|Ahead of print publication
Evaluation of medical adherence, adverse drug reactions, and quality of life in post tubercular obstructive airway disease
Vinita Awasthi1, Sarvesh Singh1, Narendra Kumar1, Manoj Kumar1, Amod Kumar Sachan1, Rajiv Garg2, Rahul Kumar1
1 Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Submission||10-Mar-2021|
|Date of Decision||15-Jul-2021|
|Date of Acceptance||15-Jul-2021|
|Date of Web Publication||06-Oct-2021|
Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Increasing incidence of tuberculosis is intensifying the posttubercular obstructive airway disease (PTOAD) in developing countries. Currently, there are no standard treatment guidelines for the management of PTOAD patients. The present study aims to evaluate the prescribing pattern, adherence, adverse drug reactions (ADRs), and quality of life (QoL) in PTOAD patients.
Materials and Methods: A prospective observational study was conducted to evaluate the prescriptions of PTOAD patients, estimating the medical adherence using Morisky 8-Item Medication Adherence Questionnaire, assessing ADRs using Hartwig's Severity Assessment Scale and assessing QoL using St. George's respiratory Questionnaire. Chi-square test, analysis of variance, paired t-test were used to compare the data. The significance of change in adherence status was assessed by Wilcoxon signed-rank test.
Results: A total of 94 prescriptions of PTOAD were analyzed. Inhaled long-acting muscarinic antagonist was prescribed to 31.9% of patients. The most common inhaled fixed dose combination was long-acting beta-2 agonist with corticosteroid, prescribed to 52.1% of patients. At final follow-up, maximum percentage of patients were found to be highly adherent, i.e. 56.4%. Overall, 34% of patients have complained about mild category of ADRs. A significant improvement in QoL was observed. At baseline, mean forced expiratory volume in 1 (FEV1) was 64.66% ±23.61%, which increased significantly to 73.34% ±21.60% on final follow-up (P < 0.001).
Conclusion: Bronchodilators are the mainstay of treatment of PTOAD patients, since both the QoL and FEV1 were improved with treatments. However, to have good treatment outcome, strict adherence along with safety of the medications must be assured.
Keywords: adherence, bronchodilators, corticosteroids, obstruction, tuberculosis
|How to cite this URL:|
Awasthi V, Singh S, Kumar N, Kumar M, Sachan AK, Garg R, Kumar R. Evaluation of medical adherence, adverse drug reactions, and quality of life in post tubercular obstructive airway disease. Perspect Clin Res [Epub ahead of print] [cited 2022 Oct 7]. Available from: http://www.picronline.org/preprintarticle.asp?id=327590
| Introduction|| |
Globally in 2019, tuberculosis (TB) has encroached a quarter of the world population and ranked among the top 10 causes of death. India ranks 1st worldwide in terms of estimated incident cases per year. Further by contributing 47% TB cases among health-care workers, globally it stands 1st. Among Indian states, Uttar Pradesh ranks 1st by holding 20% of the total number of notified cases of TB.
Most of the international and national programs of TB such as WHO End TB strategy and National TB Elimination Program of India focus on the identification of new cases, reducing its incidence, mortality, achieving a successful completion of treatment, but do not mention the complications arising due to airflow limitations after the successful management of this deadliest disease.,, The most common functional change observed in posttreatment phase of TB is obstructive airway disease. Increased incidence of TB is intensifying the posttubercular obstructive airway disease (PTOAD) in developing countries.
Currently, there are no standard treatment guidelines for the management of PTOAD patients. Hence, due to the lack of studies on PTOAD in high-burden TB countries like India and a high-burden TB state like Uttar Pradesh, we designed this study in a hope to develop a standard management protocol to minimize the silence sufferings of these patients. In the present study, evaluation of the pattern of drug utilization, adverse drug reaction (ADRs), and medical adherence was done to assess its impact on the quality of life (QoL) of these patients.
| Materials and Methods|| |
The study was a prospective observational study conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India. The study was started after taking ethical clearance from the Institutional Ethics Committee of King George's Medical University, Lucknow. A total of 94 patients coming to the Respiratory Medicine Outpatient Department (OPD) and diagnosed with PTOAD as primary disease were screened and recruited for the study. Those who satisfied the inclusion/exclusion criteria were included in the study after taking written informed consent. The total duration of the study was 12 months, i.e. June 2019 to May 2020. The total duration of data collection and follow-up for a single patient was 6 months.
