ORIGINAL ARTICLE


https://doi.org/10.5005/jp-journals-11010-1079
Indian Journal of Respiratory Care
Volume 12 | Issue 4 | Year 2023

Analysis of Physician Prescription Patterns in Patients with Advanced Chronic Obstructive Pulmonary Disease


Arjun Khanna1https://orcid.org/0000-0001-5592-5498, Pradeep Bajad2https://orcid.org/0009-0001-3982-8468, Sourabh Pahuja3https://orcid.org/0000-0002-4302-9474, Satyam Agarwal4https://orcid.org/0009-0009-6904-3758, Isham Goel5

1–4Department of Pulmonary Medicine, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India

5Regional Medical Adviser, Cipla Medical Affairs, Cipla Pharmaceutical Company, Delhi, India

Corresponding Author: Pradeep Bajad, Department of Pulmonary Medicine, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India, Phone: +91 9468568815, e-mail: pradeepbajad@gmail.com

Received: 08 July 2023; Accepted: 04 December 2023; Published on: 18 January 2024

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is a worldwide health problem that is increasing in prevalence. There are practice differences between general physicians and respiratory physicians, and it is expected that not everyone would follow the prescribed guidelines fully.

Objectives: The objective of the study was to examine the practice standards of general physicians with postgraduate medicine degrees and evaluate their influence on disease control in COPD patients.

Materials and methods: A retrospective, observational study among 60 consecutive patients with advanced COPD patients who were seen at a tertiary care center in North India at the Department of Respiratory and Critical Care Medicine over a period of 6 months from February to July 2022.

Results: In this study, data from 60 patients were retrieved who were undergoing treatment from a randomly selected doctor of medicine/diplomate of national board (MD/DNB) physicians. Very few physicians prescribed spirometry to diagnose COPD; however, most patients had undergone a high-resolution computed tomography (HRCT) chest. Around 93.3% of patients continued using both nebulization and handheld inhalers. Around 96.6% of the study patients were prescribed short-acting bronchodilators (SABAs). None of the patients were given any prescription for smoking cessation and pulmonary rehabilitation. Influenza and pneumococcal vaccination were also prescribed to a small number of patients.

Conclusion: Overall, it appears that general physicians continue to treat COPD patients with traditional forms of treatment, and very few treat patients as per the updated guidelines.

How to cite this article: Khanna A, Bajad P, Pahuja S, et al. Analysis of Physician Prescription Patterns in Patients with Advanced Chronic Obstructive Pulmonary Disease. Indian J Respir Care 2023;12(4):325–329.

Source of support: Nil

Conflict of interest: None

Keywords: Chronic obstructive pulmonary disease, Management, Physician

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is a common debilitating illness. It is associated with significant morbidity and mortality, especially in patients with advanced disease and respiratory failure. Both international [Global Initiative for Chronic Obstructive Lung Disease (GOLD)]1 and Indian guidelines2 have been well-described for the management of patients with advanced COPD. COPD is one disease that is treated across the spectrum of physicians in our country, beginning from practitioners of traditional medicine, family physicians, general physicians, and finally, specialized chest physicians. There are bound to be practice differences between these physicians, and it is expected that not everyone would follow the prescribed guidelines fully. General physicians with a doctor of medicine/diplomate of national board (MD/DNB) medicine degrees see a large chunk of COPD and other respiratory disorders in our country. Very often, even patients with advanced disease who require tailored therapy and nonpharmacological therapy for COPD are not referred to specialist chest physicians. This study analyzes the prescription patterns of MD/DNB medicine physicians who treat advanced COPD. The study highlights common lacunae in the general practice of advanced COPD in north India. It emphasizes proper training of our physician colleagues to fill these lacune.

MATERIALS AND METHODS

A retrospective, observational study was conducted among 60 consecutive patients with advanced COPD who were seen at a tertiary care center in North India at the Department of Respiratory and Critical Care Medicine over a period of 6 months from February to July 2022. The patients were seen both in the outpatient and inpatient settings. All patients were instructed to bring their old outpatient records of at least the last two visits. Only prescriptions from MD/DNB medicine physicians were included in the study. All relevant clinical, investigational, and treatment data were collected from the hospital information system after obtaining ethical clearance from the Institutional Committee.

