Asthma in developing countries in the Asia‐Pacific Region (APR)

There is growing interest in the epidemiology of asthma in developing countries, especially in the Asia‐Pacific Region (APR). A number of reviews have been published in this field, but a comprehensive synthesis of overall data has not been reported. Here, we summarized the burden, risk factors and challenges of asthma management in developing countries with a specific emphasis on the APR by consolidating evidence from both systematic and narrative reviews published up until February 2023. We found that although asthma prevalence in low and low‐middle‐income countries (LMICs) is known to be generally lower compared to high‐income countries, the burden is substantially greater. Studies conducted in APR LMIC have reported a range of risk factors, including pre‐ and post‐natal factors, environmental considerations, lifestyle measures, individual features and genetics. The low and inequitable distribution of quality preventive and curative health care, a lack of advanced diagnostic measures, non‐availability and non‐affordability of novel therapeutics, cultural beliefs and practices, and diverse disease phenotypes make it challenging to achieve optimal asthma control in the region. Hence, we call for the development of a region‐specific blueprint for action to mitigate this challenging situation, to help reduce the burden of asthma in APR LMIC.


INTRODUCTION
Asthma has health and economic consequences on the individuals and health care systems worldwide.Although asthma is a growing challenge in many parts of the world, until recently published studies and reviews have focused mainly on the Western world where the prevalence of asthma started to rise in the second half of the last century; well before the rise in developing countries.This increase has led to multiple investigations of both children and adults, including large multi-country studies such as European Community Respiratory Health Survey and International Study of Asthma and Allergies in Children (ISAAC). 1,2These studies showed substantial variation in the prevalence of asthma across countries, suggesting the importance of country-specific risk factors potentially due to its strong links to environmental and genetic factors.Large studies that were set-up to investigate natural history of childhood asthma in Western countries are now continuing well into the middle-age, allowing investigation of both the effects of childhood asthma on lifetime lung function patterns and the effects of early life risk factors (including preconception adverse exposures) on adult asthma. 3,4sthma has not been considered a major public health issue in developing countries as the prevalence is relatively low.However, in early 2000, ISAAC showed the prevalence of asthma in school-age children had increased in some low-income and low-middle-income countries (LMICs). 5nterestingly, a recent study using similar methods to ISAAC investigated time trends across the last three decades and showed a decrease in the prevalence of wheeze in school-age children in low-income countries but an increase in LMICs. 6Lack of accurate reporting and a low number of studies may be partly responsible for the reduction observed in low-income countries. 7Furthermore, asthma in developing countries is known to be more commonly associated with severe symptoms, although the prevalence of asthma is less common compared to the Western world. 8This pattern may reflect late diagnosis, under-treatment, and poorer overall response to the disease in these resource-poor settings. 9In addition, there is a high prevalence of asthmarelated risk factors, including exposure to passive smoking, air pollution, and poor housing in developing countries, especially in the Asia-Pacific Region (APR).Rising prevalence of asthma in developing countries combined with the high rate of asthma risk factors affecting both children and adults, impacts the socio-cultural an economic stability of LMICs.These observations, together with the assumption of low prevalence, suggest researchers may have overlooked the potential impact of asthma on developing nations, especially in the APR.
To address this knowledge gap and investigate the implications of asthma in developing countries, we reviewed burden, risk factors and challenges of asthma management in developing countries with a specific emphasis on the APR.Since the majority of developing countries in the APR are now classified as LMIC (Table S1 in the Supporting Information), the focus of this article will be LMIC in the region (hereafter referred to as APR LMIC). 10 We conducted a systematic search to identify articles for this review.We utilized the PubMed database, with narrow search terms to identify papers published until 10th February 2023.They are as follows: Prevalence: "Prevalence" AND "Asthma" AND ("Asia-Pacific" OR "developing countr*" Burden: "Burden" AND "Asthma" AND ("Asia-Pacific" OR "developing countr*") Risk factors: "Risk factor*" AND "Asthma" AND ("Asia-Pacific" OR "developing countr*") Diagnosis and management: "Challenges" AND ("Diagnosis" OR "Management") AND ("Asia-Pacific" OR "developing countr*").
We have consolidated evidence from both systematic and narrative reviews when writing our review.Additionally, we also searched the reference lists of reviews to identify eligible papers.Occasionally, when we could not find studies conducted specifically in the whole of APR (e.g., when searching for risk factors), we referred to studies conducted in South and East Asia, which are included in the APR.Our review is structured into the following sections: asthma prevalence and disease burden, risk factors of asthma and challenges in asthma management.

