1#Dr. Srinivas Rajagopala MD, DM (Pul. & Crit. Care Medicine) 2*Dr KumudK.Dhital BSc, MBBM.Bch, FRCS-CTh, PhD, FRACS
Dr. Srinivas Rajagopala Director, Transplant Pulmonology & Lung Failure Unit Kauvery Group of Hospitals, 8A, Murrays Gate Road, Alwarpet, Chennai, India-600018 Phone Number: 91-44-40006000; 91-44-7338738886 Email: [email protected]
Funding sources: None Conflicts of interest: None Both the authors had access to the data and a role in writing the manuscript Article type: Review article Running Head: Lung Transplantation in India Key Words: Lung Transplantation, India, end-stage lung disease, Interstitial lung disease
Lung transplantation is an established treatment for end-stage lung disease, with the first successful lung transplantation being performed almost 40 years ago on November 7, 1983 and an estimated 6000 lung transplants now being performed worldwide each year. It is however, the most complex solid organ to transplant and also, one of the last organs to be successfully transplanted; the first successful transplantation followed almost 30 years after kidneys were successfully transplanted in 1953. Some of the key time points in the history of lung transplantation worldwide (Figure 1) and in India (Figure 2) are highlighted. Cadaveric transplantation became possible in India with the “The transplantation of Human Organs” act on 8 July 1994 (THOA) by the Government of India (GoI). Health in India is a state subject and different States initially notified and performed transplantation without inter-state coordination. The first heart transplant followed almost immediately in New Delhi by 1995. The first Heart-Lung transplantation (HLTx) was performed in Chennai by Dr K.M. Cherian on May 3, 1999 utilizing cadaveric donations coordinated by MOHAN foundation across six hospitals in Chennai. After a slow start to thoracic transplants in Tamilnadu, there was a marked increase after 2008; this was related to sustained campaigns by NGOs, public awareness by a sentinel donation (“the Hithendran effect”) and governmental legislation and championship. To prevent irregularities in organ donation, revisions to THOA were made by GoI in 2011 and the revised THOA rules were notified in 2014. Tamilnadu state was the first to start a cadaver transplant program (CTP) in India by 2008; In 2014, CTP was named a government society, the “Transplant Authority of Tamil Nadu (TRANSTAN)”. Other states followed, with several Southern and Western states now having active State organ transplant organisations (SOTTOs, Figure 3). The National Organ and Tissue Transplant Organization (NOTTO) is the apex National-level organization under the Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India established in 2014 to coordinate transplants in Delhi and has been actively coordinating transplant donations between SOTTOs since 2019. Figure 3 shows the current structure of the cadaveric donation program in India. The first successful isolated lung transplant (single) in India was only accomplished in 2011 and the first bilateral lung transplantation was performed in 2013 in Chennai (Figure 2), more than 42 years after the first renal transplant in India on February 2, 1971 at CMC Vellore.
Figure 1
Figure 2
Figure 3
India has an immense burden of advanced lung disease, with an estimated 8,83,000 annual deaths and additional immense unquantified morbidity and days lost due to chronic lung disease. Chronic obstructive pulmonary disease (COPD), Post-tuberculosis lung disease (T-OPD), Bronchiectasis and interstitial lung disease contribute to a large majority of this burden. Importantly, chronic lung disease is the only etiology increasing in the top five causes of death in India and India has higher than average global COPD mortality (India accounts for ~18% of population but 32% of global COPD mortality). A conservative estimate assuming that 1% of the above patients dying annually have the resources and desire to undergo transplantation places an estimated need of lung transplants at 8800 annually in India. Of note, less than 100 lung transplants are performed annually across India at present. Almost all of these are from two cities at the current moment; Chennai in Tamilnadu and Hyderabad in Telangana with isolated single digit lung transplants in few other cities across India. Figure 4 shows the reported annual isolated lung transplants in India; it is immediately apparent that most of the activity in the field of lung transplantation in India is in the last five years and it has yet to accelerate towards fulfilling even a fraction of the needed burden.
The listing criteria for lung transplantation for some common lung diseases and contraindications are summarised in Table 1 & 2. A review of transplanted patients from India shows that Interstitial lung diseases is the most common indication for lung transplant in India, accounting for 65.9% of all transplants (Figure 5). Patient’s perceptions, affordability and rapidity of lung function decline may be responsible for these referral patterns.
Figure 4
Figure 5
The availability of lung transplantation as a reliable therapeutic option has not yet reached the lay community in India. Patient’s often have negative opinions based on self-convictions, hearsay, single reports published in the lay press or Internet. A lack of understanding of the prognosis of worsening lung disease with its poor quality of life and perception of poor post-transplant survival (at the quoted figures of 90%, 75% and 65% 1, 3 and 5-year survival) are near universal. Financial support for the surgery and post-transplant care and ability to work post-transplant are other concerns that affect the decision to undergo transplant. In a study from Chandigarh(albeit from a non-transplant centre), those who agreed for evaluation were likely to die within weeks of assent, indicating the very late acceptance in the natural course of their disease. In the time course of lung disease (Figure 6), such patients are likely to be beyond their transplant window and not eligible for transplantation. Increasing severity of respiratory illness and frailty prior to transplant strongly impact post-transplant survival with a decrement of 10% in 1-year survival with LAS scores>52. These findings are especially likely to be evident when lung transplant programs are started and at smaller centre volumes.
