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Pharmacology: Diagnosis And Treatment

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Question:

Discuss about the case study Pharmacology for Diagnosis and Treatment.
 
 

Answer:

Introduction

The purpose of this paper is to develop an evidence-based pharmacology paper on Asthma. It will give relevant information about the diagnosis and treatment of Asthma. It will review the current literature on asthma and identify what is known and what is known about the issues present in the disease process. The paper will explain the possible approaches to the treatment of the condition and will defend the final selection of therapy from other procedures. Finally, it will refer the follow-up treatment options for patients with Asthma and accordingly create a referral plan for treatment of Asthma.

Pathophysiology of Asthma

Asthma is a pulmonary condition characterized by chronic inflammation of the airways of the lungs due to tightening of respiratory smooth muscles and events of bronchoconstriction. About 5% of children with Asthma suffer from severe exacerbation due to Asthma in spite of treatment with a variety of drugs. Severe asthma is characterized by structural changes of airways, comorbidities due to reduced lung function, airflow obstruction, and bronchial hyperresponsiveness. The common symptoms in asthma patients are wheeziness, asthma, shortness of breath and chest tightness. Approximately 26 million people are affected by the disease in U.S., and it is prevalent in 1 in 11 children (Holgate, 2012).

It may be caused by a combination of genetic and environmental factors. Exposure to air allergens and medications like aspirin triggers the disease. The disease is diagnosed by the pattern of symptoms, response to therapy and pulmonary function test in individuals. The pathophysiology of asthma is a complex process and mainly involves the following components:

Airway inflammation: The severity of asthma is divided in to acute, subacute or chronic airway inflammation. Airway inflammation is triggered by eosinophil infiltration, mucus hypersecretion, muscle hyperplasia and desquamation of epithelium. Mast cells, eosinophils, epithelial cells, macrophages and activated T-lymphocytes are responsible for airway inflammation. Airway hyperresponsiveness occurs in response to exogenous and endogenous stimuli. Pharmacologically active substance stimulates smooth muscles of airways. In chronic asthma patient, hyperplasia of smooth muscles may not be reversible. Cytokine imbalance is the reason for the rise in cases of Asthma in developed countries (Obaseki et al., 2014).

Airflow obstruction: Airflow Obstruction in Asthma patient is caused by acute bronchoconstriction, airway edema, and chronic mucous formation. The release of immunoglobin E-dependent mediator in response to aeroallergens leads to acute bronchoconstriction, and it is the manifestation of early asthmatic response. Airway edema occurs after 6-20 hours of allergen exposure, and long-standing inflammation may result in structural changes in the airway. It severely influences the reversibility of airway obstruction (Lange, 2013).

Bronchial hyperresponsiveness: Alveolar hypoxia, inconsistent airflow resistance and change in airway circulation due to hyperinflation lead to ventilation-perfusion mismatch. Generally in the early stages of asthma, patient suffers from acute hypoxemia due to inability of carbon dioxide retention. It further leads to decrease in PaCo2 and worsening of airways obstruction. In later stages, increases cardiac output lead to metabolic acidosis because of retention of carbon dioxide (Guan et al., 2014).

Age is also a factor for the continuum of disease. Recent studies on condition have revealed that deficits in lung function have been seen in only those children where the symptoms started within three years of life. This will be a major challenge in designing intervention for asthma. So it is necessary to distinguish between patients whose symptoms become evident before three years and between those whose symptoms occurs after six years age. The risk factors identified for developing asthma in children younger than three years include parental history of asthma, sensitization to aeroallergens evidence of sensitization to certain foods (Stucky et al., 2014).

 

Genomic issues in disease process

Asthma has affected millions individual worldwide. The complex etiology of asthma is related to genetic and environmental factors. The genome-wide studies on asthma have shown that genes encoding epithelial cell-cytokines, an IL-33 and IL1RL1 gene encoding IL-3 receptor, ST2 facilitate the activation of T-helper cells and lead to the pathogenesis of asthma. This finding of susceptible asthma genes has helped in expanding the understanding of the biological pathways that are dysregulated in asthma patients. Further study will assist in unraveling the complex mechanism of disease traits and the treatment procedure (Ferreira et al., 2014).

50% of asthma case occurs due to genetic susceptibility and 50% due to environmental factors. Various researches have been done regarding genetic predisposition to asthma, but still identification of all asthma genes has not yet been possible. Positional cloning study has identified five asthma genes (ADAM33, DPP10, GRPA, PHF11 and SPINK5). However, the exact function of this gene is still not clear. Some suggested that they deal with damage caused by external environment, or they exerted their effect within cells of the mucosa. Therefore the detail about exact function of asthma-related gene is still incomplete, and further research needs to do to relate epithelial barrier to gene interaction (Wan et al., 2012).

