Asthma as a Chronic Inflammation - Essay Example

Introduction: Asthma is a chronic inflammation of airways characterized by continuous and developing inflammatory process that later produces variable clinical presentation such as cough, wheezing etc. Acute inflammation results in broncho-spasm while chronic inflammation affects airway caliber and airflow, thus causing bronchial hyper-responsiveness. Asthma influences the overall health status of individuals. Reportedly, patients experience worse self-assessed health, reduced physical functionality, sleep disturbances, low social and daily activities etc. Patients exhibit a tendency to go into depression (ACAM, 2008). 2. Historical Background of Asthma: Asthma originates from Greek word meaning "Shortness of breath". Later in 19th century, asthma was defined by Dr. Salter as the disease in which smooth muscles of airway contract resulting in constricted airways. Later, Dr. Osler the father of modern medicine described the inflammatory process, excessive smooth muscle constriction and hyper mucosal secretion that defined the basis for pharmacological management. In 1970's and 80's clinical trials and evidence suggested the basis for airway remodeling due to persistent exacerbations and allergen or irritant stimuli in the instigation of allergic asthma. These discoveries led to better understanding of patho-physiology of disease and later drug therapy (Holgate, 2010) 3. Epidemiology: 3.1. Prevalence: Recent research suggests that asthma affects 5% of the total population (Porth, 2010) with the incidence rate of 15 million in U.S (Sherwood, 2012). In Australia, an estimated 2.2 million population suffers from asthma with incidence rate of 14-16% and 10-12% in children and adults respectively (NAC, 2006). According to Brenner (2007), it is one of the most common chronic childhood disease affecting about 5-6 million children annually. This makes it the fourth leading cause of disability in U.S. It accounts for 1.5-2 million emergency department visits per year (Brenner, 1999). The prevalence of asthma is reportedly higher in socio-economically disadvantaged background. Studies indicate the risk of asthma development in children is related to lower socio-economic status and poverty (ACAM, 2008). 3.2 Mortality and Morbidity: Although occurrence of asthma is reportedly doubled in past several years however, the morbidity and mortality rates have dramatically decreased due to successful management with patient education, self-monitoring, combination drug therapy and asthma action plan (Porth, 2010). Overall, a sharp decline in mortality rate (69%) is witnessed in the past twenty years. In Australia, 0.30% of the mortality is attributed to asthma alone. Risk factor of death from asthma increases with age. Majority of deaths caused by asthma are attributed to respiratory infections (ACAM, 2008). Other risk factors for mortality due to asthma include severe exacerbation, more than two recent hospitalization episodes, lower socio-economic status, and failure to perceive and implement asthma action plan, illicit drug use, psychiatric issues, chronic lung and cardiovascular diseases (NAEPP, 2007). 4. Etiology: The common factor responsible for all types of asthma is hyper-responsiveness to certain stimuli. Research suggests that the occurrence of inflammatory cells (eosinophils, mast cella tc) contribute to pathogenesis of disease (Porth, 2010). Risk factors for the development of asthma include history of atopy (genetic tendency to develop IgE), viral respiratory infections, gene-environment interaction etc. A number of patients experience constant variations in airway structure like fibrosis, mucous hyper-secretion and smooth muscle hypertrophy may attribute to asthma development (NAEPP, 2007). There is strong relation between asthma and allergy. Evidence suggests that more than 80% people suffering from asthma have allergic disorders such as eczema, allergic rhinitis etc. 5. Pathophysiology: 5.1 Physiology of respiratory system: Respiratory process is a complex and intricate process that is mainly involves lungs, trachea, bronchi, alveoli and smooth muscles. Air flows in the lungs through trachea and bronchi that is supported by cartilaginous muscles. This airflow works on air pressure principle that it flows from high pressure gradient to low pressure gradient. Lungs maintain a low pressure gradient thus causing the air to flow in (Sherwood, 2012). From upper respiratory tract it moves to lower pulmonary airways i.e. bronchi and alveoli. Bronchi and alveoli are located in the lungs and are surrounded by criss-cross smooth muscle innervated by autonomic nerves. The involuntary contraction and relaxation of these smooth muscles regulates the bronchi airway diameter. When the body is in resting position bronchi constrict thus limiting airflow. Likewise, during the exercise, bronchi relax allowing increase in airflow. Bronchial smooth muscles respond to inflammatory factors that cause airway constriction such as histamine (Porth, 2010). 