Previously treated Category I pulmonary TB patients of either sex, within the age limit of 18 and above, who have taken treatment only once and ≥1 year back, presenting with chronic exertional dyspnea for which no other cause was found, and were willing to enroll in the study with consent, were included.
Patients who were <18 years, diagnosed cases of asthma and chronic obstructive pulmonary disease prior to TB, bilateral extensive bronchiectasis, severe anemia, unwilling to participate and did not give consent in the study, unable to give interview, having associated comorbidities such as heart disease, renal disease, liver disease, acquired immunodeficiency syndrome etc., terminally ill, patients with concurrent major psychiatric and/or medical illness, were excluded.
Diagnosis of PTOAD was confirmed by detail history, signs, symptoms, physical examination, spirometry (postbronchodilator forced expiratory volume in 1 [FEV1]/forced vital capacity (FVC) <0.70), and sputum acid-fast bacilli smear microscopy to rule out recurrence of TB and chest X-ray (for healed Koch's lesion). Then, a case record form designed as per the study protocol was filled. It included patient's demographic details, OPD registration number, presenting complaints and their duration, family history of TB, investigations details like spirometry which was performed using spirometer of COSMED company for the evaluation of prebronchodilator and postbronchodilator (Salbutamol 400 mcg) FVC, FEV1), FEV1/FVC ratio and grading of severity of obstruction (postbronchodilator FEV1/FVC < 0.70)], drugs prescribed. Baseline QoL was also assessed at the same time with the help of Hindi translation of self-administered St. George's respiratory Questionnaire (SGRQ). The scores were calculated with the help of latest version of SGRQ application, which was downloaded according to the compatibility of the operating system via the link http://sgrq.github.io/.
The patients were followed up at 1st month, 3rd month, and 6th month for the assessment of improvement in clinical symptoms, spirometry parameters, and QoL. Adherence to medications was also assessed, with the help of Hindi translation of Morisky Medication Adherence Scale (MMAS-8-Item) Questionnaire, completed by the patients. At the same time, ADRs were assessed using Hartwig's Severity Assessment Scale.
After the completion of the study, the data were assessed and evaluated using appropriate statistical tests.
The data were entered into the Microsoft Word Excel sheet and analyzed using Statistical Package for the Social Sciences (SPSS), version 21.0, International Business Machines (IBM) Inc. USA. The data were represented as frequencies (number), proportion (percentages), and mean ± standard deviation (SD) along with appropriate graphs and charts. Chi-square test, analysis of variance, and paired t-test were used to compare the data. The significance of change in adherence status was assessed by Wilcoxon signed-rank test. P <0.05 was considered statistically significant.
Prescribing pattern analysis
Pattern of drugs used for the treatment of PTOAD was analyzed using the WHO core prescribing indicators. These indicators were adopted and modified as per the objective of the study. The data were expressed in the form of numbers, percentage, frequency, and mean.
Quality of life analysis
QoL was analyzed using Hindi translation of self-administered St. George's respiratory Questionnaire (SGRQ). It has three components:
- Symptoms: measure distress due to respiratory symptoms
- Activity: assess effect of disturbances to mobility and physical activity
- Impact: assess psychosocial impact of disease.
A total score provides a global estimate of the respiratory health. It has 50 items with 76 weighted responses and is scored from 0 to 100. A higher score is indicative of worse respiratory health status. QoL was assessed during each follow-up and was compared to pretreatment baseline values, using mean and SD.
Medication adherence analysis
Medication adherence was analyzed using Hindi translation of MMAS-8-Item questionnaire. MMAS-8 score was calculated if the respondent answered at least 6 of 8 items. Responses of the items of the MMAS-8 were coded analogous to the English version.
“One” point is awarded when the response is “No” and “0” point is awarded when the response is “Yes” for questions 1–7. Question 8 is awarded points 4/3/2/1/0 based on the response marked by the patient. Then, a total score of all the items was calculated with a sum score ranging from 0 to 8 for adherence. The MMAS scores were categorized into the following 3 levels of adherence:
- High adherence: score <8
- Medium adherence: score 6 to <8 and
- Low adherence: score <6.
Frequencies, mean, median, and SD were calculated for the sum scores.
