Journal of Pharmaceutical Science and Application Volume 2, Issue 1, Page 17-22, June 2020 E-ISSN : 2301-7708

EFFECTIVENESS OF BRONCHODILATOR AND TREATMENT IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Putu Rika Veryanti1*, Ainun Wulandari1

1Department of Pharmacy, Institut Sains dan Teknologi Nasional, Jakarta, Indonesia

Corresponding author email: [email protected]

ABSTRACT Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic airway disease which is characterized by progressive airway obstruction. Bronchodilators and are the first choices of therapy in COPD patients. The goal therapy of COPD patients is to prevent , which can impact on death. But nowadays, the mortality rate due to COPD continues to increase. WHO predicts mortality from COPD in the year 2030 will be ranked third in the world. This high mortality can be caused by the ineffectiveness of therapy given. Objective: The aim of this study is to find out the effectiveness of bronchodilator and corticosteroid treatments in COPD patients. Methods: An observational study conducted retrospectively in the 2018 period at Fatmawati Central General Hospital. The effectiveness of therapy was assessed from the patient's clinical condition, gas values (PaO2 & PaCO2) and the average length of stay (AvLOS). Results: COPD was mostly suffered by males (83,33%), and the highest age for COPD was in the range of 45 years and above (90%). Bronchodilator that commonly prescribed were albuterol (30.08%), (12.2%), hydrobromide (10.57%), sulfate (8.13%), (1.63%) and (5.69%), while the corticosteroids were (17.07%), methylprednisolone (9.76%) and dexamethasone (4.88%). Bronchodilator and corticosteroid had improved patient's clinical condition (96.67% patients) and also improved PaO2 & PaCO2 values patients. There was a significant improvement in PaO2 and PaCO2 value in COPD patients (p <0.05). Conclusion: Bronchodilator and corticosteroid in COPD patients had improved patient's clinical condition and PaO2 & PaCO2 values, but the average length of stay exceeds the standard (6-9 days).

Keywords: Bronchodilator, Corticosteroid, COPD, Blood Gas Analysis, Average Length of Stay

INTRODUCTION Chronic Obstructive Pulmonary Bronchodilators and corticosteroids are the Disease (COPD) is a chronic airway disease first choices used in patients with that is characterized by slow and COPD. Bronchodilators could relax the progressive airflow. COPD is one of the smooth muscle in the airway and increase major health problems that could increase emptying while corticosteroid morbidity.[1,2] The appropriate therapy is suppresses the inflammation.[3] expected to reduce morbidity and mortality But unfortunately, the death rate due to in COPD patients. The goal therapy of COPD continues to increase. The World COPD patients is to prevent respiratory Health Organization (WHO) estimates failure, which impacts on death. deaths from COPD in the world will be -

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ranked third after coronary disease in diagnosis of COPD and received 2030.[1] One of the causes of high mortality bronchodilator and corticosteroid therapy in due to COPD is the ineffective therapy of the 2018 period. Patients with incomplete COPD. Ineffective therapy can be caused data in the medical record were excluded by -related problems.[4] A preliminary from the study. The obtained data were study has been conducted at Fatmawati patient characteristics, bronchodilator and Central General Hospital. The study found corticosteroid treatment, patient's clinical out the inappropriateness of condition, the value of blood gas bronchodilators and corticosteroids examination and length of stay of the treatment in COPD patients. The study patient. Analysis of the effectiveness of showed that there were some discrepancies bronchodilators and corticosteroids in the treatment. Six percent in the dose, 3% treatment was performed by calculating the in the route of administration and 6% in the percentage of patients who had improved choice of drug.[5] Another problem that clinical conditions, blood gas values (PaO2 could cause ineffectiveness of drug use in and PaCO2) and also by calculating the COPD is the characteristics of patients such average length of stay (AvLOS) of patients as age, comorbidities and disease severity. in the hospital. Ineffective drug therapy reduces clinical outcomes and increases patient cost.[6,7] RESULTS AND DISCUSSION Evaluation of the effectiveness of A. Patients Characteristic bronchodilators and corticosteroids The results showed that the prevalence treatment in COPD patients is an initial step of COPD in males was higher than females. to overcome these problems. The aim of this The smoking lifestyle in males affects the study is to find out the effectiveness of rate of COPD prevalence. Smoking is bronchodilator and corticosteroid known to be a major risk factor for COPD. treatments in COPD patients. Effective Based on the results of Indonesia Basic treatment could reduce patient costs so that Health Research (2013), the proportion of the rational use of drugs can be realized. male smokers aged ≥15 years was 64.9%, while the proportion of female smokers was METHODS only 2.1%. Female smokers considered to The research was a descriptive study have negative behavior based on social with the use of secondary data obtained by norms. Smoking changes in the structure a retrospective method. Data was collected and function of the respiratory tract and at Fatmawati Central General Hospital in lung tissue. Smoking will decline the lung May to June 2019. Samples used in this function. Aside from gender, age also study were 30 patients, which meet the influences the prevalence of COPD.[8] inclusion criteria, such as in patients with a