Inclusion Criteria

A total of 60 consecutive patients with group D COPD (as per the GOLD classification system during 2022) were included in the study. All patients had severe COPD with significant symptom burden. All patients were frequent exacerbators, defined as more than two exacerbations in the past year or any exacerbation in the past year leading to hospitalization.1 The patients whom chest physicians were seeing, non-MD doctors (MBBS general practitioners), and Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) physicians were not included in the study. The prescriptions were analyzed for these patients. The inhaled and oral drugs and other ancillary treatment being given to these patients was also noted and compiled. The data were analyzed with the help of Microsoft Excel software.

RESULT

In this study, data from 60 patients who were undergoing treatment from randomly selected MD/DNB physicians were retrieved. Patients included were advanced COPD (group D COPD) patients who were frequent exacerbators with more than two admissions in the past year. This paper categorized patients with advanced COPD as group D because the data was collected in mid-2022 when the GOLD 2022 guideline was applicable. Treatment prescriptions of these patients were analyzed, and data on inhaled/oral drugs and ancillary treatment was collated. These patients’ last 1/2 prescriptions were analyzed when they visited the clinic for OPD review or had an exacerbation.

The patients were categorized based on gender, smoking history, investigations, route of administration of drugs, inhalation devices used, different classes of medications prescribed for the management of COPD, and nonpharmacological therapy prescribed. Out of the total 60 patients, 78.3% (47/60) patients were men, and 21.6% (13/60) were women, with a mean age of 61.5 years (53–88 years) (Table 1). As seen in Table 1, most of the COPD patients were smokers; all 78.3% of males and 11.6% of females were current or past smokers. The remaining males were exposed to biomass fuel in their surroundings. While most of the patients (95%) had their high-resolution computed tomography (HRCT) chest done, only 20% of the patients had undergone spirometry. All patients had yet to complete a 6-minute walk test (6 MWT). Serum immunoglobulin E (IgE) testing was prescribed only to two patients, and they had yet to be advised to get their complete blood count test done (Table 2). Nearly all of them had used dry powder inhalers (DPI) and nebulization at some point during the treatment, while only 22% of total patients had used metered dose inhalers (MDIs) for their treatment. Among patients currently on inhaler use, 78.3% were still on a DPI and 11.6% on an MDI. Around 93.3% of patients continued using both nebulization and handheld inhalers in the form of DPI/MDI (Table 3). Almost 96.6% of the study patients were prescribed short-acting bronchodilators (SABAs), of which 37.93% were on salbutamol while 62% were on levosalbutamol. Among long-acting β adrenoceptor agonists (LABAs), formoterol was prescribed to 11.6% of patients, and only 6.6% received salmeterol. However, only 5% of the patients received formoterol in the form of nebulization. Among antimuscarinic bronchodilators, ipratropium was the most commonly (83.33%) prescribed, followed by tiotropium (3.33%), and only one prescription of glycopyrronium was found. Again, only one patient was on ultra LABA and long-acting muscarinic antagonist (LAMA) (formoterol and glycopyrronium combination).

