Advancing Mental Healthcare for Individuals with Cystic Fibrosis in Low- and Middle-Income Countries

Advancing Mental Healthcare for Individuals with Cystic Fibrosis in Low- and Middle-Income Countries | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 1 October 2025 V1 Latest version Share on Advancing Mental Healthcare for Individuals with Cystic Fibrosis in Low- and Middle-Income Countries Authors : Alexandra L. Quittner [email protected] , Sonia Graziano 0000-0002-7478-8414 , Minu P. Mohan , and Beth Smith Authors Info & Affiliations https://doi.org/10.22541/au.175928769.92475700/v1 Published Pediatric Pulmonology Version of record Peer review timeline 254 views 136 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Cystic fibrosis (CF) presents significant challenges for both patients and their families. However, the mental health needs of persons with cystic fibrosis (PWCF) in low- and middle-income countries (LMICs) remain underexplored. Limited resources, fragmented healthcare systems, and inequities in access to essential CF treatments often compound psychological stressors such as depression, anxiety, and caregiver burden. This review examines existing literature on the mental health and psychosocial challenges of PWCF and their families in LMICs, highlighting the intersection between inadequate physical healthcare and poor mental health outcomes. Findings suggest that disparities in access to diagnostic services, medications, and multidisciplinary care exacerbate emotional distress, leading to poorer quality of life compared to counterparts in high-income countries. Families often experience financial strain, social isolation, and limited psychosocial support, which further magnify mental health challenges. Addressing these inequities requires integrating mental health care into routine CF management, even in resource-limited settings. Low-cost strategies such as regular mental health screening, translating available CF-specific mental health resources, and the provision of brief interventions via digital and internet-based technologies show promise for sustainable implementation. The review underscores the need for increased research in LMIC contexts and the development of scalable interventions that address both physical and psychological dimensions of CF. Ensuring parity with high-income countries demands recognition of mental health as a core component of CF care. Introduction Recent advances in the treatment of cystic fibrosis (CF) have transformed this genetic condition from a life-shortening disease, with a substantial treatment burden, into a chronic condition that can be managed. The development of highly effective modulators has, for the first time, addressed the underlying genetic defect in the cystic fibrosis transmembrane regulator (CFTR) protein that causes debilitating pulmonary and digestive symptoms. New gene therapy treatments are in clinical trials, with the strong possibility of a cure in the next 10 years. [1] Despite this remarkable success, most low and middle-income countries (LMICs) have limited access to these new medications. In fact, many LMICs do not have access to the standard treatments for CF , such as recombinant human deoxyribonuclease (rhDNase) or inhaled antibiotics. [2] A recent analysis of the European Cystic Fibrosis Registry (ECFSPR) based on gross national income per capita, divided into low-income, middle-income, and high-income, examined survival from 2013-2017 and 2018-2022. People with CF (PWCF) in low-income countries had significantly lower median survival age, lower lung function, and a higher prevalence of Pseudomonas aeruginosa (PA). Modeling results indicated that avoiding underweight status and PA would increase survival by 42 years; access to modulators would add 15-29 years to survival, depending on nutrition and infection status. [3] In addition to worse long-term survival, children with CF and their families in LMICs face a burdensome daily treatment regimen, frequent exacerbations and hospitalizations, stressful medical procedures, and earlier mortality. As might be expected, high rates of depression and anxiety have been reported in many of these countries for both children and adolescents with CF and their parents. Negative consequences of these mental health symptoms include worse adherence to prescribed treatments, missed clinic visits, more frequent pulmonary exacerbations and hospitalizations, and earlier mortality. [4] The key theme of this review is: there is no health without mental health (Figure 1). Despite limited access to advanced treatments for CF, we can address the psychosocial challenges these patients and their families face to improve their quality of life. [5] A recent systematic review