Table 1. Patient's Characteristics No Variable Patients (n) Percentage (%) 1 Gender Male 25 83.33 Female 5 16.67 Total 30 100 2 Age 36-45 years old 3 10 46-55 years old 1 3.33 56-65 years old 12 40 > 65 years old 14 46.67 Total 30 100

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Table 1 showed that COPD was mostly reducing pulmonary hyperinflation and sufferers by patients aged above 45 years inspiring muscle efficiency.[9] The use of old. Cardio- endurance increases bronchodilators gives several benefits, from childhood and reaches its peak at the including accelerating the healing time age of 20-30 years. After this age, cardio- during acute exacerbations, improving lung respiration endurance will decrease. The function and also shorten the length of stay decrease occurs because of the , heart, in the hospital.[10] and blood vessels begin to decline in In COPD patients with acute function. It's due to the decreased elasticity exacerbations, there is an increase in the of the lung parenchyma.[1] systemic inflammatory response, whereby the use of systemic corticosteroids is B. The use of Bronchodilator and effective.[10] Corticosteroids are one of the Corticosteroid in COPD Patients drugs commonly used in the treatment of The use of bronchodilators and both reversible and irreversible airway corticosteroids in COPD patients at diseases. Inhaled corticosteroids (ICS) are Fatmawati Central General Hospital shown usually used as a treatment of COPD for 3- in table 2. Based on the table, the 4 weeks. Inhaled corticosteroids are also bronchodilators which commonly able to reduce exacerbations if used in prescribed for COPD patients were combination with LABA.[11] albuterol, ipratropium bromide, fenoterol hydrobromide, terbutaline sulfate, C. Effectiveness of Bronchodilator and theophylline and aminophylline, while in Corticosteroid Treatment in COPD the group of corticosteroid were patients budesonide, methylprednisolone and The effectiveness of bronchodilators dexamethasone. and corticosteroids in COPD patients was Bronchodilators are divided into two assessed from the patient's clinical main classes, SABA (short-acting β2 condition, blood gas values (PaO2 and agonists) and SAMA (short-acting PaCO2) and the average length of stay of ). Both could be given the patient. Table 3 showed that 96.67% of in a single form or in combination for patients experienced improved clinical patients with limited activity. But treatment conditions. Initial symptoms of patients with bronchodilators (SAMA and SABA) is when hospitalized were coughing, shortness not recommended given routinely to of breath, chest pain and fever. Pathological patients with a history of exacerbations or changes of COPD are found in large patients with persistent symptoms. The use airways, small airways, pulmonary of bronchodilators improves symptoms by parenchyma and pulmonary vascular.

Table 2. Bronchodilators and Corticosteroids Treatment No Drug Patients (n) Percentage (%) 1 Corticosteroids Metil Prednisolon 12 9.76 Dexamethasone 6 4.88 Budesonide 21 17.07 2 Bronchodilators Albuterol 37 30.08 Fenoterol HBr 13 10.57 Aminophylline 7 5.69 Ipratropium bromide 15 12.2 Terbutaline sulfate 10 8.13 Theophylline 2 1.63 Total 123 100 19 DOI : https://doi.org/10.24843/JPSA.2020.v02.i01.p03 Veryanti., et al. Volume 2, Issue 1, Page 17-22, June 2020

Table 3. Patient's clinical conditions No Clinical Conditions Initial (n) Final (n) 1 Shortness of breath + Coughing + Fever 2 0 2 Shortness of breath + Coughing + Chest pain 2 0 3 Shortness of breath + Coughing 14 0 4 Shortness of breath + Chest pain 2 0 5 Shortness of breath 10 1 Total 30 1