ASTHMA PREVALENCE AND DISEASE BURDEN
Our review found that although asthma prevalence is lower in APR LMIC compared to high-income countries, asthma burden is higher.

Prevalence
Estimating the global asthma prevalence accurately is demanding as different questionnaires have been used to ascertain asthma symptoms, which are often open to subjective interpretation.The World Health Survey (WHS) looked at adult clinical asthma prevalence using a standardized questionnaire designed by the World Health Organization (WHO), which identified Australia, Sweden and UK as having highest disease prevalence globally 11,12 (Figure 1).Vietnam and China, two Asian nations, were among the three countries with lowest adult asthma prevalence.Similarly, a low prevalence of current wheeze among children aged 13-14 years was noted in APR LMIC in the ISAAC Phase Three study (ISAAC-3). 13tudies have postulated that the lower asthma prevalence observed in developing countries could be due to lower rates of atopy, higher rates of breastfeeding, larger household size, exposure to microbes ("hygiene hypothesis"), higher rates of cross infection early in life, and rurality. 14Genetic factors may also play a role; however, the observation of marked variations of asthma prevalence among different cities within the same country suggests this risk to be more related to environmental and lifestyle causes.Nevertheless, it is now acknowledged that the prevalence of asthma and allergies are increasing rapidly in the developing countries, especially APR, which has been attributed to rapid urbanization and escalating environmental pollution. 15

Burden
Analysis of the WHO mortality database revealed that agestandardized asthma mortality during 2001-2010 for all ages was higher for LMIC compared to high-income countries. 16ortality distribution was highest for LMIC in the African continent, while Philippines, Maldives and Thailand were among the leading in APR.A recent review on chronic respiratory diseases found a staggering 96% of asthmarelated deaths and 84% of disability-adjusted life years (DALY) worldwide in LMICs. 17 Lancet review on asthma in LMICs has shown that although asthma ranked as the 28th most common cause of disability-adjusted years of life lost (YLL) worldwide in 2015, it was the 8th highest cause of YLL in Oceania (Fiji, Kiribati, Marshall Islands, Micronesia, Papua New Guinea, Samoa, Solomon Islands, Tonga, Vanuatu). 8The review also found that many adult asthmatics are only identified in emergency rooms and there is lack of proper follow-up and treatment.Similarly, asthmatic children in LMICs were found to be more severely symptomatic than those from developed countries.It is worthwhile to note that in ISAAC-3 over 50% of children with asthma in LMICs had severe symptoms and over 30% of these severe asthmatics never had a formal diagnosis of asthma. 13In Sri Lanka, 23% of children aged 3-6 years from a rural community had wheezing in the preceding year. 18Importantly, 7% of these children had symptoms suggestive of severe asthma of which two-thirds were not diagnosed as asthmatics by a physician.
The Asthma Insights and Reality in Asia-Pacific Study (AIRIAP) in 2000 investigated asthma burden in eight countries and demonstrated absence from school and work among 36.5% children and 26.5% adults suffering from asthma, respectively. 19Unscheduled health care visits due to poor control was noted in 43.6% of asthmatics across all ages in the preceding year.Unfortunately, this study did not provide country-specific details and it was conducted over 20 years ago.As there may be a shift in some low-income countries to middle class over time in regard to lifestyle factors (e.g., diet, sedentary behaviour) but not healthcare resources, a replication of this study is urgently needed.
The cost of asthma varies from country to country.This involves direct and indirect cost to patients, their families and the health system and incorporates expenses for physician visits, medications, emergency room visits, hospital admissions, days out of school, days out of work and so on.For example, the estimated mean cost per patient per year in 2017 for USA and Europe were USD 3100 and USD 1900, respectively. 20In Thailand, an upper-middle income country in the APR, the average annual cost per patient was USD 599 for the year 2011. 21These economic estimates are lower for the LMIC in the region, with a retrospective cost analysis in AIRIAP showing a cost of below USD 300 in APR LMIC out of the countries surveyed (Figure 2).Further, this cost analysis represented 13% of per-capita GDP for the entire region, where the individual cost burdens were higher for Vietnam (35%) and Philippines (21%). 22

RISK FACTORS OF ASTHMA
Our review found that studies conducted in APR LMIC reported a range of risk factors in relation to asthma (Figure 3).These factors include pre-and post-natal, environmental, lifestyle, individual, and genetics, as outlined below.