and meta-analysis documented the global burden of depression and anxiety among PWCF. [6] Despite their goal to represent a “global” perspective, most studies were conducted in North America and Europe. The review included 26 studies conducted on these two continents, representing 9,766 PWCF. Overall pooled prevalence of depression and anxiety, corrected for bias, was 23.6% in North America and 26.8% in Europe. Just over 10 years ago, The International Depression/Anxiety Epidemiological Study (TIDES) was published, screening depression and anxiety in 6,088 adolescents and adults with CF and 4,102 parent caregivers in 9 countries, finding rates of depression and anxiety 2-3 times higher than in the general population. [7] Turkey, an upper-middle-income country, was included in this prevalence study; however, their rates were much higher than those of its European counterparts, with 54% of PWCF reporting clinically elevated depression and 29% elevated anxiety. A follow-up analysis of the TIDES study showed that a single positive depression screen among PWCF in the US was associated with a doubling of mortality within 5 years. Both the TIDES study and this recent meta-analysis concluded that these psychological symptoms are very common, should be viewed as normal responses to an abnormal situation, and should be proactively addressed with routine, standardized screening and psychological support. [8] The main purpose of this review is to identify the psychosocial challenges faced by children, adolescents, and adults with CF and their families, and provide recommendations to facilitate the integration of mental health into CF care. We conducted a search of the published literature using PubMed, Psychlit, Medline, Google Scholar, and published conference abstracts relevant to CF. The literature is sparse and not sufficient, at this point, to undergo a systematic review. We will highlight how current inequalities and health disparities in physical care in LMICs interact with the goals of advancing mental health care (Table 1). Mental Health Challenges in LMICs Need for early diagnosis and newborn screening . Across Africa, the Middle East, Asia, and Latin America, infants born with CF face a substantial delay in their diagnosis (see Chapter 2 in this Special Issue). The lack of newborn screening in most LMICs leads to years of delay in identifying the cause of the infant’s symptoms, prevents early genotyping, increases the risks of nutritional failure, and is correlated with worse health outcomes. It is estimated that 82% of the world’s undiagnosed PWCF live in LMICs. [9] The psychological impact of this delay includes increased parental stress and depression as the family searches for the cause and has little information to guide early interventions, including the use of pancreatic enzymes and increased calorie intake. This can lead to incorrect attributions for the cause—potentially blaming parents for the child’s failure to thrive. [10,11,12] This diagnostic journey has been characterized as an “emotional roller coaster” for parents and can lead to marital strain, as partners may blame one another, and heightened stress and anger among extended family. Importantly, the lack of diagnosis delays the implementation of critical treatments, which contribute to the lack of hope and increasing despair. Need for updated education. In the absence of a clear understanding of the genetic cause of CF and parents’ carrier status, parents and family members may resort to blaming each other, most often the mother. [13,14,15] It may also result in a lack of family planning, having multiple children with CF, and thus, a greater caregiving burden. In addition, the long-standing cultural and religious traditions of arranged marriages are quite common, and a genetic disease diagnosed in one child may affect the other siblings’ marriageability. There is also a great deal of misinformation, including the notion that CF is a contagious, rather than genetic, disease. Families may experience social isolation, a desire to “hide” the child with CF from the larger community, and ostracization from the extended family. Limited access to CF medications. In many LMICs, there is no access to standard CF medications offered in the US, Canada, Australia, Europe, and parts of Latin America (e.g., inhaled tobramycin, rhDnase). [15,16] For example, there is no reimbursement for standard therapies in India or in poorer countries in the Middle East (e.g., Egypt, Jordan). In India, families rely on rare-disease grants and crowdfunding. The Middle East CF Association advocates for free access to “essential drugs and equipment,” but the reimbursement process for these is unclear. [17] Lack of access to standard therapies