Obstructive Airway Diseases-Overview of Indian Perspective

India has a disproportionately magnanimous burden of chronic respiratory diseases. Of the total global disability-adjusted life-years (DALYs) due to chronic respiratory diseases, 32% have been estimated to have occurred in India. COPD and asthma were responsible for 75·6% and 20% of these chronic respiratory disease-related DALYs. (1) As per a recently published report, the estimated prevalence of chronic obstructive respiratory diseases in India was 7.4%, being higher among males, in urban areas, and in northern parts of the country. (2)

Chronic Obstructive Airway Diseases & Indian Issues:

Indian Risk Factors:

The burden is higher among those living in households using solid fuels like firewood and kerosene. Smoking which is considered the main risk factor for COPD; comes in various forms in the Indian context. The Global Adult Tobacco Survey (GATS) study reported that 26% of non-smokers are exposed to Second-Hand Smoke (SHS) in the workplace, both indoors and outdoors in India. (3)

Varying Seasonal Burden of Respiratory Illnesses in India: Results of SWORD 2022 Survey:

Sharma BB et al published recently a clinically relevant paper reporting wide seasonal variations in outpatient attendance of patients with common respiratory conditions. The common respiratory diagnoses were asthma (29.8%), chronic obstructive pulmonary disease (15.6%), respiratory tract infections (11.3%), and tuberculosis (8.7%). There was an interesting seasonal trend observed for these conditions; Asthma 31.4% autumn (post-monsoon October to November) vs. 26.5% summer, COPD 21.1% winter vs. 8.1% summer, RTIs 13.3% winter vs. 4.3% summer, and tuberculosis 12.5% autumn vs. 4.1% summer, respectively. After adjustment for risk factors, asthma was significantly associated with exposure to molds, pet animals, recent travel, and rain-wetting; and respiratory tract infections with rain-wetting and recent travel. (4)

Underuse of Inhaled Corticosteroids (ICS) in India contributing to 42% of Global Asthma Deaths?:

Salvi et al published an insightful burning issue in July 2022 which reported the total amount of Inhaled Corticosteroids (ICS) used in India for asthma was worth 26.4 million in value versus the 384.16 million expected value, which is only 6.8% of the required estimated needs of the Indian population. Interestingly, when state‑wise actual sales of ICS in India were correlated with asthma mortality and disability‑adjusted life years DALYs (per 100,000 population), a significant negative correlation was established (p < 0.001 for asthma deaths and p < 0.001 for asthma DALYs). (5) It seems likely that this gap explains disproportionately high morbidity and death rates from asthma in India, and such a gap needs to be bridged urgently. (6)

Levosalbutamol Beclomethasone Combination in the Management of Obstructive Airway Illnesses:

Short-acting beta2-agonists (SABAs) are agents which possess rapid onset of broncho dilatory action, selective for the β2-receptors and provide quick symptomatic relief. Inhaled corticosteroids (ICS) have clinical utility as maintenance treatment for asthma, and are effective in reducing airway inflammation, positively influencing airway hyperresponsiveness, and reducing asthma exacerbation risk. According to scientific evidence, an ICS-containing reliever medication is superior to SABA as a reliever alone, (7) and thus could have the potential to reduce the risk of severe asthma exacerbations.

Levosalbutamol Beclomethasone Combination for Managing Obstructive Airway Diseases: Glance at Scientific Studies

Levosalbutamol reduces exacerbations and needs for rescue medications in COPD patients: Donohue JF et al conducted a study with the objective to assess the efficacy and safety of nebulized levosalbutamol in adults with chronic obstructive pulmonary disease (COPD). A multicentre, randomized, double-blind, parallel design study was designed and included 209 patients, which were randomized to receive levosalbutamol, racemic albuterol 2.5 mg, or placebo (control group) thrice daily for 6 weeks. Serial spirometry was completed after studying the drug alone at baseline, week 2, and week 6; or in a combined group with ipratropium bromide 0.5 mg at week 4. The endpoints were averaged FEV1 AUC(0–8 hrs), rescue medication use, safety parameters, and COPD exacerbations. The results demonstrated that COPD exacerbations occurred in all groups but were reported to be lowest in the levosalbutamol group. The study concluded that levosalbutamol treatment in COPD patients was generally well tolerated, produced significant bronchodilation, and improved clinical control of COPD as evidenced by greater reductions in rescue medication use with levosalbutamol treatment. (8)

