Assessment of Adverse Drug Reactions and Health-Related Quality of Life Among COPD Patients Receiving Triple Inhaler Therapy: A Prospective Observational Study

Abstract

Background:Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Triple inhaler therapy comprising inhaled corticosteroids (ICS), long-acting ?? agonists (LABA), and long-acting muscarinic antagonists (LAMA) is widely used in moderate to severe COPD. However, prolonged use may lead to adverse drug reactions (ADRs) that could influence treatment adherence and health-related quality of life (HRQOL).Objective:To evaluate the prevalence and pattern of ADRs and to assess their association with HRQOL among COPD patients receiving triple therapyMethods:A prospective observational study was conducted over six months in the respiratory medicine department of a tertiary care hospital. A total of 129 COPD patients aged ?40 years receiving triple therapy (tiotropium, formoterol, budesonide) were included. ADRs were assessed using the Naranjo causality scale, and HRQOL was measured using the St George’s Respiratory Questionnaire (SGRQ). Statistical analysis was performed using SPSS with chi-square testing.Results:Among 129 participants, males constituted 58% and the majority were aged 60–69 years. ADRs were reported in a substantial proportion of patients, with dry mouth and oral candidiasis being the most frequent. Most ADRs were classified as probable or possible. HRQOL scores indicated moderate to severe impairment. There was no statistically significant association between ADR occurrence and HRQOL; however, age and comorbidities showed a significant relationship with poorer QOL outcomes.Conclusion:Triple therapy is associated with a notable incidence of ADRs, although these did not significantly affect HRQOL. Comorbidities and aging appear to be stronger determinants of reduced quality of life. Continuous monitoring and individualized management strategies are recommended to optimize outcomes.

Keywords

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic inflammatory response to noxious particles and gases. It represents a major global health burden and is currently one of the leading causes of death worldwide.¹ The disease significantly affects functional capacity, increases healthcare utilization, and reduces patients’ quality of life.²

 Management of COPD focuses on symptom control, reduction of exacerbations, and improvement of health-related quality of life. Pharmacological therapy remains central to disease management, with inhaled medications forming the cornerstone of treatment. Long-acting bronchodilators such as LABAs and LAMAs are commonly used for maintenance therapy, while inhaled corticosteroids are recommended for patients with frequent exacerbations or severe disease.^3-8 Triple therapy combining ICS, LABA, and LAMA has demonstrated improved lung function, reduced exacerbation rates, and better symptom control compared with dual therapy. Despite these benefits, long-term inhaler use may result in ADRs such as oral candidiasis, dry mouth, cardiovascular effects, and dysphonia.⁸ These reactions may influence medication adherence and potentially impact quality of life.⁹ Health-related quality of life (HRQOL) is an important outcome measure in COPD management as it reflects the patient’s perception of disease burden. Evaluating both ADRs and HRQOL provides insight into real-world effectiveness and safety of treatment regimens.¹⁰ This study was therefore conducted to assess ADR patterns and their relationship with HRQOL among COPD patients receiving triple inhaler therapy in a clinical setting.¹¹

2. Methods

Study Design and Setting

A prospective observational study was conducted over a period of six months in the respiratory medicine department of a tertiary care hospital.

Study Population

Patients aged 40 years or older diagnosed with COPD according to GOLD criteria and receiving triple inhaler therapy for at least six months were included. Patients with asthma, severe cardiac illness, or newly diagnosed COPD were excluded.

Sample Size

The calculated sample size was 129 based on prevalence estimates and standard statistical formula.

Data Collection

Demographic details, clinical characteristics, smoking status, comorbidities, and therapy duration were collected using a structured data collection form. ADRs were identified through patient interviews and clinical assessment.

Assessment Tools

ADR Assessment:

Causality was determined using the Naranjo Adverse Drug Reaction Probability Scale.

Quality of Life Assessment:

HRQOL was measured using the St George’s Respiratory Questionnaire, which evaluates symptoms, activity limitation, and disease impact.

Statistical Analysis

Data were analyzed using SPSS software. Descriptive statistics were used for demographic variables. Associations between ADRs, demographic factors, and HRQOL were analyzed using chi-square test with significance set at p < 0.05.

Ethical Considerations

Ethical approval was obtained from the Institutional Ethics Committee, and informed consent was obtained from all participants.

3. RESULTS

3.1 Demographic Characteristics

A total of 129 patients were enrolled, of whom 75 (58%) were male and 54 (42%) were female. The majority of participants belonged to the 60–69-year age group. Smoking history was present in a large proportion, with smokers and ex-smokers accounting for more than two-thirds of the study population.

Table 1. Baseline Demographic and Clinical Characteristics (n = 129)

3.2 Adverse Drug Reactions

ADRs were observed in a significant proportion of patients. The most commonly reported ADRs included:

Dry mouth

Oral candidiasis

Palpitations

Most ADRs were classified as probable or possible according to the Naranjo scale.

3.3 Quality of Life Assessment

SGRQ scores indicated moderate to severe impairment in HRQOL among the majority of participants. Older patients demonstrated poorer QOL scores compared with younger patients.

3.4 Association Analysis

No statistically significant association was observed between ADR occurrence and HRQOL scores. However, comorbidities such as hypertension and diabetes showed a significant relationship with poorer quality of life outcomes.

4. DISCUSSION

This study evaluated ADR patterns and HRQOL among COPD patients receiving triple inhaler therapy. The findings demonstrated a higher prevalence of ADRs, consistent with previous studies reporting local and systemic effects associated with long-term inhaler use.¹² Dry mouth and oral candidiasis were the most frequent reactions, which can be attributed to anticholinergic effects of LAMA and local immunosuppressive effects of inhaled corticosteroids. Despite the presence of ADRs, their impact on HRQOL was not statistically significant, suggesting that symptom burden and comorbidities may play a more prominent role in determining patient-perceived health status. Age emerged as a significant determinant of poorer HRQOL, likely due to reduced physiological reserve and increased comorbidity burden in elderly populations. Similarly, the presence of chronic conditions such as hypertension and diabetes was associated with reduced quality of life, highlighting the importance of comprehensive disease management. The findings support the clinical effectiveness of triple therapy while emphasizing the need for regular monitoring of ADRs. Patient education regarding inhaler technique and oral hygiene may help minimize local adverse effects.

CONCLUSION

Triple inhaler therapy in COPD patients is associated with a notable prevalence of ADRs, although these reactions did not significantly influence HRQOL. Age and comorbidities were stronger predictors of reduced quality of life. Routine pharmacovigilance and individualized management strategies are essential to optimize therapeutic outcomes.

6. Limitations

Single-center study

Moderate sample size

Short follow-up duration

Lack of longitudinal assessment

7. Clinical Implications

Regular ADR monitoring should be incorporated into COPD management

Comorbidity control may improve overall QOL

Patient counseling can reduce preventable ADRs

8. Declarations

Ethical Approval: Obtained from Institutional Ethics Committee

Funding: None

Conflict of Interest: None declared

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