leads to increased parental stress, greater economic burden for families, and a more rapid worsening of disease for the young child. Without these treatments, children will have more frequent exacerbations, hospitalizations, greater morbidity, and much earlier mortality. In many of these countries, average life expectancy is middle childhood or adolescence. In India, median life expectancy (2023) is just 5 years, in the Middle East, median survival ranges from 10 to 20 years, and in Africa, there is little published data, but many patients die in childhood. Even though Mexico is on the same continent as the US, life expectancy for children with CF in Mexico is only 10 years. [13] This is in stark contrast to current life expectancies in Western countries, which range from 45 to 60 years. As noted by the psychologist in Jordan, many of these mothers have already lost a child to CF; thus, parental grief and loss are an integral part of caring for a child with CF in these countries. Limited to no access to modulators. Genetic modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (Alyftek Ⓡ ), have been transformative, reducing respiratory symptoms and infection, increasing weight gain and growth, increasing fertility, and substantially lengthening life span [18, 19]. However, they are extremely expensive, with ETI costing approximately $322,000 per year [20] and Alyftrek Ⓡ costing $370,000 per year [20] . The cost of these life-saving medications has dramatically increased the health disparities experienced by PWCF. According to Guo and colleagues, [21] ETI is reimbursed in just 5 LMIC countries (Egypt, India, Kenya, Nepal, Uganda), leaving 51 predominantly LMIC countries with no access. However, recent publications from Egypt and India indicate that these modulators are not available or are available to a limited subset of PWCF. [2,22, 23] In 2024, the patent holder of ETI, Vertex Pharmaceuticals, announced a novel donation program in partnership with Direct Relief to provide ETI in 12 LMICs: Cote d’Ivoire, Egypt, El Salvador, Honduras, Kenya, Lebanon, Nepal, Sri Lanka, Tanzania, Tunisia, Uganda, and Ukraine, with expansions into India and Pakistan. The estimated number of people diagnosed with CF in these countries is 1,647, rising to 3,139 with the inclusion of India and Pakistan. This translates into coverage for about 19.5% of the CF population in LMICs. Although this is a very positive step, there are still many barriers limiting access: 1) need for genetic analysis or newborn screening to determine eligibility; 2) large number of genotypes which have not yet been identified; 3) approval of the medication by each country’s regulatory body; 4) requirements in some countries to pay a lawyer to sue the government for access (e.g., Chile); and 5) the use of generic formulations, which may need to be enhanced with clarithromycin. [9,23] There is no published data on how many children with CF have received ETI through this donation program. It is difficult to imagine how a parent of a child with CF might feel knowing that there is a life-saving medication available for their child, which they cannot access or afford. This creates a growing divide between the “haves and have-nots” of CF care based on geographical location, which can lead to frustration, demoralization, and depression. [24] Specific religious and cultural barriers. In most LMICs, there are religious or cultural barriers that affect the management of CF. In African and Middle Eastern countries, for example, there are high rates of consanguinity (intermarriage among close relatives such as cousins), which magnify the genetic risk for carriers of the defective CF gene (Figure 2). Importantly, these parents do not know they are carriers until they have a child with CF. A recent epidemiological study of 120 children with CF in Egypt reported a rate of 51% consanguinity, [2] and in a recent study in Jordan, it was 27.5%. Lack of mental health assessment and treatment. Following publication of the TIDES study [7] , the European Cystic Fibrosis Society (ECFS) and CF Foundation sponsored development of international guidelines for mental health [8] , which recommend annual screening of depression and anxiety using brief, well-validated measures, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7). The PHQ-9 and GAD-7 are free, available in up to 80 languages (Table 2), and can be completed in 5 minutes. The key to implementation is to use the same standardized screening measures across countries, facilitating comparisons of rates of depression and anxiety, and evaluations of the efficacy of psychological interventions. In most European countries and the US, mental health screening has been integrated into standard of care