5.2 Asthma mechanism: Patients with asthma experience airway constriction which is a direct consequence of swelling, inflammation and narrowing of smooth muscles. This process is aggravated by smooth muscle hypertrophy and hyperplasia, intrusion of inflammatory cells, edema, over-secretion of mucous, protein deposition specifically collagen, epithelial lining desquamation. Thus delayed management or treatment can lead to long term alterations in airway passages including increased blood flow to bronchial region, collagen thickening and loss of airway dispensability (NAC, 2006). According to NAEPP (2007), airway variation and airflow obstruction are caused by a wide number of factors in asthma. These include: 1. In response to allergens or irritants, bronchial smooth muscles constrict causing broncho-constriction. As a consequence limited airflow, broncho-spasm is experienced. 2. The progression of inflammation and persistent symptoms results in airway edema, mucous over-secretion, mucous plug formation. Structural changes in smooth muscles such as hyperplasia and hypertrophy may accompany as the inflammatory process becomes chronic. 3. Airway hyper-responsiveness contributes limited airflow due to broncho-constriction. a. Inflammation of airways: Basically, asthma is the chronic inflammation of airways in which epithelial lining and many cells play a vital role specifically mast cells, eosinophils, lymphocytes, macrophages, neutrophils etc. The inflammation of airways causes symptoms such as cough, breathlessness, persistent wheezing, chest tightness etc. along with variable airflow obstruction that is reversed either with or without treatment. An increase in existing bronchial hyper-responsiveness to multiple stimuli is also associated with the inflammation (NAC, 2006). The immune-histopathological basis of asthma is inflammatory cell infiltration. Neutrophils, eosinophils, lymphocytes initiate the process; while mast cells activation and epithelial cell injury follows in. The inflammatory process thus instigates airway hyper-responsiveness, limited airflow, respiratory symptoms and disease severity (NAEPP, 2007). Also, the development of disease process is instigated by inflammation. Inflammatory process involves interaction of several inflammatory cells and mediators. Inflammatory cells comprise of lymphocytes typically T1 and T2 helper cells, mast cells that initiate the production of histamine and cytokines, eosinphils, neutrophils, dendritic cells, macrophages, epithelial cells etc. Mediators include chemokines, cytokines, cysteinyl-leukotrienes, nitric oxide, IgE antibodies etc. (Porth, 2010). Asthma pathophysiology can be understood by the flow chart (Figure 1. Pathophysiology of asthma) It is vital to understand and research the role of inflammatory cells and mediators in order to device optimal drug therapy aimed at reducing airway inflammation, broncho-spasm, structural changes in smooth muscles and mucosal hyper-secretion. 5.3. Pathogenesis: Asthma originates as a result of structural and functional airways variations triggered by environmental factors. This variation in airways leads to allergic sensitization and produces variable chronic symptoms. Pathogenesis of disease is mainly dependent on two factors i.e. genetic and environmental exposure. Genetic factors enhance the incidence of asthma of asthma in progeny. Environmental factors include exposure to allergens, pollutants, specific medications and viral respiratory infections. The contribution of genetic and environmental factors varies in different settings which explains the diversity of symptoms from patient to patient. Pathogenesis of asthma follows a characteristic pattern which is associated with complex pathways involving several cell types and mediators. Cells involved in development of disease include TH2, mast cells, eosinophils, basophils, neutrophils, epithelial cells and natural killer T cells. In response to environmental factors, these cells collaborate and induce airway hyper-responsiveness and later typical asthma symptoms (Umetsu and DeKruyff, 2010). 6. Diagnosis: Diagnosis of asthma is based upon patient history, physical examination and diagnostic tests. 1. History: Patient history is vital in diagnosis of asthma. Medical history of new patient with suspected asthma includes upper respiratory tract infection. Typical symptoms such as wheezing, chest tightness, cough, sputum production etc. suggest of asthma (NAC, 2006). History should evaluate duration and onset of symptoms i.e. seasonal, annual, nocturnal or early morning along with frequency, duration and onset of exacerbation. Family history of atopy, eczema, dermatitis, hay fever etc should also be questioned. Home work environment, social history, life style, and aggravating factors for symptoms like exercise, viral infections, allergens etc (NAEPP, 2007). 2. Physical examination: Physical examination includes chest examination for hyperinflation and wheezing. Signs of allergic rhinitis should also be observed (NAC, 2006). Symptoms that might show on physical examination include hyper-expansion of thoracic region which may be accompanied by chest deformity or use of accessory muscle, wheezing sounds during normal breathing, enhanced nasal secretions, presence of nasal polyps, eczema or atopic dermatitis (NAEEP, 2007). 