Pre-natal and Post-natal Factors
Exposures during pregnancy have been associated with childhood asthma in APR LMIC.For example, it has been reported in Pakistan that maternal respiratory symptoms such as nocturnal cough and wheezing are associated with an almost 3-fold increased odds of childhood asthma. 23hese maternal symptoms may indicate underlying asthma.Asthma exacerbations during pregnancy can interfere with foetal development and oxygen delivery, and subsequently increase the risk of respiratory health problems for the child. 24The same study found that exposure to goats during pregnancy was associated with an increased risk of childhood asthma.Similarly, the ISAAC study showed that exposure to farm animals during pregnancy can increase the risk of asthma in children living in non-affluent countries. 25In farming environments, there is high endotoxin exposure, which has been associated with airway symptoms and bronchial hyper-responsiveness. 26 The ISAAC study finding was limited to non-affluent countries, potentially because smallscale livestock farming is more common in these countries, where the type of exposure may also differ from that of animal farms in affluent countries.
A meta-analysis of four studies conducted in Asian countries found that exclusive breastfeeding was not associated with overall asthma risk. 27However, in Pakistan, breastfeeding for at least 2 years was associated with a 1.77-fold increased odds of asthma, but if this duration was shorter, that is, a year or less, exclusive breast feeding would have a protective effect against childhood asthma. 28The discrepancy in study findings could be related to differences in study design, population, biological variability in human milk and/or breastfeeding practices.A systematic review of 42 articles worldwide, selected with stringent inclusion criteria, concluded that exclusive breast feeding has a protective role in developing asthma among children aged 5-18 years. 29Besides breastfeeding, a meta-analysis of the Asian populations by Sio and colleagues also showed that low birthweight of <2.5 kg (n = 6 studies), pre-term birth of ≤ 37 weeks (n = 6 studies) and childbirth by caesarean section (n = 8 studies) can increase the overall risk of asthma. 27Low birthweight and pre-term birth are both related to impaired infant lung and immune system development which increases the propensity for asthma. 30,31ncreased risk of asthma observed in children born by caesarean section may be related to the hygiene hypothesis, 32 which indicates that lack of contact with the mother's bacteria can increase the risk of asthma, because these bacteria are required for the development of the immune system of the new-born.F I G U R E 4 Sri Lankan traditional cooking stove in rural areas using firewood, coconut husks and coconut shells as fuel.

Environmental Factors
4][35] A similar asthma risk was observed in Pakistan for women living in households with poorly ventilated kitchens. 36Burning of solid fuels in poorly ventilated kitchens results in high exposures to toxic pollutants that are detrimental to health (Figure 4).The typical range of mean carbon monoxide concentrations in biomass-fuelled homes is 2-50 ppm but it can go up to 500 ppm during cooking. 37This is substantially higher than the Environmental Protective Agency safety standard of <9 ppm.
Further to the indoor air pollution as mentioned above, people living in LMIC are often exposed to high levels of outdoor air pollution, which may have a direct inflammatory and irritant effect on the airway epithelium and neruoreceptors. 38The meta-analysis by Sio et al. 27 demonstrated that PM 10 increased the overall risk of asthma by 1.22-fold (n = 8 studies) in Asian countries.In India and Indonesia, frequent passage of trucks near residential houses has been associated with a 1.7 times higher risk of wheezing in children. 39,40eroallergens such as pollen, mould/fungi, house dust mites, pets and cockroach particles are important risk factors of asthma.Increased allergen exposure can lead to sensitisation, and constant re-exposure to allergens in sensitized individuals can induce asthma and other allergic conditions. 41In Asian countries, the presence of mould (n = 10 studies), mould odour (n = 10 studies) and cockroach (n = 6 studies) increased the overall risk of asthma by 1.43-fold, 1.73-fold and 1.44-fold, respectively. 27