Table 1: Sociodemographic parameters and attributed risk factors of the study population
Sociodemographic parameters N Percentage
Gender
Male 47 78.33%
Female 13 21.67%
Mean age (years) 61.5 53–88
Attributed risk factors
Female smokers 7 11.67%
Male smokers 47 78.30%
Females exposed to biomass 6 10%
Table 2: Different investigations performed during the clinical evaluation
Investigations N Percentage
Spirometry 12 20%
HRCT 57 95%
6MWT 0 0%
Table 3: Types of inhaled bronchodilators and inhalers prescribed
Inhaled bronchodilators N Percentage
Short-acting β sympathomimetics 58 96.67%
 Salbutamol 22 37.93%
 Levosalbutamol 36 62%
Long-acting β sympathomimetics
 Formoterol 7 11.67%
 Salmeterol 4 6.67%
 Formoterol-based nebulization 3 5%
Anticholinergics
 Ipratropium 50 83.33%
 Tiotropium 2 3.33%
 Glycopyrronium 1 1.69%
 Ultra LABA + LAMA 1 1.69%
Steroids
 Nebulized budesonide 54 90%
 Fluticasone 4 6.67%
 ICS + LABA (DPI/MDI) 11 18.33%
Inhalation devices prescribed
 MDI 7 11.67%
 Dry powder inhaler 47 78.33%
 Nebulization and MDI/DPI together 56 93.33%

Among steroid usage, nebulized Budesonide was prescribed to 90% of the patients, while only 6.67% were given fluticasone. Around 18.33% of the patients were on a combination of inhaled corticosteroids (ICS) and long-acting bronchodilators in an MDI or DPI form (Table 3). Around 78.33% of patients were on oral bronchodilators. Deriphylline (around 71.67%) was the most prescribed oral bronchodilator/methylxanthine. Acebrophylline and doxofylline (3.33% each) were other common bronchodilators. None of the patients have been prescribed roflumilast (Table 4). N-acetylcysteine (NAC), montelukast, and antihistamines were also prescribed as adjuvant therapy. Mucolytic and antioxidant NAC was prescribed to 53.33%, and antileukotriene montelukast was prescribed to 86.67% of study group patients. In total, 63.33% of patients were on antihistamines (Table 4). Around 45% of the patients had undergone noninvasive ventilation (NIV) in the hospital, and 10% were on home/domiciliary NIV. Long-term oxygen therapy (LTOT), where oxygen is given for >15 hours a day, was also given to 45% of patients. Around 18.33% of the patients had received invasive mechanical ventilation (IMV) (Table 4). Vaccination was received only by 37% of the patients. Out of those receiving a vaccination, 48% received the pneumococcal vaccine (77.7% had received the capsular polysaccharide vaccine, and 22.22% had received the conjugate pneumonia vaccine), while 52% of the patients received the influenza vaccine (Table 5). All the patients had been, at some point in time, given verbal smoking cessation counseling. However, none of them were given any prescription/written recommendation for the same. None of the patients were given any pulmonary rehabilitation counseling in any form. None of the patients received specific dietary counseling or body mass-muscle analysis. Only three patients had ever been referred to a pulmonologist for consultation.

Table 4: Types of oral bronchodilators, adjuvant therapies and nonpharmacological therapies prescribed
Oral bronchodilators N Percentage
Total patients on oral bronchodilators 45 75%
Deriphylline 43 71.67%
Acebrophylline 2 3.33%
Doxofylline 2 3.33%
Adjuvant therapy
 Leukotriene receptor antagonist (montelukast) 52 86.67%
 Antihistamines 38 63.33%
 NAC 32 53.33%
 Roflumilast 0 0%
Nonpharmacological therapy/respiratory support
 NIV 27 45%
 Home ventilation 6 10%
 LTOT 27 45%
 IMV 11 18.33%
Table 5: Vaccination status of the study population
Vaccination status N Percentage
Total patients on vaccination 19 37%
Pneumococcal vaccination 9 48.00%
Pneumovac 23 7 77.77%
Prevenar 2 22.22%
Influenza vaccination 10 52%