Literature reviews on asthma and its treatment

A study on genetic research on severe asthma revealed that hereditary and environmental factors are responsible for developing asthma. Many studies tried to identify the genetic cause of asthma by gene expression and epigenetic studies. It helped in the analysis of functional genes involved. This study reviewed the recent findings on genetic research studies of asthma. It revealed that genes like IL4RA and two SNPs were responsible for severe exacerbation lowered lung function in asthma patients. The heritability of asthma is up to 70 % in children and methods developed in parallel with Human Genome Project has helped in identifying the genetic causes of asthma. It also explained the susceptibility of asthma due to gene-environment interaction such as air pollution, tobacco smoke and genes involved in the anti-oxidative system, inflammatory response and innate immunity. These factors have induced the formation of airway inflammation and development of asthma symptoms (Melen & Pershagen, 2012).

Another study investigated the involvement of mast cells in the development of stress due to asthma by the activation of corticotrophin-releasing hormone (CRH). The study was dependent on epidemiological data linking stress to asthma and their explanation on how stress has an affect on asthma. The study showed that stress might be related to socioeconomic status, interpersonal conflicts, emotional stress and terrorism. It showed an association between all forms of stress and asthma manifestation. It proposed that mast cells, responsible for asthma is activated by CRH and it is secreted mainly under stress in the lungs. This leads to the release of proinflammatory mediators triggered by the cytokine. The study concluded that more research is required to investigate CRH release and reducing stress by mast cell blockers to find a new therapeutic approach to asthma (Theoharides et al., 2012).

The studies on treatment of asthma revealed that advances in biological therapies could be useful for the treatment of chronic asthma. It showed that recent research on the knowledge of asthma pathobiology has lead to the approval of humanized immunoglobulin E-targeted antibody Omalizumab. It suggested that this add-on treatment will help in assist in controlling severe cases of airway diseases. There is also much evidence to support that interleukin-5 and IL-13 specific drugs are efficient for treating asthma. It has helped to change the scenario of asthma conditions in patients. It explained that therapeutic response might differ from one individual to another, and the need is to characterize asthma subtypes so that phenotype-targeted biologics treatment can be implemented (Pelaia et al., 2012).

One literature investigated whether Omalizumab can make the difference in treating asthma exacerbation. The drug has been shown to decrease the rate of hospitalizations in patients with severe uncontrolled asthma. The study analyzed the condition under which Omalizumab is prescribed to patients and investigated whether it utilizes additional treatment to decrease the symptoms or not. It collected data on asthma treatment with oral corticosteroids but no use of Omalizumab. It assesses the risk of hospitalization for asthma two months before Omalizumab treatment. The comparison with patients who used Omalizumab showed that adjusted relative risk of hospitalization decreased significantly in patients with asthma. So it concludes that use of Omalizumab with add-on treatment is useful for reducing the risk of hospitalization due to asthma (Grimaldi-Bensouda et al., 2013).

 

Approach to literature review

The plan for collecting data was to find evidence-based pharmacology papers on asthma which revealed the reasons for the manifestation of the disease condition, and they key treatment available for the illness. They key words used were ‘pathogenesis of asthma', the socioeconomic stress of asthma, morbidity related to asthma, and recent treatment procedure for asthma. The information was collected from ScienceDirect, Pubmed data bases, Medscape data, journal articles of applied physiology, and journal articles of the American Chest Physician and content of Drug Discovery database. The approach was to find recent development in disease findings and treatment. The purpose was also to identify the drawbacks of the literature and find that information which has not yet been researched for a proper understanding of the conditions of asthma and its cause.

Published clinical guideline for asthma

The American Thoracic Society (ATS) and European Respiratory Society (ERS) developed a guideline on evaluation and treatment of asthma in children and adults. It gave detail on how to confirm the diagnosis of asthma and how to differentiate between severe asthma and mild asthma. Next step was to determine whether asthma was under control or not. Then the pathophysiology of the disease was evaluated, and it recognized factors like environmental exposure, genetic cause, adaptive immunity, activation of innate immune pathways and structural abnormality as the cause of illness. It also analyzed the efficacy of different treatment options and its particular use in special groups of patients (Chung et al., 2013).