Levosalbutamol Treatment Improved Airway Function in Pediatric Population: Berger WE et al, aimed to evaluate the clinical efficacy and safety of levosalbutamol metered-dose inhaler (MDI) among the pediatric population. A multicentre, randomized, double-blind, four-week study, including children (n=173) aged 4-11 years was included. The intervention arms included QID levosalbutamol 90 μg, racemic albuterol 180 μg, and placebo (2:1:1 ). Serial spirometry was carried out at baseline, week 2, and week 4 (end of study). The primary endpoint was the double-blind average peak percent (%) change in FEV1 from visit pre-dose. Secondary endpoints included the area under the FEV1 percent change from the pre-dose curve and peak%-predicted FEV1. The results of the study showed that Levosalbutamol significantly improved the least square mean peak percent change in FEV1 compared with placebo (levosalbutamol 25.6% ± 1.3% (p < 0.001); racemic albuterol 21.8% ± 1.8%; placebo 16.8% ± 1.9%). Results for levosalbutamol were similar for the other spirometry endpoints (p<0.05 vs. placebo). None of the levosalbutamol-treated patients had a peak percent change in FEV1 < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). It was noteworthy that the rate of discontinuation of treatment was lowest in the levosalbutamol group (1.3%) versus 2.6% for racemic albuterol, and 8.6% for placebo. The study concluded that levosalbutamol administered via MDI significantly improved airway function in asthmatic children with a tolerable safety profile in this patient population. (9)

Take Home Pointers

• The burden of obstructive airway illnesses is huge in Indian practice settings (1), which could have detrimental clinical short-term and long-term sequels. (10)
• With difficult-to-modify household and environmental factors like pollution, decisions regarding selecting appropriate maintenance therapy may need to be prudent. (7)
• There is great underuse of inhaled corticosteroids reported in Indian healthcare settings in the latest scientific publications and is correlated with poorer clinical outcomes. There is a burning need to sensitize all stakeholders of healthcare in this regard. (5)
• Short-acting beta2-agonists (SABAs) and Inhaled corticosteroids (ICS) based combination treatment may be useful in selected clinical scenarios pertaining to reversible obstructive airway diseases. (9)

References:

1. India State-Level Disease Burden Initiative CRD Collaborators. The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990-2016. Lancet Glob Health. 2018 Dec;6(12):e1363-e1374. doi: 10.1016/S2214-109X(18)30409-1. Epub 2018 Sep 12.

2. Daniel RA, Aggarwal P, Kalaivani M, Gupta SK. Prevalence of chronic obstructive pulmonary disease in India: A systematic review and meta‑analysis. Lung India 2021;38:506-13

3. Akansha Singh, Factors Effecting Exposure To Second-Hand Smoke In India With Special Focus On The Role Of Knowledge Of Health Hazard Of Tobacco, International Journal of Humanities and Social Sciences (IJHSS).

4. Sharma BB, Singh S, Sharma KK, Sharma AK, Suraj KP, Mahmood T, et al. (2022) Proportionate clinical burden of respiratory diseases in Indian outdoor services and its relationship with seasonal transitions and risk factors: The results of SWORD survey. PLoS ONE 17(8): e0268216. https://doi.org/10.1371/journal.pone.0268216

5. Salvi S, Madas S, Ghorpade D, Gadhave S, Barne M. Is underuse of Inhaled Corticosteroids for Asthma in India contributing to 42% of global asthma deaths?. Lung India 2022;39:331-6.

6. Kevin M, Closing gaps in asthma care in India – World Asthma Day 2022, Indian J Med Res 154, May 2022, pp 1-3 DOI: 10.4103/ijmr.ijmr_893_22

7. O'Byrne PM, Reddel HK, Beasley R. The Management of Mild Asthma. Eur Respir J 2020; in press (https://doi.org/10.1183/13993003.03051-2020.

8. Donohue JF, Parsey MV, Andrews C, D'Urzo T, Sharma S, Schaefer K, Claus R, Baumgartner RA; Levosalbutamol COPD Study Group. Evaluation of the efficacy and safety of levosalbutamol in subjects with COPD. COPD. 2006 Aug;3(3):125-32. doi: 10.1080/15412550600829190. PMID: 17240614.

9. Berger WE, Milgrom H, Skoner DP, Tripp K, Parsey MV, Baumgartner RA; Xopenex Pediatric Asthma Group. Evaluation of levosalbutamol metered dose inhaler in pediatric patients with asthma: a double-blind, randomized, placebo- and active-controlled trial. Curr Med Res Opin. 2006 Jun;22(6):1217-26. doi: 10.1185/030079906X112534. PMID: 16846555.

10. Wander A, Bhargava S, Pooni P.A, Kakkar S, Arora K. Quality of life in children with bronchial asthma. J PediatrRes.2017;4(06):382-387.doi:10.17511/ijpr.2017.i06.06