Chronic Respiratory Diseases Burden and Healthcare Facilities

ABBREVIATION USED IN THIS ARTICLE

CRDs = Chronic respiratory diseases; COPD = Chronic obstructive pulmonary disease; NCDs = Non-communicable diseases; GBDS = Global Burden of Diseases Study; CPA = Chronic pulmonary aspergillosis; ABPA = Allergic bronchopulmonary aspergillosis; IA = Invasive aspergillosis

The term chronic respiratory diseases (CRDs) refers to the airways and other structures of the lung and ignores the upper airway. The most common CRDs are chronic obstructive pulmonary disease (COPD), asthma, and occupational lung diseases. These diseases are among the leading causes of morbidity and mortality worldwide and are important contributors to the rising burden of non-communicable diseases (NCDs) globally. In addition to tobacco smoke, other risk factors for CRDs include air pollution, household smoke, and dampness (mold) exposure, occupational chemicals and dusts, and frequent lower respiratory infections during childhood. The most recent Global Burden of Diseases Study (GBD) 2017 reported that chronic respiratory diseases are the third leading cause of death globally in 2017, just behind cardiovascular diseases (31.8% of all deaths) and neoplasms (17.1%),¹ In 2017, an estimated 544.9 million individuals worldwide had a chronic respiratory disease, equivalent to a 39.8% increase compared with the figures in 1990. Chronic obstructive pulmonary disease remained the most prevalent chronic respiratory disease worldwide in 2017, accounting for 55.1% of chronic respiratory disease prevalence among men and 54.8% among women globally.¹ There were 3.2 million deaths due to COPD and 495,000 deaths due to asthma. The current COPD estimates may be substantially lower than the actual situation, which puts the burden of GOLD stage II–IV prevalence at more than 500 million.² A substantial minority of the 155 million survivors from tuberculosis (TB) are left with residual chronic lung disease.³ Asthma remains the second most prevalent chronic respiratory disease worldwide with an estimated 200 million adults and 100 million children affected.^4,5

Geographically, deaths attributable to chronic respiratory disease were most frequent in South Asia (81.2 deaths per 100,000 individuals) in 2017.¹ In India, the prevalence of COPD increased from 3.3% (28.1 million cases) in 1990 to 4.4% (55.3 million cases) in 2016, and more recently was estimated 7.1% (93.9 million cases). Chronic obstructive pulmonary disease is the second most common cause of NCD-related deaths in India. In the context of chronic respiratory diseases, advanced COPD often leads to hospitalization, with a major impact on healthcare systems. In India, an estimated 9.86 million people are admitted to hospital each year as a result of a COPD exacerbation.² Some of these exacerbations are driven by self-limiting factors such as an acute viral infection or excess smoke exposure, and resolve, but a small minority are complicated by fungal infection, that is, invasive aspergillosis (IA), which will, usually, be fatal unless detected early and treated. Asthma is increasingly common in India with 2.9% of the adult population affected, or about 40 million people.⁶

There is a wide spectrum of pulmonary fungal infections caused by ubiquitous environmental fungi, some in immunocompromised patients, some in those with underlying lung disease and less commonly in apparently normal people.⁴ These pulmonary conditions include IA, chronic pulmonary aspergillosis (CPA) including aspergilloma, hypersensitivity pneumonitis, and allergic bronchopulmonary aspergillosis (ABPA). Many patients with ABPA are misdiagnosed with TB.⁷ Invasive aspergillosis is almost always fatal if not identified and treated early. Chronic obstructive pulmonary disease is one of the many underlying risk factors for IA, including neutropenia, liver disease, diabetes mellitus, AIDS, those on immunosuppressive treatment.² The prior estimates of the annual global incidence of IA range upward from 200,000,⁸ but the diagnosis of IA in COPD patients remains difficult as expertise and laboratory infrastructure remains limited especially in low and lower middle-income countries. In fact, in this context, it is not a hyperbole that several respiratory diseases including fungal diseases such as CPA, ABPA,⁷ blastomycosis, histoplasmosis,⁹ talaromycosis, and pulmonary cryptococcosis remain hidden under the guise of pulmonary tuberculosis. Specifically, when the expertise and awareness is focused only on TB, several respiratory fungal diseases could continue to be labelled “smear negative,” ”GeneXpert negative,” and “clinically diagnosed” TB. Chronic cavitary pulmonary histoplasmosis, coccidioidomycosis, pulmonary cryptococcal infection, pulmonary hydatid disease, actinomycosis, or some subacute bacterial infections all appear radiologically similar to TB. This is not just a question of mislabeling, patients with CPA have a 20% 12-month mortality, which is addressable with antifungal therapy, but not with combined antifungal and standard anti-TB therapy because of the profound rifampicin/azole drug interaction.