Lifestyle/Individual Factors
In Asian countries, random-effect meta-analysis have indicated that males have a 1.3-fold higher risk of asthma (n = 73 studies). 27Similar findings were observed in studies performed in Pakistan. 36In India and Pakistan, the younger age groups tend to be more susceptible to asthma than older age groups, 35,36,42 potentially due to higher exposure to environmental, pre-and post-natal factors as mentioned above. 35,36nhealthy lifestyles such as poor diet, obesity and sedentary behaviours have been linked to asthma in developing regions.In Asian countries, meta-analysis showed that obesity (>30 kg/m 2 ) was associated with an overall increased risk of asthma by 2.02-fold (n = 8 studies). 27Sedentary behaviours such as increased TV watching, and reduced hours of physical activity have found to be correlated with asthma risk. 43However, it is still unclear whether asthma predisposes an individual to obesity, if obesity confounds asthma diagnosis, or that both asthma and obesity simply co-occur or interact.Obese individuals with asthma are more likely to have Th1-skewed inflammatory responses, which is in part mediated by insulin resistance, systemic inflammation and/or alterations in lipid metabolism. 44n the other hand, poor diet such as fast-food consumption was associated with increased risk of current wheeze, while fruit intake of more than twice a week was protective. 39,40Higher intake of polyunsaturated fatty acids may provoke Th2-related asthma by increasing the production pro-inflammatory mediators. 45In Bangladesh, stunting was a prominent risk factor for wheezing in children living in rural areas, suggesting that poor nutrition can result in detrimental health effects. 46Further studies have postulated that low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels seen in stunted children may have a role in increasing asthma risk. 47ultiple studies have indicated that smoking is a major risk factor for asthma worldwide, including APR LMIC.In Asian countries, passive cigarette smoke exposure and cigarette smoking were associated with an overall increased risk of asthma by 1.44-fold (n = 21 studies) and 1.66-fold (n = 28). 27In India, the risk of asthma was higher for smokers in both men (OR 1.3) and women (OR 1.7), but coupled with biomass and solid fuel exposure, the impact was greater in women. 33In children, the risk of wheezing was higher for those with mothers and/or fathers who smoked and this finding has been consistently reported in India and Mongolia. 39,48It is believed that cigarette smoke triggers synergistic or additive remodelling and inflammatory responses in the airways, increasing susceptibility to respiratory conditions. 49MIC with lower socio-economic status (SES) were consistently reported to have higher prevalence of asthma than those with higher SES, most likely due to limited access to healthcare, poor housing conditions, and lower health literacy (Figure 5). 35SES measures that have been studied in the APR include education level, employment status and property ownership. 35,50,51Further, childhood viral respiratory infections in poor SES would increase the risk of asthma by inducing TH2-based immune responses. 52,53

Genetics/Ethnicity
In Asian countries, having a family history of asthma increased the asthma risk by 4.66-fold (n = 36 studies). 27imilarly, an increased risk was also observed for other allergic diseases, such as allergic rhinitis, eczema and atopy.This finding is supported by evidence found in Pakistan, where asthma was found to be more prevalent in those of Sindhi ethnicity. 36Polymorphism of multiple genes have been identified as risk factors for asthma.This includes IL-17 G-152A polymorphism (rs2275913), SNPs Rs2289276 and Rs2289278 in the TSLP, Hap3 (CAC) and Hap4 (CAG) haplotypes. 54 systematic review performed in LMIC demonstrated that environmental exposures could cause epigenetic dysregulation of the histone deacetylase (HDAC) and histone acetyltransferase gene families, and deoxyribonucleic acid methylation.55 In turn, these epigenetic changes can increase the risk of chronic respiratory diseases such as asthma.

CHALLENGES IN ASTHMA MANAGEMENT
Our review also found that asthma management in APR LMIC poses its own challenges in the socio-cultural, genetic, economic and environmental domains.