DISCUSSION

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory tract disease. It is one of the most commonly occurring noncommunicable diseases that remains poorly managed. Of the 60 patients, 78.3% were men, and 21.6% were women. The distribution of COPD prevalence being higher among males than females is congruent with the data in previous studies done in India like Mahadeo et al.3(66.19 and 33.80%), Kumar et al.4 (82 and 18%), Sinha et al.5 (54 and 46%) and Maqusood et al.6 (81 and 18%), respectively. The reason for COPD being more common in men could be attributed to the fact that the disease is less diagnosed in women, especially those residing in rural areas/peripheries, because of insufficient awareness of the disease. Their visits to healthcare professionals are also probably limited to emergencies. Also, other social factors, like smoking being more common in men than women, contribute to the higher prevalence of the former. The gold standard for the diagnosis of COPD is spirometry. In our study, only 20% of the patients had undergone spirometry, the results of which are consistent with Vanjare et al.7 where only 27.3% of physicians had used spirometry to detect COPD severity. The underutilization of spirometry, even at the specialist level, may be attributable to a lack of time, technicians, and devices. Even basic spirometry is sometimes not a part of postgraduate medical studies in our country. In contrast, other investigations, like electrocardiograms and chest X-rays, are routinely learned by physicians during their training. Moreover, spirometry is a more complex test for patients to perform and for doctors to interpret. We can overcome the above barriers by making spirometry training courses more approachable and available for doctors/paramedics/nurses/supporting staff. In our study, all patients had undergone HRCT chest. However, HRCT chest may be helpful in the identification of phenotypes as per Shah et al.,8 where the author has stated that phenotypes, as assessed by HRCT chest scan, may help in identifying patients who will benefit from bronchodilator treatment and can also help to predict severity of COPD. Another study by Purohit et al.9 suggests that although HRCT chest can be helpful in the holistic evaluation of a COPD patient, it may only be appropriate in some COPD patients, and its role may be limited to ruling out alternative diagnoses. Besides that, it is an expensive test and should be reserved for patients with no improvement in symptoms despite treatment or if suggestive by a specialist. Nearly 100% of our study population had used DPIs and nebulization at some point in life, while only 22% of the patients had used MDI for their treatment. Most COPD patients with exacerbations have decreased peak inspiratory flow rate and difficulty coordinating inhalation and device actuation. In such cases, nebulization may improve symptom control and quality of life over handheld inhalers, which patients cannot use effectively in an emergency. This is consistent with the results of Sharafkhaneh et al.;10 author demonstrated that most patients and caregivers were satisfied with nebulization therapy, reporting benefits in symptom relief, ease of use, and improved quality of life. However, nebulizer accessories are potential sources of infection and should be cleaned after every use and disinfected daily. Most general practitioners also have paramedics who are given the task of nebulizing patients and educating them. However, as per Guleria et al.,11 not all paramedics are adequately trained and do not follow the required cleaning and disinfection protocol. Thus, it is imperative to develop and propagate standardized protocols on “good nebulization practices” and conduct training programs for paramedics that can be followed at clinics and hospitals. It has been observed that longer nebulization time causes inconvenience, resulting in reduced patient compliance. But despite several known drawbacks associated with nebulized therapy, COPD patients and their caregivers are becoming increasingly satisfied with nebulized drug delivery mainly because of the minimal coordination and patient effort required, leading to better compliance.