Various possible approach for the treatment of asthma

No single approach to treatment is appropriate for all asthma patients. The need is to identify which approach will be suitable for the particular patient according to the pattern of symptoms observed in them. The goal of treatment procedure is to control chronic symptoms of asthma and minimize morbidities from acute asthmatic episodes. The approach to asthma management is divided into three age groups mainly 0-4 years, 5-11 years and above 12 years. All patients should be assessed every six months for asthma control. The following are the possible approach of treatment:

Proper use of medication: Quick relief medicines like rapid-acting beta2 agonist and anticholinergics is required in asthma patients to control sudden flare up of asthma symptoms. These are bronchodilator drugs which expand the airway and helps control exercise-induced asthma. It minimizes the symptoms, but it does not control airway inflammation. Chronic asthma patients require long-term medicines like inhaled corticosteroids, immunomodulators, leukotrienes modifiers and theophylline to reduce symptoms. It helps to reduce airway inflammation and preventing symptoms from starting point. It helps avoid the chain reaction associated with asthma symptoms. Other medicines include Cromolyn inhaled through nebulizer and Omalizumab injection shots which eliminate response generated due to allergen exposure (Fajt, & Wenzel, 2015).

Use of immunotherapy: Allergy shots are used in treating that asthma which is triggered by an allergen. It gives patient relieves from allergy symptoms and build immunity against the allergens like pollens, dust mite, etc. The dose of injection is increased with time and eventually reduces symptoms. Sublingual tablets are also used to impart immunity against certain allergens (Lin et al., 2013).

Use of anti-interleukin-5 therapy: Some asthma leads to fatal or near-fatal exacerbations. Another approach to treating symptoms of asthma includes pharmacological management by identifying specific cytokines involved. Eosinophils play key role in the progression of asthma causing airway damage due to the various mechanisms. Numerous clinical trials have shown that activation of eosinophils is regulated by interleukin-5. Therefore interfering with eosinophil function or reducing it numbers can be a useful approach for targeting cytokine receptor interaction like IL-5 (Garcia et al., 2013).

Treatment for special groups: Diagnosis of asthma in children below five years is difficult. They are generally treated by long-term control medicines. Treatment of asthma in an older patient is also difficult as they take other drugs like aspirin which may worsen the symptoms. Inhaling corticosteroids may also lead to weakness of bones. Pregnant women develop the risk of high blood pressure and protein in the urine. It may result in early birth and symptoms is managed by medicines.

 

Final selection of approach

The identification of drawbacks in each treatment option will help in selecting the final approach for the treatment process. Although long-term medications are beneficial, inhaled corticosteroids reduce child's growth rate. Asthma medications may control symptoms, but discontinuation of corticosteroid therapy leads to remission of symptoms. Use of medication also lead to life-threatening anaphylaxis which a doctor has to control immediately. Short and long-acting beta agonist bronchodilators are useful in treating patients with severe asthma but develop risk of toxicity. Often more dose is recommended than actually stated in expert guidelines. Leukotrienes modifiers had shown to prevent exacerbation when combined corticosteroid therapy. Immunotherapy helps in controlling allergen associated asthma by reducing the response to allergens. But it is often related to severe anaphylaxis leading to death. It is also risky for children below two years and pregnant women. Therefore counting on the associated risk factors, it is estimated that anti-interleukin therapy will be the best approach for treating asthma (Ober, & Yao, 2011).

Interluekin-5 has been found to play a significant role in eosinophilic inflammation in asthma. Recent research on the trial of anti-IL-5 therapy showed that it has significantly reduced the morbidity associated with asthma. IL-5 antagonism has helped patient with the hypereosinophyllic syndrome to lessen the dose of corticosteroids significantly, and it also assisted in marinating the count of eosinophils. It was found to be beneficial in treating both children and adults. This evidence further supported in the final selection of anti-IL-5 therapy as the most useful approach to treating patients with asthma and hypereosinophilic syndrome. This therapy is advisable for patients who are receiving other high doses of glucocorticoids and who continue to have high eosinophil count in sputum (Liu et al., 2013).

 

Follow up treatment

 After the final selection of therapy process for asthma, it is necessary for the patient to make an asthma response plan. It will clearly state the daily dose of medication and when it should be taken. Follow-up treatment is also dependent on how far symptoms are under control in individual patients and the frequency of asthma attacks. The asthma control may change with time, so it necessary to monitor asthma symptoms from a doctor every six months. If the symptoms are not in control, then the medication may be increased, and if it is decreasing, treatment process may be lowered. This adjustment to medication is the best way manage and control severity of asthma disease in patients (Kang et al., 2013).