Asthma Control and Socio-cultural Factors
Recognize Asthma and LInk to Symptoms and Experience Asia study REALIZE-Asia studied subjective asthma control in eight Asian countries, as per Global Initiative for Asthma (GINA) asthma control definition. 56Five attitudinal-control clusters were defined among 2467 patients with physiciandiagnosed asthma, and it was revealed that over half fell into clusters with poor disease control: namely adrift and poorly controlled (Lost, 14%), tolerating with poor control (Endurers, 29%) and worried with multiple symptoms (Worriers, 11%).
The multi-national AIRIAP study in 2000, which included several LMIC, found grossly inadequate asthma control among physician-diagnosed asthmatics with 36.5% and 26.5% reporting absence form school and work, respectively, due to asthma symptoms in the preceding 12 months. 19Hospital admissions or emergency visits were required by two out of every five respondents, with one-third of severe asthmatics having the perception that their disease is well controlled.Unfortunately, this study did not provide country-specific details.
Deficiency in asthma self-management using 'personalised asthma action plan' is thought to result in poor asthma control and frequent unscheduled hospital visits among Asian populations.A recent systematic review identified socio-cultural factors, poor understanding and knowledge on asthma and related factors and language barriers as key contributors hindering use of personalized asthma action plans among Asians. 57lternative and herbal medicine use is also common in many Asian cultures, particularly LMIC, which may hamper a diagnosis of asthma and lead to non-adherence of maintenance therapy.Chinese and Indian herbal treatment are practiced in many LMIC in the region.It has been noted that majority of Indian asthmatic patients try alternative medicine to 'cure' their asthma, which includes 'saintly therapy', herbal medicine, fish therapy and acupuncture. 58

Perceptions on Asthma Treatment, Availability and Affordability
The AIRIAP study further revealed a high use of relievers and low use of preventers among asthmatics of all severity stages in the APR in 2000. 19Use of inhaled corticosteroids (ICS) ranged from 12% to 18% among persistent asthmatics (Figure 6), where only 23% realized inflammation was the underlying cause for asthma and 30% believed risks of inhaled corticosteroids (ICS; the mainstay of asthma management) outweighed the benefits.This 'steroid phobia' and treatment non-adherence is commonly seen in APR LMIC. 59A literature review on barriers of asthma management among children of South Asian origin living in F I G U R E 5 Overpopulated and poorly conditioned line housing schemes are not uncommon in many developing countries in the Asia-Pacific region (Picture depicts Tamil community in Sri Lanka's Estate Sector, that is, tea and rubber plantations).developed countries identified stigmatization as a key barrier leading to non-acceptance and denial of asthma diagnosis and non-adherence to medication, confirming that sociocultural factors hindered optimal asthma control. 60nderdeveloped national health services and limitations in free availability of asthma medications are major factors leading to treatment non-adherence in many LMICs.Among 300 inhaler users, poor adherence to inhalers was noted among 81% with 68% reporting financial reasons as a barrier to proper inhaler adherence. 61Illustrative of this finding, in 2007 1 month of maintenance asthma treatment from the private sector cost 1.3, 5.4, 2.5 and 2.3 days' wages for a lowest-paid government worker in Bangladesh, Nepal, Pakistan and Sri Lanka, respectively. 8imited budgetary allocations to preventive healthcare compared to the curative sector in many developing countries has led to poor availability of asthma diagnostics, medication, and support care, including spirometry services, allergic testing and asthma care nurses.Newer inhaled molecules and biologics are not registered in many LMICs.Diagnosis and management of severe eosinophilic asthma is grossly deficient in many APR LMIC due to lack of reference centres for severe asthma. 62In Sri Lanka, formoterolbased inhaler combinations, though available in the private sector, are not yet freely available to asthmatics registered at free Government clinics.In a survey of physicians from eight APR countries, use of either a peak-flow meter or a spirometer to monitor symptoms among asthmatic children was significantly lower in LMIC, for example, 8.1% in Sri Lanka compared to 52.0% in Australia. 63The survey also revealed that 97.6% of physicians in Indonesia never or seldom used spirometry in disease monitoring.