for CF [28]. In the US, CF teams have a Mental Health Coordinator (e.g., social worker, psychologist) who administers the instruments, scores them, and discusses the results. The discussion of results is critically important. A recent survey conducted in Europe and the US with PWCF and caregivers suggested that mental health screening is itself an intervention . [29] It raises awareness, provides an opportunity to discuss how you are functioning and feeling, and enables patients and families to access psychological support. PWCF in LMICs report high rates of depression and anxiety; however, very few of these countries have any standardized mental health screening or intervention programs. There are also few trained mental health professionals working in CF clinics, a lack of standardized screening tools, and limited psychological support. Fortunately, the recommended screening tools have been translated into many of the LMIC languages; with a brief training, nurses and other members of the CF team can learn to administer these screening tools and provide feedback. ECFS TWINNING PROJECT: A MODEL FOR IMPLEMENTATION OF MENTAL HEALTH INITIATIVES The European Cystic Fibrosis Society (ECFS) Twinning Project was implemented in cooperation with ECFS and CF Europe (CFE) in 2020 to address disparities in CF care across Europe. This project addresses the need to improve the quality of care in regions where CF treatment centers lack sufficient resources and expertise. It establishes partnerships between well-functioning ”mentor” centers with a track record of excellence and collaboration with “mentees”. The goals are to exchange knowledge and best practices, share resources, and guide implementation of new approaches to CF care. The mentee site is typically just beginning to implement the CF Standards of Care [28] with the aim of improving clinical outcomes using the guidance, advice, and collaboration of a well-established CF center. The Twinning Project is aimed at enhancing clinical capacity in countries with fewer resources. Over time, the project has expanded, incorporating new centers and patient organizations, striving to improve clinical outcomes for PWCF throughout Europe. In the expansion of the Twinning Project, patient organizations are now included to: 1) help identify unmet needs (e.g., adult care, specialist training); 2) support communication and planning at the mentee sites; 3) and organize team meetings to facilitate peer guidance. As part of the Twinning and Expansion Project, the Southeast European CF Conference was held in Prishtina, Kosovo, in 2025 to foster regional collaboration. This event brought together over 300 healthcare professionals, patient organizations, and experts to share knowledge, discuss challenges, and promote CF care in the region. A Real-World Example of a Twinning Pair: Italy (Mentor) and Albania (Mentee) Context. Albania is an LMIC with limited healthcare resources and no specialized CF Center. They lack access to diagnostic tools, CF medications, and dedicated multidisciplinary care teams. Albania’s population is approximately 2.4 million, with an incidence of 1:3300 live births, and 7-8 new CF cases per year. M ean age at diagnosis is approximately 0.4 years, with neonatal screening available only in private hospitals. Early diagnosis can be challenging due to limited newborn screening which delays in diagnosis and treatment, impacting long-term health outcomes. CF care in Albania faces significant challenges but has also shown substantial progress. Since 2024, thanks to a five-year ECFS-Patient Registry grant, sweat tests are now conducted at the Pulmonology Service by trained staff. Genetic testing is also performed and includes a limited panel SNaPshot assay of 11 known CF-causing variants. There is no national CF registry in Albania; however, in 2017, Albania joined the ECFS Patient Registry (ECFS-PR) to gather more accurate prevalence data. In 2024, access to CF–related medications and devices was variable. Certain essential oral treatments, including macrolides, proton pump inhibitors, and pancreatic enzymes, were fully reimbursed. Inhaled bronchodilators and some inhaled antibiotics (e.g., Colistin) were also accessible, whereas others—including hypertonic saline, rhDNase, Mannitol, and Tobramycin—are not currently reimbursed. Oral antibiotics are only partially reimbursed, and modulators are not yet approved or available. Nutritional supplements and common CF devices, such as nebulizers and positive expiratory pressure (PEP) masks, are not reimbursed. Only two CF units are currently established in this country, both of which are in the capital, Tirana: 1. Pediatric Unit at the University Hospital Center Mother Teresa, Department of