Evaluation of adverse drug reactions
The ADRs were recorded as numbers and percentages and their severity was assessed by Hartwig's Severity Assessment Scale. In this scale, the ADR severity is categorized into 7 levels. Level 1 and 2 are mild, Level 3 and 4 are moderate, and Level 5, 6, and 7 are severe.
| Results|| |
[Figure 1] shows that age of patients ranged from 18 to 72 years. Majority of patients were in the age group of 31–60 years (n = 57; 60.6%). There were only 3 (3.2%) cases each in age group <20 years and > 70 years, respectively. The mean age of patients was 46.22 ± 15.50 years. Majority of cases were male (57.4%) and 40 (42.6%) were female. The sex ratio of study population was 1.35.
|Figure 1: Histogram showing age dispersion of cases enrolled in the study|
Click here to view
Maximum number of patients had moderate obstruction (35.1%), followed by those having mild obstruction (33%), severe obstruction (26.6%), and very severe obstruction (5.3%).
Spectrum of prescriptions made
A total number of 400 drugs were prescribed. [Table 1] shows the spectrum of drugs prescribed. The most common and frequently prescribed inhaled single-drug bronchodilator therapy was long-acting muscarinic antagonist (LAMA) and the most common inhaled fixed dose combination therapy prescribed was long-acting beta-2 agonist (LABA) + corticosteroid (CS). Among the oral single-drug bronchodilator therapy, the most common was methylxanthines. The most common oral fixed dose combination was that of methylxanthines with expectorants.
As shown in [Table 2], MMA scores ranged from 3 to 8 at all the three follow-up intervals. The mean MMA scores were 6.67 ± 1.25, 6.63 ± 1.16, and 7.14 ± 1.28, respectively at first, second, and third follow-up intervals.
|Table 2: Distribution of cases according to level of adherence at different follow-up intervals|
Click here to view
At the first follow-up, 16 (17%) patients had low, 49 (52.1%) had medium, and 29 (30.9%) had high adherence. At the second follow-up, a total of 18 (19.2%) had low, 58 (61.7%) had medium, and 18 (19.1%) had high adherence. At the third follow-up, a total of 12 (12.8%) had low, 29 (30.9%) had medium, and 53 (56.4%) had high adherence. On evaluating the data statistically, there was a significant difference for all the inter-follow-up comparisons (P < 0.05).
[Table 3] shows that, at baseline, the mean FEV1 was 64.66% ±23.61%, while on the first, second, and third follow-up intervals, the mean FEV1 values were 64.94% ±21.98%, 68.88% ±22.00%, and 73.34% ±21.60%, respectively. At all the follow-up intervals, the mean value was higher than baseline value, yet the change was significant statistically from second follow-up onward. At final follow-up, the mean values showed an increment of 8.68% ±9.41% from initial baseline values.
|Table 3: Pattern of change in lung efficiency (percentage forced expiratory volume in 1 s) during each follow-up|
Click here to view
Quality of life
[Table 4] shows baseline mean SGRQ score of 37.41 ± 17.51, while on the first, second, and third follow-ups, the scores were 32.43 ± 16.99, 26.82 ± 16.85, and 21.05 ± 16.98, respectively. At all the follow-up intervals, the mean value was lower than baseline value and the change was significant statistically from the first follow-up onward itself. At final follow-up, the mean values showed a decline of 43.7% from initial baseline values.
Adverse drug reactions
A total of 62 (66%) patients did not have any ADR. There were 19 (20.2%) patients who had nausea/vomiting, 6 (6.4%) had dry mouth, 4 (4.3%) had hoarse voice, and 3 (3.2%) had headache. None of the ADRs required treatment change and were categorized as mild type level 1 ADR on the basis of Hartwig's severity assessment scale.
