Essay: Asthma

INTRODUCTION
Asthma is a common chronic respiratory disease with a global prevalence of more than 200 million. It is a heterogeneous disease identified by reversible airflow obstruction, bronchial hyperresponsiveness (BHR) and inflammation. Treatment of inhaled corticosteroids (ICS) and/or combination of long acting ??-agonist (LABA) may deviate in dosage depending on the measure of severity among patients. Asthma can also be classified into two categories; extrinsic (atopic) and intrinsic (non-atopic) asthma (Fahy, 2014). For this case study, I would be discussing some characteristics of asthma, diagnosis and treatment recommendations and current research in stratified medicine.
ETIOLOGY
Atopic asthma is triggered by environmental stimuli such as allergens (e.g. pollen, pet hair, dust mites etc.), air pollution, weather change and childhood exposure to tobacco smoke. Less than 15% of children with continuous wheezing would develop asthma in adolescent while others with eczema, obesity, atopic rhinitis and dermatitis are at higher risk of developing asthma. These comorbidities may complicate asthma management in adulthood (Subbarao, 2009). Furthermore, there is a higher prevalence of asthma among boys than girls, and a higher incidence among women than men, due to hormonal factors. Boys generally undergo asthma remission as a result of enhanced lung development and airway growth (Spahn, 2008) whereas hormonal influences could affect asthma control in pregnancy (Padmanabhan, 2014).
Other risk factors which could affect the immune system in new-onset asthma are exercise, emotional stress and occupational exposure to chemical substances such as paint, hair dyes, cleaning liquids and the use of marijuana. Viral infections affecting the lungs in childhood (e.g. bronchiolitis) could also affect airway epithelial cells, thus resulting in the development of T-helper (TH2) related asthma (Fahy, 2014).
PATHOPHYSIOLOGY
Asthma is characterized by a cumulative loss of lung function over time. Changes to airway structure and composition such as thickening of basement membrane, increased bronchial vascularity, smooth muscle hyperplasia and hypertrophy and goblet cell hyperplasia, which leads to mucous hypersecretion, also promotes to airflow obstruction. This is known as airway remodelling (Tschumperlin, 2011).
As a result of allergen exposure, inflammatory cells invade airways and releases mediators such as leukotrienes, histamine, cytokines and chemokines triggering bronchoconstriction, airway remodelling and hyper-reactivity, as shown in Table 1 (Padmanabhan, 2014).
SIGNS AND SYMPTOMS
Patients experience wheezing, cough, dyspnea and chest tightness. Symptoms may vary in frequency if treatment is received, depending on their severity and displays hypersensitization to allergens that could trigger exacerbations. The difficulty with this disease is that its symptoms often overlap with other allergies (e.g. allergic rhinitis) making it strenuous to determine the primary cause and relieve symptoms (Padmanabhan, 2014).
DIAGNOSIS
Symptoms that are alleviated by bronchodilators indicates asthma as the underlying cause. Therefore, it’s critical that tests are performed while patients are symptomatic allowing accurate diagnosis.
The age on asthma-onset should also be considered. Although asthma in children and adults share similar characteristics, there are significant differences between them. For example, adult-onset asthma develops sensitization to occupational factors and are often misdiagnosed for COPD or chronic bronchitis (Holgate et al. 2006).
As it is a hereditary disorder, a detailed patient history is required to determine whether there are any signs of family history, atopy or long-term chemical exposure. Asthma displays a decrease in FEV1 (forced expired volume in 1 second) and a reduced FEV1/FVC ratio (<70%) through analysis of spirometry (Fahy, 2014). Asthma could be detected by monitoring exhaled nitric oxide and inspecting sputum counts for bacteria or fungi infecting lungs and airway passages. Patient's response to metacholine provocation, a positive skin prick response to allergens and a fall in peak expiratory flow (PEF) are also signs of asthma (Sears, 2008). Likewise, sputum, bronchoscopic or blood analysis could indicate eosinophilic asthma by observing the abnormal eosinophils counts in blood (Wenzel, 2012). TREATMENT One of the major problems of treating asthma is the patient's noncompliance, poor inhaler technique and adherence to their treatment. Adherence results in low mortality while overuse of medication that relieve symptoms but doesn't treat the underlying cause, increases mortality among patients (Padmanabhan, 2014). Most asthma phenotypes are reversible through the use of anti-inflammatory drugs such as ICS and ??2-adrenoceptor agonists (Holgate et al. 2006). Other forms of treatment that monitors asthma and reduce symptoms are leukotriene modifiers for allergies, anticholinergics, chromones and anti-IgE. Glucocorticoids are the optimal first-line treatment which could be administered orally, as ICS or injected during exacerbations (Ortega, 2015). STRATIFIED MEDICINE IN CURRENT PRACTICE OR RESEARCH Unlike other disease, asthma has no accurate test for diagnosis and is often misdiagnosed in around 30% of patients. This is because diagnosis relies heavily on the existence of symptoms which may be variable and is caused by numerous factors (Padmanabhan, 2014).Combination of ICS and long acting ??2-adrenoceptor agonists (LABA) are the gold standard treatment, however <10% of the population are unresponsive to this treatment (corticosteroid-resistant asthma). The aim is to use pharmacogenetics in order to identify risk progression and predict treatment that would either provide efficacy or result in adverse events. Studies relating to glucocorticoids, leukotriene and ??2-adrenergic receptor pathways are based on searching for genes that affect the patient's responsiveness (Ortega, 2015). Current research aims to categorize asthma into endotypes to enhance patient outcomes. In particular, lebrikizumab, an anti-IL-13 monoclonal antibody displayed improved FEV1 among patients with high IL-13 activity while mepolizumab, an anti-IL-5 monoclonal antibody, minimized eosinophil levels and exacerbations for severe asthma patients (Poon and Hamid, 2012). . CONCLUDING REMARKS Asthma is a modern disease that has achieved a few improvements yet remains high prevalence over the years. To help fully overcome this disease, proper diagnosis and treatment of asthma endotypes should be made, based on biological guidelines, instead of empirical approaches, as shown in Table 2. This is why asthma is an excellent example of how stratified medicine would benefit this disease. By assessing the biological pathways and molecular characteristics, better diagnosis and treatments could be developed for the future.