Figure 6
Transplant Pulmonology is fairly new and the time points for referral and listing for various diseases are often not well understood. This is especially true for idiopathic pulmonary arterial hypertension and COPD. This is likely to change by ongoing education and when patients’ follow-up with them post-transplant in a shared-care model with the Transplant team. Understanding the correct timing of referral and its implications on costs and outcomes among Pulmonologists and physicians is crucial for the large-scale success of lung transplantation in India.
India lags significantly in organ donation at0.30 ppm (donations in people per million)in 2019; less than 0.01% of the population donate. This should be compared with Spain (49.61 ppm), U.S (36.88 ppm) and U.K (24.88 ppm) to understand the intensity of paucity in donations. Also, there is significant heterogeneity in organ donation rates with South-Western India having higher than average donations; this includes Tamilnadu (1.8 pmp)and Chennai city (14 pmp). There has been a shift with a trend in higher donations over the last two years in Telangana, Maharashtra, Gujarat and Karnataka and a marked fall in donations within Tamilnadu. Several reasons can be attributed to the low rates of donation and their disparity across the country; these include awareness, literacy, religious/superstitious and legislation. The authors believe sustained campaigns and perception of societal utility is crucial for sustained donations; this can be achieved by having a large surviving productive post-transplant cohort with champions among these and governmental support to transplant to enhance access and financial support to transplant and post-transplant care. Finally, the entire transplant pathway, especially selection and priority, has to be transparent with independent oversight to avoid controversies that can dent donations. Two examples of controversies that impacted donations include the reported preferential international transplants in Tamilnadu and a litigation questioning the validity of brain death declaration in Kerala.
As compared to Western world, donors in India tend to be younger and be related to road trauma. However, less than 15% of donated lungs are utilisable when compared to 50-60% in Western settings; this is due to quality of donor lung management, intensive-care infections and thoracic trauma. A study from Chandigarh showed that 29.1% were ideal and up to 63.6% could be considered extended; donors were often considered extended based on a single PaO2/FiO2 rather than holistic assessment. In our practice, 35% are standard donors and up to 85% could be considered extended and potentially usable. However, transplant centers need to have large recipient lists to avoid turning down offers for size, sensitization and for avoiding extended donor-recipient matches. To add to the challenges, there are no organ procurement organisations to standardise donor management and maximise organ utilisation and the time-frame of SOTTO allocation does not permit donor optimisation prior to acceptance. Logistics is often the single most important reason donor lungs are not utilised and this is due to perceived allocation priority, costs involved in air-lifting organs and absence of reliable donor data, including height and blood gases. These problems are particularly magnified when dealing with sensitized donors as donor HLA is never available at the time of retrieval and good quality HLA, antibody testing and Flow cytometry are difficult to access and expensive.
COVID-19 has exposed the fault lines in cadaveric organ transplantation as it has done for the entire health-care system; the effects have been especially evident in fragmented health-care systems without strong governmental oversight like ours. On the donor side, COVID-19 has impacted organ donations, made necessary testing for organ donations more extensive and added another layer of complexity (like mandatory BAL RT-PCR for lung donors), reduced access to donated organs by reducing available transports (including commercial flights), increased costs and reduced organ utilization. On the recipient side, COVID-19 has reduced patient health-related visits by making them difficult, reduced elective transplants during waves, worsened disease severity at presentation (including more ECMO-bridging), added COVID-ARDS and fibrosis as a large cohort for transplant, increased concern for cross-infection during elective surveillance, increased virtual follow-ups and increased the specter of post-transplant viral pneumonias as an ongoing consideration.
India has the need for robust lung transplant activity in the country and this is expected to go up as COPD is better recognized and interstitial lung diseases are now being diagnosed because of widespread availability of computed tomography (CT). There are at least four mid-sized programs in the country at the present with an increasing interest from most other states. Patient and physician awareness has certainly improved after COVID-19 and will likely improve as more survivors enter the community. Governmental support for lung transplant programs is sorely needed; this should be directed at providing directives and financial support for making SOTTOs the OPOs for their respective states and maximizing organ utilisation, providing support for transporting organs, making low-resolution HLA available at organ offer, setting up sensitized recipients registry to prioritise them and finally, by providing support for transplant surgery and post-transplant care. The costs of lung transplantation should reduce with wider availability, larger center volume and earlier referral and this should positively impact the lung transplant program in the country.
Dr. Srinivas Rajagopala MD, DM (Pul. & Crit. Care Medicine) Senior Consultant, Interventional Pulmonology & Sleep Medicine, Director, Transplant Pulmonology & Lung Failure Unit
Dr KumudK.Dhital BSc, MBBM.Bch, FRCS-CTh, PhD, FRACS Program Director – Heart and Lung Transplantation