Conclusion

On the whole, it can be concluded that the paper gave useful evidence-based information on the pathophysiology of asthma disease and the efficacy of treatment options. Through the review of the literature on asthma, it found out recent development about the illness. Secondly, analysis of the different approach to asthma treatment helped in defending the best choice possible for the health of patient and minimizing the symptoms of asthma. It gave useful information into additional follow treatment in such patient too.

 

Reference

Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J., ... & Boulet, L. P. (2013). International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal, erj02020-2013.

Fajt, M. L., & Wenzel, S. E. (2015). Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. Journal of Allergy and Clinical Immunology, 135(2), 299-310.

Ferreira, M. A., Matheson, M. C., Tang, C. S., Granell, R., Ang, W., Hui, J., ... & Bui, M. (2014). Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. Journal of Allergy and Clinical Immunology, 133(6), 1564-1571.

Garcia, G., Taillé, C., Laveneziana, P., Bourdin, A., Chanez, P., & Humbert, M. (2013). Anti-interleukin-5 therapy in severe asthma. European Respiratory Review, 22(129), 251-257.

Grimaldi-Bensouda, L., Zureik, M., Aubier, M., Humbert, M., Levy, J., Benichou, J., ... & Abenhaim, L. (2013). Does omalizumab make a difference to the real-life treatment of asthma exacerbations?: results from a large cohort of patients with severe uncontrolled asthma. CHEST Journal,143(2), 398-405.

Guan, W. J., Zheng, X. Y., Zheng, J. P., Boudewijn, I. M., Telenga, E. D., van der Wiel, E., ... & van den Berge, M. (2014). Small airway dysfunction in asymptomatic bronchial hyperresponsiveness and asthma. Allergy, 69(9), 1258-1259.

Holgate, S. T. (2012). Innate and adaptive immune responses in asthma.Nature medicine, 18(5), 673-683.

Kang, M. G., Kim, J. Y., Jung, J. W., Song, W. J., Cho, S. H., Min, K. U., & Kang, H. R. (2013). Lost to follow-up in asthmatics does not mean treatment failure: causes and clinical outcomes of non-adherence to outpatient treatment in adult asthma. Allergy, asthma & immunology research, 5(6), 357-364.

Lange, P. (2013). Persistent airway obstruction in asthma. American journal of respiratory and critical care medicine, 187(1), 1-2.

Lin, S. Y., Erekosima, N., Suarez-Cuervo, C., Ramanathan, M., Kim, J. M., Ward, D., ... & Segal, J. B. (2013). Allergen-specific immunotherapy for the treatment of allergic rhinoconjunctivitis and/or asthma: comparative effectiveness review.

Liu, Y., Zhang, S., Li, D. W., & Jiang, S. J. (2013). Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PloS one, 8(3), e59872.

Melen, E., & Pershagen, G. (2012). Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma. Journal of internal medicine, 272(2), 108-120.

Obaseki, D., Potts, J., Joos, G., Baelum, J., Haahtela, T., Ahlström, M., ... & Makowska, J. (2014). The relation of airway obstruction to asthma, chronic rhinosinusitis and age: results from a population survey of adults. Allergy,69(9), 1205-1214.

Ober, C. & Yao, T. (2011). The genetics of asthma and allergic disease: a 21st century perspective. Immunological Reviews, 242(1), 10-30. https://dx.doi.org/10.1111/j.1600-065x.2011.01029.x

Pelaia, G., Vatrella, A., & Maselli, R. (2012). The potential of biologics for the treatment of asthma. Nature reviews Drug discovery, 11(12), 958-972.

Stucky, B. D., Edelen, M. O., Sherbourne, C. D., Eberhart, N. K., & Lara, M. (2014). Developing an item bank and short forms that assess the impact of asthma on quality of life. Respiratory medicine, 108(2), 252-263.

Theoharides, T. C., Enakuaa, S., Sismanopoulos, N., Asadi, S., Papadimas, E. C., Angelidou, A., & Alysandratos, K. D. (2012). Contribution of stress to asthma worsening through mast cell activation. Annals of Allergy, Asthma & Immunology, 109(1), 14-19.

Wan, Y. I., Shrine, N. R. G., Artigas, M. S., Wain, L. V., Blakey, J. D., Moffatt, M. F., ... & Heaney, L. (2012). Genome-wide association study to identify genetic determinants of severe asthma. Thorax, thoraxjnl-2011.

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