Inflammatory cells infiltrate the surface of For clinical purposes, respiratory failure is the central airway epithelium, resulting in defined as arterial oxygen pressure (PaO2) the change of epithelium to squamous less than 60 mmHg and / or arterial carbon metaplasia. Mucous gland enlargement and dioxide pressure (PaCO2) greater than 45 goblet cell increase. These changes result in mmHg.[14] mucous hypersecretion. Table 4 showed that there was a hypersecretion causes a chronic productive significant improvement of PaO2 and cough. The dysfunction of cilia will PaCO2 value in COPD patients (p <0.05). complicate the expectoration process and Patients with a high initial PaO2 value cause airway obstruction. Chronic cough is (above normal) experienced a decrease of the first symptom in the development of PaO2 value (p= 0.027175), while the COPD. But it is often ignored by patients patient with a low initial PaO2 value (below because considered as a consequence of normal) also experienced improvement smoking or environmental exposure. condition by increasing PaO2 value Initially, the cough can disappear but then (p=0.012955). The improvement of PaCO2 persists. Chronic cough is not always patients before and after the treatment also accompanied by sputum production. In showed significantly (p=0.023548 for some cases, airflow resistance could patients with initial PaCO2 above normal develop without coughing. On the other and p=0.002707 for patients with initial hand, the changes in the small airways due paCO2 below normal). The average change to inflammation also cause airway of PaO2 patients was 54.24 mmHg, and remodeling and narrows the non-reversible PaCO2 was 16.88 mmHg. airway lumen. Inflammation, fibrosis and Another indicator that also showed the exudate will cause small airway effectiveness of treatment is the length of obstruction, which is a manifestation of stay of the patient. According to the shortness of breath that occurs in COPD Ministry of Health Republic Indonesia, the patients.[12-14] average length of stay is ideal between 6-9 The use of bronchodilator and days. In this study, 50% of patients were in corticosteroid in COPD patients could the range of ideal AvLOS. But the average prevent respiratory failure. Respiratory length of stay of COPD patients in Hospital failure could be caused by oxygenation exceeded the standards (11.4 days). The disorders, carbon dioxide disruption, or length of stay in COPD patients could be both. Arterial blood gas (ABG) is one of the affected by the presence of comorbidities. tests to diagnose lung disease. The partial Comorbidity is often cause of death in pressure of oxygen (PaO2) and the partial patients with COPD in the hospital. The pressure of carbon dioxide (PaCO2) were length of days of treatment tends to increase measured to evaluate how well the oxygen in line with the worsening condition and (O2) and carbon dioxide (CO2) moves from severity of COPD cases. The average length the lungs into the blood. The normal value of stay of a COPD patient is shorter at a for PaO2 is between 75-100 mmHg, and the mild severity compared with a more severe normal value for PaCO2 is 35-45 mmHg. severity.[15]

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Table 4. Pair t-test before and after treatment Initial condition p-value PaO2 (initial-final) p-value PaCO2 (initial-final) < Normal 0.01 0.003 Normal 0.32 0.11 >Normal 0.03 0.02

Table 5. Average Length of Stay (AvLOS) Length of Stay (days) Patients (n) Percentage (%) < 6 2 6.67 6 – 9 15 50 > 9 13 43.33 Total 30 100 Average 11.4 -

CONCLUSION 4. Kementerian Kesehatan Republik Bronchodilator and corticosteroid in Indonesia. Modul Penggunaan Obat COPD patients at Fatmawati Central Rasional. Jakarta: Kemenkes RI; 2011. General Hospital had improved the patient's 5. Banyu Aji, R. Evaluasi Penggunaan clinical condition and blood gas values Bronkodilator dan Kortikosteroid pada significantly, but the average length of stay Pasien Penyakit Paru Obstruktif exceeds the standard. Kronik (PPOK) di Instalasi Rawat Inap RSUP Fatmawati Periode 2018. Institut CONFLICT OF INTEREST Sains dan Teknologi Nasional, Jakarta; No conflict of interset in this paper. 2019. This paper was written independently 6. Andayani, T. M. Farmakoekonomi without being affiliated by another party. Prinsip dan Metodologi. Yogyakarta: Bursa Ilmu; 2013. ACKNOWLEDGMENT 7. Direktorat Jenderal Bina Kefarmasian We would like to thank The Ministry of dan Alat Kesehatan. Pedoman Research, Technology and Higher Penerapan Kajian Farmakoekonomi. Education of Republik Indonesia for Jakarta: Kemenkes RI; 2013 supporting the study. We also thank to 8. Salawati, L. Hubungan Merokok Department of Education and Research of Dengan Derajat Penyakit Paru Fatmawati Central General Hospital for the Obstruksi Kronik. Jurnal Kedokteran cooperation in this study. Syiah Kuala. 2016; 16(3) : 165–169. 9. Riley, C. M., & Sciurba, F. C. REFERENCES Diagnosis and Outpatient Management 1. Kementerian Kesehatan Republik of Chronic Obstructive Pulmonary Indonesia. Riset Kesehatan Dasar. Disease: A Review. JAMA. 2019; Jakarta: Kemenkes RI; 2013. 321(8), 786–797. 2. Kulsum, I. D., & Yunus, F. Sindrom 10. Wisman, B. A., Mardhiyah, R., & Metabolik pada Penyakit Paru Tenda, E. D. Pendekatan Diagnostik Obstruktif Kronik (PPOK). J Respir dan Tatalaksana Penyakit Paru Indo. 2016; 36(1) : 47-59. Obstruktif Kronik GOLD D: Sebuah 3. Perhimpunan Dokter Paru Indonesia. Laporan Kasus; 2015. Penyakit Paru Obstruktif Kronik 11. Pleasants, R. A., Wang, T., Xu, X., (PPOK) Edisi Buku Lengkap, Beiko, T., Bei, H., Zhai, S., & Pedoman Diagnosis dan Drummond, M. B. Nebulized Penatalaksanaan di Indonesia. Jakarta: Corticosteroids in the Treatment of Perhimpunan Dokter Paru Indonesia; COPD Exacerbations: Systematic 2011. Review, Meta-Analysis, and Clinical 21 DOI : https://doi.org/10.24843/JPSA.2020.v02.i01.p03 Veryanti., et al. Volume 2, Issue 1, Page 17-22, June 2020

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