Despite the unprecedented time of COVID-19, India’s National TB Elimination programme target of 2025 has achieved great strides. The strategy of bidirectional screening and testing for COVID-19 and TB, shows India’s strong commitment to eliminate TB by 2025. Given the high mortality rates due to chronic respiratory diseases in south Asia, the attention is also called on the issues of chronic respiratory diseases other than TB. Specifically, the resources should be allocated to this category of diseases, which are often given less focus than TB. First, as other respiratory diseases are often difficult to diagnose in resource-constrained settings because of the widespread lack of infrastructure and or institutes that specialize in chronic respiratory diseases. Second, diagnostic laboratories providing fungal diagnostics for respiratory diseases generally need to be strengthened otherwise incorrect treatment will impact patients directly as high mortality is directly related to misdiagnosis. In particular, this requires provision of WHO-listed essential diagnostics including fungal antigen and antibody diagnostics, fungal culture, and susceptibility testing and therapeutic drug monitoring of azole antifungal agents.^10,11

COVID-19 has highlighted the importance for countries to invest in organized health systems governed and financed in a coordinated manner. An essential component of improving global health is access to appropriate institutions/hospitals that serve the acute care needs of their communities. It is pertinent to emphasize that the respiratory institutions that are primarily dealing with chronic respiratory diseases should be strengthened and refined independent of TB so that such facilities cater to a specific large population of respiratory diseases, which are often misdiagnosed and ultimately fatal.

REFERENCES

1. GBD Chronic Respiratory Disease Collaborators. Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020;8(6):585–596. DOI: 10.1016/S2213-2600(20)30105-3.

2. Hammond EE, McDonald CS, Vestbo J, et al. The global impact of Aspergillus infection on COPD. BMC Pulm Med 2020;20(1):241. DOI: 10.1186/s12890-020-01259-8.

3. Dodd PJ, Yuen CM, Jayasooriya, SM, et al. Quantifying the global number of tuberculosis survivors: a modelling study. Lancet Infect Dis 2021;21(7):984–992. DOI: 10.1016/S1473-3099(20)30919-1.

4. Denning DW, Chakrabarti A. Pulmonary and sinus fungal diseases in non-immunocompromised patients. Lancet Infect Dis 2017;17(11):e357–e366. DOI: 10.1016/S1473-3099(17)30309-2.

5. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2163–2196. DOI: 10.1016/S0140-6736(12)61729-2.

6. 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;6(12):e1363–e1374. DOI: 10.1016/S2214-109X(18)30409-1.

7. Iqbal N, Amir Sheikh MD, Jabeen K, et al. Allergic bronchopulmonary aspergillosis misdiagnosed as smear negative pulmonary tuberculosis; a retrospective study from Pakistan. Ann Med Surg (Lond). 2021;72:103045. DOI: 10.1016/j.amsu.2021.103045.

8. Brown GD, Denning DW, Gow NAR, et al. Hidden killers: human fungal infections. Sci Transl Med 2012;4(165):165rv13. DOI: 10.1126/scitranslmed.3004404.

9. Baker J, Kosmidis C, Rozaliyani A, et al. Chronic pulmonary histoplasmosis: a scoping literature review. Open Forum Infect Dis 2020;7(5):ofaa119. DOI: 10.1093/ofid/ofaa119.

10. World Health Organization. 3rd Essential Diagnostics List Launch. Available at: https://gaffi.org/3rd-essential-diagnostics-list-launch.

11. Ashbee HR, Barnes RA, Johnson EM, et al. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother 2014;69(5):1162–1176. DOI: 10.1093/jac/dkt508.