3. Diagnostic testing: Precise measurement of respiratory function is vital in diagnosis as well as management of asthma. For this purpose several diagnostic tests may be performed but most important of them is spirometry. a. Spirometry: One of the most reliable tests for diagnosis of asthma is spirometry which aids in assessing variation in air flow limitation and comparison of this air flow limitation to that of normal airflow (NAC 2006; NAEEP, 2007). b. Chest X-ray: Usually a chest x ray is not required in diagnosis of asthma however in conditions such as uncertain variable symptoms and the need to rule out other ailments e.g. pneumonia. c. Challenge test: Challenge tests may help in diagnosis of asthma in case of suspected occupational asthma, uncertain diagnosis or if the patient does not respond to asthma treatment. These tests include hypertonic saline, mannitol, histamine and dry air etc (NAC, 2006). d. Allergy test: Allergens are a major cause of asthma and allergy testing is vital in management of asthma. Presently allergy tests that are available include Allergy skin prick tests (SPT) and Radioallergosorbent test (RAST). Both of these are based on detection of allergen specific IgE (NAC, 2006). Clinicians should not only rely on symptoms alone for the diagnosis of asthma as some of conditions are often confused and misdiagnosed with asthma. These include recurrent non-specific cough in association with upper respiratory tract infection, chronic suppurative lung disease (chronic bronchitis and bronchiectasis), exercise induced respiratory dyspnea and laryngeal dysfunction (NAC, 2006). Therefore, NAEPP (2007) recommends additional pulmonary function tests, broncho- provocation and measurement of biomarker inflammation. 7. Classification of Asthma: Disease severity and pattern is vital in initial stages of asthma diagnosis as it helps the physicians to decide the best medication and management practice. Subsequently frequency of medical review and formulation of asthma action plan is also dependent upon asthma classification (GINA, 2011; NAC, 2006). 8. Management of Asthma: 8.1 Pre-hospital management: Patients at risk of high respiratory attacks must start treatment from home. Pre-hospital management includes use of ICS and SABA. If the patient feels relief from symptoms then he/she should discuss the condition with consultant on next appointment. However, if the there is no response to treatment then, patient should be rushed to ER. According to Brenner (1999), pre-hospital management by a paramedic includes assessment of severity of asthma attack, patency of airways, alertness or normal responses to environment/people, breathing and respiratory rate, movement of accessory muscles, breathing sounds i.e. wheezing, discomfort etc and ability to count till 10 without breathlessness. Pharmacological management for such patients includes bronchodilator therapy, oxygenation, and continuous supply of beta-2 agonist with nebulizer or inhaler. Some special considerations must be kept in mind by the emergency medical staff during treatment of acute asthma. These include administration of corticosteroids in prolonged field transportation and assessment of any other disturbing symptoms like fever, vomiting etc. According to NAC (2006), asthma management plan should be based upon six steps i.e. 1. Assessment of asthma severity 2. Treatment focused on achieving best lung function 3. Once accomplished best lung function; should be maintained through identification of stimuli and later avoiding it 4. Optimization of pharmacological treatment. 5. Development and improvisation of written asthma action plan 6. Patient education, regular monitoring and follow up 8.2 Drug Therapy: Focus of pharmacological treatment is to manage symptoms, accomplish and maintain best lung function with lower dosage and least side-effects. According to NAC (2006), best asthma control should deliver minimum symptoms, minimal requirement for medication, no exacerbation, unrestricted physical activity and normal lung function (FEV1 and PEF>80%). According to NAEPP (2007), asthma medications can be divided into long term control aimed at management of persistent and chronic asthma; and quick relief medication that is used to relieve acute symptoms and exacerbations. Long term medications include corticosteroids in the form of ICS, cromolyn sodium, immunomodulators, leukotriene modifiers, LABA (salmeterol and formoterol) and methylxanthines etc. Quick relief medications comprise of anticholinergics, SABA (albuterol, pirbuterol), systemic corticosteroids etc. Studies represent that medication used in asthma control should be delivered through inhalation system as it is better than oral or parenteral mode of delivery. Usually two methods of inhalations are used i.e. Metered-dose inhaler (MDI) and Dry powder inhaler (NAC, 2006). Lately, a gradual increase in the management of asthma through long acting beta-agonist in combination with ICS is reported. This possibly suggests improved level of asthma control. However, studies indicate several age related differences in asthma treatment. Overall, use of medication increases with age i.e. children are prescribed less potent ICS formulation which are only dispensed once a year while among adults ICS is prescribed in combination with long acting beta-agonists (ACAM, 2008). 8.3 Prevention: Avoiding trigger factors: Continuous exposure to factors that trigger asthma might worsen asthma symptoms. Therefore, it is necessary to identify and evaluate trigger factors that elicit asthma. These include: 1. Allergens: Patient history is often helpful in assessing allergens. Confirmation tests should be carried out to confirm allergen (NAEPP, 2007). Commonly known allergens include house dust mite, pollen, animal debris etc. House dust mites should be avoided by ensuring household cleanliness, removal of carpets and decreased humidity. Pollen, fungal spores, trees and grass etc. may trigger asthma symptoms (GINA, 2011). Strong aromas and perfumes may also irritate asthma patients. 