Asthma Heterogeneity and Climatic Challenges
There is growing evidence that asthma in the APR may have different genotypes and phenotypes, presenting another challenge in asthma treatment in the region.Phenotypic cluster analysis among over 600 adult asthmatics in Singapore revealed three distinct phenotypes; namely Chinese females with late-onset asthma who had best prognosis, multi-ethnic groups with atopy, and non-Chinese females with obesity who had the worst prognosis. 64Similar clustering had identified six asthma phenotypes in Japanese adults, which are linked to functional CCL5 and ADRB2 genotypes with possible distinct pathophysiology. 65This heterogeneity of asthma in Asians provided further unique challenges in phenotyping, risk stratification and management of asthma in the region.Even though this evidence on asthma heterogeneity has come from affluent APR countries, the related diagnostic and treatment challenges are greater for LMIC in the region.It has been identified that age-related 'second peak' in asthma, a poorly understood phenomenon, is more prevalent in Asia. 66This is potentially related to multiple factors including smoking, air pollution, low socio-economic status, obesity and exposure to non-conventional allergens.
Rapid urbanization and economic growth in many parts of Asia has led to increased outdoor air pollution due to vehicle and industrial exhausts from fossil fuel burning, with some major cities of China and India being the worst hit 67 (Figure 7).The rise in particulate matter (PM) and polluted gases in outdoor air has led to an increase in asthma prevalence and hospital admissions longitudinally. 68Transboundary air pollution, due to regional wind circulation, has also been identified as an important cause of ambient air quality F I G U R E 6 Over-reliance on reliever medication and under-usage of inhaled steroids among asthmatics based on the AIRIAP study which included data from 8 countries, that is, Hong Kong, Taiwan, China, Malaysia, Philippines, Korea, Singapore and Vietnam. 19 deterioration in many Asian countries.In South Korea, Asian dust storms originating in Central Asian deserts was noted to increase the number of asthma treatment visits in Spring by a significant 22%, with a parallel rise in PM 10 concentration. 69Similarly, in Sri Lanka high ambient air pollution during its dry months coupled with circulating dry wind from the South Asian subcontinent resulted in a significant 0.63% rise in asthma hospitalizations and a proportionate rise in PM 2.5 and PM 10.

Other Challenges
Many APR LMIC operate within restricted national health budgets.Here, asthma may not be prioritized over other non-communicable disease, despite its rising prevalence and substantial disease burden.Low doctor-to-patient ratios, unequal distribution of health care facilities, lack of proper primary care services with proper patient registrations, lack of coordination between the primary physician and specialists with proper referral and back-referral system may all contribute towards failure of continuity of asthma care.In an over-stretched health system, both patient and physician may not look beyond symptomatic control, and patient motivation to continue maintenance treatment would be low in the absence of a dedicated support from a healthcare team, including asthma nurses, respiratory physiotherapists and health educators.
Unreliable medicine supply chain, even in countries with free health services to their citizens, has led to disruption of long-term asthma management.Lack of a national insurance scheme or uniform private health insurance in LMIC, including in the APR, has resulted in many asthmatics discontinuing maintenance therapy, especially amidst the regional economic hardships.Many physicians find it difficult to abide by the standard asthma treatment protocols for the same reasons.Furthermore, it is not uncommon for some primary physicians to be unaware of updated management protocols due to lack of in-service training and revalidation programmes in health systems in some LMIC.
A major challenge in asthma care in APR LMIC is the management of severe asthma.Clinical data from wellconducted epidemiological studies on severe asthma and allergy are usually lacking in these countries.Diagnosis of severe asthma would require advanced allergic testing, which is commonly absent, and most LMIC do not have access to newer biologic treatments.Establishment of even a few specialized centres for respiratory allergy and severe asthma in each APR LMIC country would help to bridge this gap.

CONCLUSIVE SUMMARY
The main findings and conclusions of this review are summarized in Table 1.Asthma prevalence in low-and LMIC is known to be generally lower compared to high-income countries globally.However, asthma burden is substantially greater in low and LMIC.The majority of asthma-related deaths occur in these countries, and they have higher absence from school or work and emergency visits.This remains especially true in APR LMIC, where high population density, financial instability and diverse socio-cultural background only increase the challenges of effectively managing asthma.In some LMIC, treatment non-adherence can be as high as 80% with financial barriers accounting for over 60% of such cases.
Studies conducted in APR LMIC have reported a range of risk factors in relation to asthma, including pre-and post-natal factors, environmental considerations, lifestyle measures, individual features, and genetics.Some of these factors are unique to the APR (e.g., second peak phenotype, transboundary air pollution, socio-cultural beliefs and practices) emphasizing the need for region-specific preventive, T A B L E 1 Main findings and conclusions of this review.