Pediatrics. Five beds are specifically allocated for PWCF, with one clinic room for outpatient visits. A multidisciplinary CF team is not available. As of 2023, 105 children with CF were registered, although the actual number is likely higher. Recently, many patients left Albania to seek better care, making the data highly variable.2. Adult Center of Cystic Fibrosis, University Lung Department, Regional Hospital of Tirana Shefqet Ndroqi. This center, established in 2020, is dedicated to the care of PWCF and tuberculosis. There are 27 adults currently registered; however, only 15 are regularly followed. To date, only six patients have been included in the national registry, as many are followed in other countries. The multidisciplinary team consists of a pulmonologist, a nurse, and a physiotherapist; however, a dedicated psychologist or psychiatrist is not available. The Albanian healthcare system has made progress in raising awareness of CF; however, access to comprehensive care remains a challenge, especially for those living outside major cities. CF care is largely centralized in the capital; however, these centers often face shortages of modern medical equipment, medications, and specialized healthcare professionals, which reduces the quality of care. Many families rely on external support, including international organizations or private healthcare options, to access CF treatments. The Albanian CF community is advocating for better facilities, more trained specialists, and improved access to treatments to improve quality of life for PWCF. In June 2025, the Albanian Patient and Family Association was officially registered. The association focuses on the following topics: 1. Raising Awareness : Educating the public, healthcare professionals, and policymakers about CF. 2. Supporting Patients and Families: Providing support and resources to PWCF and their families. 3. Advocacy: Working to improve access to healthcare, better treatments, and a higher quality of life. 4. Collaboration : Partnering with international organizations, healthcare professionals, and researchers to share knowledge and improve care for PWCF. Visit to Tirana, Albania by the Mentor Site . In 2024, the multidisciplinary CF team from Bambino Gesù Children’s Hospital in Rome traveled to Tirana, Albania. The team included a pediatrician, a psychologist, a physiotherapist, and a nurse. The four-day visit was preceded by two virtual meetings attended by the Italian team and the directors of the two Albanian centers. For the mentoring country, this was an opportunity to gain a deeper understanding of the needs, challenges, and resources in Albania. During the visit to Albania, a long-term relationship was established between the Albanian and Italian Parent. Next, the Albanian pulmonologist began participating virtually in clinical cases conducted by the mentor center. The project’s lead pulmonologist visited the Italian center in Rome in 2025, and in 2026, a visit to Italy by the multidisciplinary team was planned. Implementation of Mental Health in the Twinning of Albania and Italy During the visit to Albania, the psychologist from the Italian team shared information and materials to strengthen psychosocial care; these activities are summarized in Table 3. This collaboration between Italy and Albania has been a tremendous success, and the CF team in Albania is excited to incorporate mental health assessment and treatment into their CF care. This twinning project serves as a model for integrating mental health into the management of CF in other global regions, such as Africa, the Middle East, and Latin America, discussed later in this review. Several other twinning pairs are also addressing mental health. Africa There is a notable lack of information on CF in populations of the African continent. What is known from the African continent is mainly based on data from South Africa (SA) and populations of European descent, despite early reports of CF in black Africans dating back to 1959. Since then, studies from SA [30] , Rwanda [31] , and Sudan [32] have described CF in children of African ancestry, [33] and CF registries have found immigrants from Africa diagnosed with CF in the UK, US, and France [34] . The prevalence of CF in North Africa is likely underestimated, as newborn screening and sweat tests are rarely performed, and many clinicians do not consider CF a probable diagnosis. [35] Further, a diagnosis of CF in Africa may be overshadowed by more rampant illnesses such as protein-energy malnutrition, chronic pulmonary infections, and human immunodeficiency virus. When diagnosed, PWCF born in Africa face a higher risk and can expect to live approximately half as long as their European counterparts. The absence of an