. 103, pp. 98–106. Read More