[Figure 2] shows that a total of 17 (18.1%) showed FEV1 (% Predicted) decline during the study period (−1%–−11%). However, maximum (42.6%) showed an increase up to 10% followed by those showing increase between 11% and 20% (33%) and those showing > 20% increase (6.4%).
|Figure 2: Distribution of cases according to pattern of forced expiratory volume in 1% (Predicted) Change between baseline and final follow-up|
Click here to view
| Discussion|| |
In our study, 4.26 was the average number of drugs per prescription. The most common and frequently prescribed inhaled single-drug bronchodilator therapy was LAMA and the most common inhaled FDC was LABA + CS. Rationale of prescribing LAMA in these patients was that they cause bronchodilatation by blocking the M3 muscarinic receptors in larger airways; moreover, associated adverse antimuscarinic effects are negligible with them; hence, they ensure better pulmonary efficiency. The rationale of combination of LABA + CS was that LABA stimulates the adrenergic beta-2 receptors causing bronchial smooth muscle relaxation consequently bronchodilatation and improves FEV1 in these patients, while ICS ensures inhibition of inflammation and bronchial hyperreactivity. Kim et al. also reported in their study that LAMA or LABA + ICS have been used occasionally in this condition. Among the oral single-drug bronchodilators, the most common was methylxanthines, that inhibits phosphodiesterases leading to bronchodilatation and also have anti-inflammatory property, as mentioned by Jimborean and Ianosi.
Thirty-four percent patients have complained about mild ADRs that required no treatment change of which nausea/vomiting and headache could be associated with methylxanthines as mentioned by Barr et al. and Sawynok., respectively. ICS could be a major cause for hoarse voice.
A significant improvement in QoL and pulmonary efficiency was observed at all the follow-ups, which could be attributed to the drugs (LABA + CS and LAMA) prescribed. This fact of our study is supported by Kim et al.
Since it was a single-centered study with a small sample size with short duration, the results cannot be generalized.
| Conclusion|| |
The prescribed treatments were rationally prescribed, which were associated with few mild ADRs, to which maximum number of patients were found highly adherent, that resulted in the improvement in their FEV1 and quality of life. This study gave a new way for the inclusion of PTOAD in the TB guidelines and a framework for large studies for long duration to find a standard treatment for PTOAD patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
van Kampen SC, Wanner A, Edwards M, Harries AD, Kirenga BJ, Chakaya J, et al.
International research and guidelines on post-tuberculosis chronic lung disorders: A systematic scoping review. BMJ Glob Health 2018;3:e000745.
Sarkar M, Srinivasa S, Madabhavi I, Kumar K. Tuberculosis associated chronic obstructive pulmonary disease. Clin Respir J 2017;11:285-95.
Mancuzo EV, Martins Netto E, Sulmonett N, Viana VS, Croda J, Kritski AL, et al.
Spirometry results after treatment for pulmonary tuberculosis: Comparison between patients with and without previous lung disease: A multicenter study. J Bras Pneumol 2020;46:e20180198.
Ahmed MS, Neyaz A, Aslami AN. Health-related quality of life of chronic obstructive pulmonary disease patients: Results from a community based cross-sectional study in Aligarh, Uttar Pradesh, India. Lung India 2016;33:148-53.
] [Full text]
Kastien-Hilka T, Rosenkranz B, Schwenkglenks M, Bennett BM, Sinanovic E. Association between health-related quality of life and medication adherence in pulmonary tuberculosis in South Africa. Front Pharmacol 2017;8:919.
Mahmood T, Singh RK, Kant S, Shukla AD, Chandra A, Srivastava RK. Prevalence and etiological profile of chronic obstructive pulmonary disease in nonsmokers. Lung India 2017;34:122-6.
] [Full text]
Kim CJ, Yoon HK, Park MJ, Yoo KH, Jung KS, Park JW, et al.
Inhaled indacaterol for the treatment of COPD patients with destroyed lung by tuberculosis and moderate-to-severe airflow limitation: Results from the randomized INFINITY study. Int J Chron Obstruct Pulmon Dis 2017;12:1589-96.
Jimborean G, Ianosi ES. Treatment with methylxanthines in COPD. Acta Med Marisiensis 2019;65:18.
Barr RG, Rowe BH, Camargo CA Jr. Methylxanthines for exacerbations of chronic obstructive pulmonary disease: Meta-analysis of randomised trials. BMJ 2003;327:643.
Sawynok J. Methylxanthines and pain. Handb Exp Pharmacol 2011;200:311-29.
Mohamed EE. Voice changes in patients with chronic obstructive pulmonary disease. Egypt J Chest Dis Tuberc 2014;63:561-7.
Kim HC, Kim TH, Rhee CK, Han M, Oh YM. Effects of inhaler therapy on mortality in patients with tuberculous destroyed lung and airflow limitation. Ther Clin Risk Manag 2019;15:377-87.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]