2. Respiratory infections: Children may suffer from broncholitis caused due to viral infections such as respiratory syncytial virus (RSV) and parainfluenza virus. Broncholitis ultimately might develop into asthma. Recent studies suggest that in about 50% of the asthma adult patients; underlying cause is Chlamydia pneumoniae, a common lung infection. Asthma patients should be administered influenza vaccine to avoid viral respiratory infection (NAEPP, 2007). 3. Exercise 4. Drugs: some drugs might cause or worsen asthma such as beta-adrenergic blocking agents, aspirin or NSAIDs, cholinesterase inhibitors etc (GINA, 2011). 5. Diet: food allergies are uncommon source; however, sensitivity to some food like milk, egg, shell fish etc might trigger episodes of cough or wheezing. 6. Gastro-esophageal reflux (GORD): Around 40% of adult asthma patients experience GORD. 7. Air pollutants: Indoor or outdoor air pollutants might trigger exacerbations. Commonly known pollutants include smog, fire smoke, all volatile organic compounds (VOCs), tobacco smoke, chemicals, formaldehyde, NO2 (NAC, 2006). 8. Smoking 9. Temperature variation 10. Occupational factors: Occupational asthma is stimulated by gases, fumes, organic and chemical dust etc. 8.4 Patient education: Patient education and awareness of asthma is vital in its management. Understanding of the fact, that this disease is an inflammatory process rather than a bronchospasm helps them comprehend separate types of medication required for disease management i.e. bronchodilator medication referred as reliever, anti-inflammatory medication referred as preventer medication (NAC, 2006). GINA (2011) suggests that patient education regarding asthma control and management include several measures such as: ? Allergen avoidance ? Implementation of written asthma plan ? Smoking cessation ? Exercise and diet management 8.5 Long term asthma management: According to GINA (2011) and NAEPP (2007), the focus of long term asthma management is to: 1. Decrease impairment through prevention of chronic symptom. This requires intermittent use of inhaled short acting beta2 agonist, preservation of normal pulmonary function and maintenance of normal daily activities. 2. Reduce risk factors such as prevention of frequent exacerbations and progressive loss of lung function and in case of children lung growth, less hospitalizations and emergency department visits. 3. Maintaining a step-wise pharmacological approach that induces best achievable results with minimal side effects. 4. Regular monitoring and follow up of patient at 1-6 months interval with emphasis on asthma manifestation and improvement of symptoms through long term medication directed towards suppression of inflammatory process. 5. Patient education regarding prescribed use of pharmacological therapy, allergen, irritants and comorbid conditions avoidance that aggravate asthmatic condition. Individual and well written asthma action plan is vital in daily management of disease. Clinicians should emphasize on comprehension and implementation of action plan that alerts the patient about asthma initiation and relief (NAEPP, 2007) Several co-morbid condition that co-exist with asthma include Allergic broncho-pulmonary aspergillosis (ABPA), gastroesophageal reflux (GORD), chronic stress/depression, obesity, obstructive sleep apnea (OSA), Rhinitis/sinusitis etc. Physicians must evaluate these co-morbid conditions in patiens as in most of the cases, management of these conditions aid in relief from asthma symptoms (NAEPP, 2007). 9. Conclusion: In conclusion asthma is an inflammatory disease of respiratory system. The overall, incidence of asthma is increasing however, with better management practices mortality and morbidity rates are lowered. The complex pathophysiology of this disease involves inflammatory cell and mediators. Management practices should rely on less potent medication, avoidance of allergens and relief of symptoms. Figure 1. Pathophysiology of Asthma. Reproduced from Porth (2010) References: Australian center for asthma control (ACAM), 2008. Asthma in Autralia. Australian institute of Health nd welfare. http://www.nationalasthma.org.au/uploads/publication/asthma-in-australia-2008.pdf Brenner, B. 1999. Emergency Asthma. CRC Press. New York. pp, 505-521. Holgate, S. 2010. A breif history of asthma and its mechanisms to modern concepts of disease pathogenesis. Allergy Asthma Immunol. Res. July 2010; 2(3):165-171. National Asthma Council Australia (NAC). 2006. Asthma management handbook. Sixth edition. Pp. 1-120. "Global Initiative for Asthma (GINA). 2011. A pocket guide for physicians and nurses. http://www.ginasthma.org/Guidelineitem.asp??l1=2&l2=1&intId=1561. GINA 2010 National Asthma Education and Prevention Program (NAEPP) (2007). "Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma" (PDF). National Heart Lung and Blood Institute. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Porth, C. 2010. Essentials of pathophysiology. Lippincott Williams and Wilkins. pp. 570-579. Sherwood, L. 2012. Human physiology: from cells to systems. Cengage learning. 8th edition. U.S.A. pp. 457-469. Umetsu, D. and DeKruyff, R. 2010. Natural Killer T cells are important in pathogenesis of asthma: The many pathways to asthma. The Journal of Allergy and Clinical Immunology. Vol. 125 (5), pp. 975-979. Read More