effective and comprehensive public health strategy for CF in African countries is mainly responsible for this disparity. [36] There is a similar paucity of mental health data in PWCF from the African continent, again with most available data from SA, which is categorized as an upper-middle-income country. Further, many PWCF in SA are eligible for CFTR modulator therapy, [17] so these findings are unlikely to generalize to other parts of the African continent. South Africa launched its CF registry in 2018, adopting similar data collection methods as the European CF registry. There is concern, however, that people with black African ancestry, who form most of the SA population, are underrepresented in the SA CF registry, raising concern that CF is being missed or underdiagnosed in the majority of South Africans .[15] Data from this registry shows disparities between racial groups still exist in SA, with increased risk of mortality observed in young children who were not white [37] . The registry reports mental health complications, with the 2023 registry reporting 13 (4.9%) children under 18 years (N=267) and 56 (23.5%) adults (N=239) had anxiety or depression as a complication, 1 child (0.4%) and 8 adults (3.3%) had another non-specified mental health condition, and 8 children (3.0%) and 6 adults (2.5%) had attention deficit hyperactivity disorder (ADHD) [38] . A retrospective case-controlled study of 34 African children with CF attending two CF centers in South Africa similarly found low rates of mental health complications: learning difficulties were reported in 2 (5.9%) children with CF compared to 1 control (2.9%), and ADHD was not reported in any children with CF compared to 3 controls (8.8%). [39] Finally, there was a qualitative, pre-modulator, case study exploring biopsychosocial risk and protective factors in 6 adolescents living with CF from SA, all classified as middle to upper class [39] . These adolescents experienced an array of emotions, including the need to be understood, and loss and bereavement linked to their illness, and when friends with CF died. Constructive internal dialogue and positive thinking were protective factors, and despite the severity of their symptoms and the demands of managing CF, they expressed hope for the future, finding some meaning in the illness. [39] Middle East In the Middle East, CF is common in the Arab population, with the incidence ranging from 1:1000 (Saudi Arabia) to 1:5800 live births [40] . In Jordan, for example, the incidence is 1:2560 live births [41] , which is similar to the incidence in the US. However, there are many barriers to early diagnosis. Ironically, the most prevalent mutation in the Arab population is F508del, which is also the most common mutation in the US and the mutation targeted by newer genetic modulators. There are no national CF registries in Arab countries, and no newborn screening programs have been implemented [41] . Additional barriers to early diagnosis include a lack of follow-up sweat testing and genetic screening to confirm the diagnosis. A few pilot programs have been funded in higher-income countries (United Arab Emirates), but they have not led to national newborn screening programs. Further, standard CF therapies, such as pancreatic enzymes and inhaled mucolytics, are very expensive and must be paid for by families or national charities. Stressors for families of children with CF in Arab countries include delays in diagnosis, lack of knowledge about CF among healthcare providers (e.g., pediatricians, nurses, pulmonologists), lack of specialized CF care, lack of access to standard therapies, and lack of reimbursement for standard medications, which results in very high costs for parents (Middle East CF Association [42] . These families face significant socioeconomic disadvantages, including poverty, limited health literacy, and poor access to treatments. They also face greater stress due to stigma, shame, and a lack of societal awareness of CF, exacerbating symptoms of depression and anxiety. [43] A recent qualitative study of the lived experiences of Jordanian parents of children with CF highlights the psychological challenges they face [44] . Using purposive sampling, 25 parents were recruited for face-to-face, semi-structured interviews. Children ranged in age from 1 to 18 years; mothers were interviewed with their husbands. Topics included: responses to the diagnosis of CF, early experiences of caring for their child, how this experience has impacted their lives, social support systems they can access, and expectations for the future (Table 4). Social support and an opportunity to share their experiences are the focus of a parent support group in Jordan sponsored by the Syrian American Medical