Asthma prevalence and disease burden
It is difficult to estimate asthma prevalence in various countries because different questionnaires have been used to ascertain asthma symptoms, but the World Health Survey (WHS) showed that Asian countries, particularly Vietnam and China, were among the few countries with lowest adult prevalence of asthma. 11,12This could be due to factors such as lower rates of atopy and higher exposure to microbes.However, several studies have shown that asthma burden (mortality and morbidity) was higher in LMIC compared to high-income countries. 16,17nerally, the prevalence of asthma in low and LMIC has been reported to be lower compared to high-income countries, but the burden of asthma is substantially greater.

Risk factors of asthma
• Pre-natal: Maternal respiratory symptoms and exposure to farm animals during pregnancy have been associated with increased risk of childhood asthma. 23,258][29] However, low birthweight, pre-term birth and childbirth by caesarean section have shown to increase the overall risk of asthma. 2736][39][40][41] • Lifestyle/individual factors: Males, younger age groups, lower socioeconomic status and unhealthy lifestyles (e.g., smoking, poor diet, obesity, sedentary behaviours) have all been linked to asthma. 27,33,35,36,39,40,42,46,48 Genetics/ethnicity: Few studies have indicated that family history of asthma, certain genes and epigenetic changes can increase the risk of asthma. 35,50,51wide range of asthma risk factors have been reported in APR LMIC, such as pre-and post-natal environmental, lifestyle/individual, and genetics.

Challenges in asthma management
• Asthma control and socio-cultural factors: Studies have demonstrated that asthma is poorly controlled in APR LMIC. 19,56Poor understanding and knowledge on asthma, language barriers and alternative medicine have shown to be key contributors to poor asthma control. 57,58 Perceptions on asthma treatment, availability and affordability: Stigmatization and steroid phobia can lead to non-acceptance of asthma diagnosis and non-adherence to medications. 59,605][66] Rapid urbanization and economic growth can lead to increased air pollution exposure, contributing to the worsening of asthma burden in APR LMICs. 68 diagnostic and therapeutic approaches for effective and uniform asthma prevention and control in the region.
Long-term studies of the natural history of asthma may help understand country-specific risk factors; an effort which would require investment by global funding bodies.Furthermore, the APR is highly diverse where populations with significant variation in genetic backgrounds live in same environments and populations with similar genetic backgrounds live in different environments.This makes the ideal environment for epidemiological and gene-environment interaction studies.Convincing funding organizations of the importance of such studies is a critical step to accelerate such comprehensive research in LMIC more broadly.The low and inequitable distribution of quality preventive and curative health care, a lack of advanced diagnostic measures, non-availability and non-affordability of novel therapeutics, cultural beliefs and practices, and diverse disease phenotypes make it more challenging to achieve optimal asthma control in the region.We call for the development of a region-specific blueprint for action to mitigate this challenging situation, and to help reduce the burden of asthma in APR LMIC.A proposed framework of an APR-specific blueprint is outlined in Table 2.

Establishing regional collaborations
To conduct country-specific and regional collaborations in all above activities Participation and contributions at scientific sessions of regional societies

F I G U R E 1
Prevalence of symptoms of asthma in the preceding 12 months among persons aged 18-45 years in 70 countries, World Health Survey 2002-2003.12

F I G U R E 3
Risk factors of asthma in developing countries in the Asia-Pacific region.
5 ambient air pollution in Asia in March 2023.67Reproduced with permission from www.berkeleyearth.org.
-70• Other challenges: Many APR LMIC operate within restricted national health budgets, and there is low doctor-to-patient ratios, unequal distribution of health care facilities and lack of proper primary care services.It has also been shown that there is unreliable medicine supply chain, lack of national insurance schemes and restricted access to newer biologic treatments.Proposed framework of an Asia-Pacific region-specific blueprint for action to mitigate challenges in asthma.