Healthcare professionals must have adequate knowledge of the inhalation devices available to patients and their key characteristics. They must select the best device to meet patients’ needs and preferences. The most essential requirement is to spend adequate time training and retraining about using and disinfection inhalation devices at every use. As per GOLD guidelines, 20221 COPD management guidelines recommend ICS in group D category patients. According to GOLD guidelines 2022, ICS benefits a subgroup of COPD patients with frequent exacerbations, ≥2 exacerbations/year. Still, there is less likelihood that the patient will respond to ICS in COPD patients if blood eosinophils <100 cells/µL. In our study population, around 18.33% of the patients were on a combination of ICS and long-acting bronchodilators either in an MDI or DPI form, while in other Indian studies by Maqusood et al.6 (26.7%) and Kumar et al.4 (39. 3%) comparatively higher number of patients were on ICS and LABA combination, respectively. Long-acting bronchodilators (LABA/LAMA) were the choice of drugs recommended for group D COPD patients; however, in this study, short-acting muscarinic antagonists (SAMA) and SABAs are the most prescribed bronchodilators. Levosalbutamol (62%) was the most prescribed SABA, and Ipratropium (83.35%) was the most prescribed antimuscarinic bronchodilator. These findings are similar to those demonstrated in a study by Mahadeo et al.3 where levosalbutamol and ipratropium were used in fixed combinations in maximum prescriptions. The finding was, however, inconsistent with the results of Kumar et al.,4 where salbutamol (65.89%) was the most prescribed SABAs. Only one prescription of glycopyrronium was found in our study. As per GOLD 2022,1 a combination of LABA/LAMA is better than LABA and LAMA alone for reducing exacerbations; however, only one prescription of glycopyrronium with formoterol was found. Among LABAs, most of the time, formoterol was prescribed to 11.6, and 5% of the patients received formoterol in nebulization form. Among steroids usage, nebulized budesonide was prescribed to 90% of the patients, the findings congruent with those studies by Mahadeo et al.3 (84.5%) and Maqusood et al.6 (77.02%). Budesonide is the choice of steroid and formoterol because of a vast pool of evidence for efficacy and safety in patients with COPD exacerbations. (Unni et al.12 and Veettil et al.13). In our study, around 78.33% of patients were on oral bronchodilators. Deriphylline (around 71.67%) was the most prescribed methylxanthine; however, in a study by Maqusood et al.6 acebrophylline (64.8%) was the most common. Mahadeo et al.3 (69.7%) found that combining theophylline with etophylline was the most prescribed.

None of the patients was prescribed roflumilast in our study, while GOLD 20221 recommended using phosphodiesterase-4 inhibitors in addition to inhaled bronchodilators in patients with severe airflow limitation. GOLD 20221did not recommend methylxanthines due to the increased risk profile unless other long-term bronchodilators are unavailable or unaffordable.. It also states that they only give modest symptomatic benefits in stable COPD patients. It might be assumed that the use of theophylline has come down comparatively due to inhaled bronchodilators; however, our study data suggests that the use of oral bronchodilators is still rampant. One reason could be that clinicians are familiar with its use, as theophylline has been used conventionally as a bronchodilator for asthma and COPD over many decades. Moreover, it is readily available, easy to administer, and more economical than inhaled patient therapies. NAC, montelukast, and antihistamines were also prescribed as adjuvant therapy in our study. Mucolytic and antioxidant NAC were prescribed to 53.33% of our study population. GOLD 20221recommended its use only in selective COPD patients not receiving ICS. Evidence shows that regular treatment with mucolytics such as NAC may reduce exacerbations, as demonstrated by Zheng et al.,14 and modestly improve health status/quality of life (Salve et al.)15 As per NICE guidelines, mucolytic drug therapy is recommended only if the symptomatic improvement is required (for example, reduction in the frequency of cough and sputum production), as demonstrated in a study by Kale et al.16 GOLD 20221 also stated that leukotriene modifier use has limited evidence in COPD. Montelukast was prescribed to 86.67% of our study group patients, which is inconsistent with the studies of Mahadeo et al.3 and Kumar et al.4 where montelukast was prescribed to only 3.87 and 4. 2% of the study group patients, respectively. However, in the study by Maqusood et al.6 at a tertiary care college/hospital in Uttar Pradesh, India, 54.05% of patients were prescribed montelukast. In total, 63.33% of patients were on antihistamines, which is considerably high compared to the findings in Kumar et al.4(4.48%). Both the centers in other studies (Mahadeo et al.3 and Kumar et al.4) were tertiary care government colleges/hospitals from the medicine/pulmonary department. In contrast, our study data was collected from private practitioners. That is probably the reason for the considerable difference in using NAC/leukotriene receptor antagonists/antihistamines in private and government setups owing to cost or other factors. This implies that COPD management is not always per GOLD guidelines among physicians, and treatment is individualized on a case-to-case basis.