Society (SAMS). SAMS serves approximately 200 families in Jordan, providing home visits for individual therapy, support groups for parents, and capacity building in the areas of psychological, material, and social needs. They conducted a pre-assessment and found that 80% of mothers reported significant levels of depression, anxiety, and sleep problems, and 90% of families face difficult living conditions. Psychological services are very hard to access due to cost, lack of transportation, and fear of new environments. Rowida Tailakh, an experienced psychologist and Senior Social Protection Project Officer at SAMS, is leading these 6-weekly, 90-minute sessions for parents. The goals are to empower parents, address their complex needs, foster positive parenting, teach mothers stress management techniques, and advice on how to prioritize self-care. Six topics were addressed: 1) Understanding and managing anger (e.g., bullying of the child), 2) Addressing anxiety and depression, 3) Managing sleep problems, 4) Parenting skills including accessing emotional support, communicating effectively, and building strong parent-child connections, 5) Self-care for parents including stress management and relaxation techniques, building a support network, and taking time for yourself, and 6) Continuation of strategies for self-care and emotional wellbeing and wrap-up. Mothers described feeling blamed for the child’s condition, lack of education about CF, caring for multiple children with CF, and experiences of losing a child to CF (Table 4). The only study of mental health using structured diagnostic interviews, [45] compared 32 children with CF in Turkey, ages 8 to 16 years, to 33 age- and sex-matched controls. Using the Kiddie Schedule for Affective Disorders and Schizophrenia [46] , 80% of children with CF ages 8-11 years and 50% of those 12-17 years had at least one psychiatric diagnosis. Anxiety disorder was diagnosed in 46.8%, attention deficit hyperactivity disorder in 21.8%, and depression in 21.9%. Significant differences were found between children with CF and controls on the Children’s Depression Inventory (CDI) and on a generic health-related quality of life measure. Although Turkey is considered an upper-middle income country, these results indicate that mental health symptoms are also very common in middle-income countries. In a study of depression, anxiety and hopelessness in children with CF in Egypt, 40 children with CF ages 7 to 12 were compared to 40 healthy children who were matched for age and sex. The two groups differed significantly on all measures: 60% of the children with CF were depressed on the CDI, 55% were elevated on an anxiety measure, and 100% of these children endorsed high rates of hopelessness. Importantly, duration of disease was positively correlated with all 3 mental health measures. The authors also measured several social determinants of health; 27.5%-30% of parents were categorized as illiterate, 75% were considered low income and a majority living in urban (62.5%) vs rural settings. A new initiative to integrate mental health into CF care has been launched in collaboration with Boston Children’s Hospital (Drs. Carolyn Snell and Ahmet Uler). It is called the Mideast CF Mental Health meeting and brings together providers from Turkey, Jordan and the US. The goals of the meetings are to share information, education and training among CF clinicians. Asia: South and Central Asia The challenges of CF care in South Asian countries such as India and Pakistan are very similar to those discussed for Africa and the Middle East. There is a lack of newborn screening, as well as the availability of follow-up sweat testing and genetic analysis. One additional challenge is the heterogeneity of CF mutations, with F508del appearing very rarely. As discussed previously, most LMIC countries cannot afford the new highly effective modulators such as ETI and Alyftrek Ⓡ . Still, in the case of South Asia, these medications may not be approved due to genotype. [47] Specialized CF Centers, trained healthcare providers, and public awareness of CF are also lacking [48] . In the first comprehensive study of genetic profiles in 48 children with CF in Mumbai, India, many of the genotypes identified conferred more severe pulmonary and gastrointestinal symptoms, and few of these mutations are found in Western countries. Thus, these studies highlight the importance of building the infrastructure that will facilitate region-specific mutation panels. [49] In Northern India, investigators performed a retrospective chart review of 178 children with CF between 2010 and 2020 [50] to identify the predictors of mortality and the mortality rate. Median age at diagnosis was 3.2 years, indicating