Among the study population, 45% of the patients had undergone NIV in the hospital, and 10% were on home/domiciliary NIV use. Long-term nocturnal NIV has been applied in patients with chronic alveolar hypoventilation for decades. As per GOLD 2022,1 NIV should be the first mode of ventilation used in COPD patients with acute respiratory failure who do not have any absolute contraindications because it improves gas exchange, reduces work of breathing, need for intubation, decreases hospital stay duration, and improves survival. Around 18.33% of the patients in our study received IMV. GOLD 20221 recommended using IMV in hypoxemic patients unable to tolerate NIV. LTOT was also given to 45% of patients who received oxygen for >15 hours daily. LTOT is recommended by GOLD 20221 for COPD patients with severe chronic hypoxemia and has been shown to reduce mortality in this population. In our study, both pneumococcal and influenza vaccinations were received by 37% of the patients overall. The number of patients receiving vaccination in our study was much higher than the findings by Maqusood et al.6 where only 5.40% received a vaccination, and that too only influenza. GOLD 20221 recommended that influenza vaccination and protection against pneumococcal infection are vital in patients with COPD and should be recommended to all eligible individuals. Guidelines highlight the reduction of severe illness/acute exacerbations and death as the efficacy endpoint after influenza vaccination. Recent data from a prospective, multicenter, cohort study by Mulpuru et al.17 demonstrated a 38% reduction in hospitalizations in patients with COPD who received influenza vaccination compared with those who had not been vaccinated. For pneumococcal vaccination, the guidelines indicated that the 23-valent pneumococcal vaccine has demonstrated a reduction in community-acquired pneumonia in patients with COPD who are younger than 65 years. In patients with COPD who are 65 years or older, the 13-valent pneumococcal vaccine has been effective in reducing bacteremia and invasive severe pneumococcal disease. Vaccination with both influenza and pneumococcal vaccines may produce an additive effect that reduces exacerbations more effectively than either vaccine alone. All the patients had been given verbal smoking cessation counseling at some point. However, none of them were given any prescription/written recommendation for the same. None of the patients were given any pulmonary rehabilitation counseling in any form, similar to the findings of the study by Maqusood et al.6 Only three patients were referred to a pulmonologist for consultation. GOLD 20221 guidelines recommended that brief tobacco counseling is effective, and every tobacco user should be offered such advice at every point of contact with healthcare providers as they are cost-effective interventions. None of the patients received specific dietary counseling or body mass-muscle analysis.

CONCLUSION

Our study concludes that group D COPD was more prevalent in men, and smoking was the most common risk factor. Very few physicians prescribed spirometry to diagnose COPD; however, most patients had undergone HRCT chest. The most prescribed bronchodilators were short-acting β-2 agonists and short-acting antimuscarinics. LABA, LAMA monotherapy, and combination therapy of LAMA/LABA or LABA/ICS or LABA/LAMA/ICS were prescribed in very few patients. The most prescribed corticosteroid was nebulized budesonide. A significant portion of patients were prescribed oral bronchodilators, and the use of methylxanthines by general physicians is also prevalent in COPD patients. Roflumilast was not prescribed to any patient. The use of NIV and LTOT was commonly seen among the nonpharmacological therapies given. At the same time, none of the prescriptions had mentioned a written smoking cessation plan, nicotine replacement therapy, dietary counseling, body mass-muscle analysis, or pulmonary rehabilitation. Influenza and pneumococcal vaccination were also prescribed to a small number of patients. Significantly, few patients were referred for a pulmonologist consultation. Overall, it appears that general physicians continue to treat COPD patients with traditional forms of treatment, and very few treat patients as per the updated guidelines.

Limitation

It was conducted in a small group of patients and a single-center study. More extensive studies are needed in this regard. Not all patients had all their previous prescriptions; some were missing.

ORCID

Arjun Khanna https://orcid.org/0000-0001-5592-5498

Pradeep Bajad https://orcid.org/0009-0001-3982-8468

Sourabh Pahuja https://orcid.org/0000-0002-4302-9474

Satyam Agarwal https://orcid.org/0009-0009-6904-3758

REFERENCES

1. Global Strategy for the. Diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD Executive Summary. https://goldcopd.org/2022-gold-reports/

2. Gupta D, Agarwal R, Aggarwal AN, et al. COPD Guidelines Working Group Guidelines for diagnosis and management of chronic obstructive pulmonary disease. Lung India 2013;30(3):228–267. DOI: 10.4103/0970-2113.116248

3. Mahadeo PS, Sudhir LP, Anand SK, et al. Study of drug prescription pattern among COPD patients admitted to medicine in-patient department of tertiary care hospital. Int J Basic Clin Pharmacol 2017;6(9):2228–2232. DOI: 10.18203/2319-2003.ijbcp20173750

4. Kumar S, Madhuri G, Wilson A, et al. Study of prescribing pattern of drugs in chronic obstructive pulmonary disease in tertiary care teaching hospital. Indian J Pharmacy Practice 2019;12(3):161–166. DOI: 10.5530/ijopp.12.3.36

5. Sinha B, Vibha, Singla D, Chowdhury R. An epidemiological profile of chronic obstructive pulmonary disease: a community-based study in Delhi. J Postgrad Med 2017;63(1):29–35. DOI: 10.4103/0022-3859.194200

6. Maqusood M, Khan FA, Kumar M. A study of prescription pattern in the management of copd in a tertiary care hospital. Ann Int Med Dent Res 2016;2:159–163. DOI: 10.21276/aimdr.2016.2.3.39

7. Vanjare N, Chhowala S, Madas S, et al. Use of spirometry among chest physicians and primary care physicians in India. NPJ Prim Care Respir Med 2016;26:16036. DOI: 10.1038/npjpcrm.2016.36

8. Shah U, Jayalakshmi TK, Mirchandani L, et al. COPD phenotypes according to high resolution CT scan findings. D Y Patil J Health Sci 2014;1(2):1–6.

9. Purohit S, Dutt N, Kumar S. High resolution computed tomography in chronic obstructive pulmonary disease patients: do not forget radiation hazard. Lung India 2016;33(5):582–583. DOI: 10.4103/0970-2113.189006

10. Sharafkhaneh A, Wolf RA, Goodnight S, et al. Perceptions and attitudes toward the use of nebulized therapy for COPD: patient and caregiver perspectives. COPD 2013;10(4):482–492. DOI: 10.3109/15412555.2013.773302

11. Guleria RJ, Thakkar KM. Nebulizer practices among paramedics in India. Lung India 2019;36(1):80–81. DOI: 10.4103/lungindia.lungindia_147_18

12. Unni A, Jayaprakash KA, Yadukrishnan MC, et al. Drug utilization pattern in chronic obstructive pulmonary disease inpatients at a tertiary care hospital. Int J Pharm Pharm Sci 2015;7(11):389–391.

13. Veettil SK, Rajiah K, Kumar S. Study of drug utilization pattern for acute exacerbation of chronic obstructive pulmonary disease in patients attending a government hospital in kerala, India. J Family Med Prim Care 2014;3(3):250–254. DOI: 10.4103/2249-4863.141622

14. Zheng JP, Wen FQ, Bai CX. High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study. COPD 2013;10(2):164–171. DOI: 10.3109/15412555.2012.732628

15. Salve VT, Atram JS. N-acetylcysteine combined with home based physical activity: effect on health related quality of life in stable COPD patients- a Randomised Controlled Trial. J Clin Diagn Res 2016;10(12):16–19. DOI: 10.7860/JCDR/2016/23668.8980

16. Kale SB, Patil AB, Kale A. Effects of administration of oral n-acetylcysteine on oxidative stress in chronic obstructive pulmonary disease patients in rural population. Int j basic Clin Pharmacol 2016;5(3):775–781. DOI: 10.18203/2319-2003.ijbcp20161518

17. Mulpuru S, Li L, Ye L, et al. Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN). Effectiveness of influenza vaccination on hospitalizations and risk factors for severe outcomes in hospitalized patients with COPD. Chest 2019;155(1):69–78. DOI: 10.1016/j.chest.2018.10.044

________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.