that most children were not diagnosed in infancy. The most common predictors of mortality were neonatal complications, followed by low body mass index (BMI) and poor nutrition, lower lung function, and lack of access to specialized care. The mortality rate in this cohort study was 18%. Currently, India invests very little in the infrastructure needed to diagnose and treat rare diseases. [51] In one of the very few studies addressing psychosocial issues for PWCF in India, 30 adolescents ages 12-18 years attending a specialty clinic in New Delhi were enrolled using purposive sampling. [52] Sociodemographic data, clinical profiles, depressive symptoms (PHQ-9), and measurement of coping strategies on a CF-specific Ways of Coping questionnaire were completed. Adolescents were on average 14.9 years old, with about half of the sample from the upper to upper-middle class. Most followed the Hindu religion (86.7%) and lived in urban areas (93.6%). In terms of health outcomes, the majority had moderate to severe pulmonary disease (FEV1% values ranging from 40-69% [36.7%] and an additional 33.3% or wasting (40%). Scores on the PHQ-9 indicated that 70% reported mild to severe depressive symptoms, with girls reporting significantly higher depression scores than boys. The most frequent coping strategies used by these adolescents were: 1) hopefulness (76.6%), 2) optimistic acceptance (70.23%), and 3) avoidance (62.08%). The most used coping strategy was “I have confidence in the doctors and treatment.” Associations between demographic and clinical variables and depression scores revealed only one significant correlation–weight for age. Adolescents with moderate to severe depression were referred to an outside mental health expert since there are no mental health providers at the CF clinic. CF care in Central Asian countries is slightly better than in South Asia. A recent survey study was conducted in Kazakhstan, Kyrgyz Republic, Tajikistan, Turkmenistan, and Uzbekistan. The survey was sent to seven clinicians to obtain insights into their current practices. [53] Although no responses were received from Turkmenistan, responses were provided by four senior clinicians representing the remaining countries. A total of 568 PWCF were identified, primarily from Uzbekistan (n=309) and Kazakhstan (n=199). Pediatric patients accounted for 94% of the identified population. Importantly, CF registries in Kazakhstan and the Kyrgyz Republic collect data and send it to the ECFSPR (ECSF Patient Registry). In April 2025, Uzbekistan became the first country in Asia to implement newborn screening. Genetic analysis is available in each country; however, access is limited due to costs and regional differences. Several standard CF therapies are available, such as pancreatic enzymes and hypertonic saline; rhDnase and inhaled antibiotics are also available in Kazakhstan and Uzbekistan. There is also a new program in Kazakhstan to provide ETI for 40 PWCF. Unfortunately, no published studies on the psychological or psychosocial impacts of CF in Central Asia were found. Given that several of these countries are providing data to the ECFS CF Patient Registry, there may be opportunities to translate the mental health initiatives established by ECFS into countries in Central Asia. Latin America Brazil, the largest country in South America, is a model of CF care in Latin America. It is considered an upper-middle-income country and has developed the best infrastructure and care for CF, mainly due to the “father of CF” in Brazil, Dr. Jose Rodriguez Couri, who began establishing CF centers in the 1960s-1970s and led the development of a national CF Registry in 2009. Newborn screening is available in all states in Brazil, and they have access to ETI, although 30% of Brazilians with CF are not eligible for ETI based on genotype. Brazil hosts a national CF Conference every 2 years and invites prominent researchers and clinicians from the US and Europe to speak and provide educational and scientific updates. The first author of this review (ALQ) has spoken at this conference several times, training CF providers in mental health screening and intervention, as well as behavioral strategies for improving adherence. A recent study of 218 adolescents with CF at 14 CF referral centers in Brazil (13.7% of the adolescent CF population) was conducted between 2017 and 2019, measuring depression and anxiety using the screening measures recommended in the International Guidelines .[54] The prevalence of depression (using PHQ-9) was 19.1% and the prevalence of anxiety (GAD-7) was also 19.1%. Most adolescents (67%) reported low adherence to CF treatments on a self-report measure; both depression and anxiety scores were inversely related to adherence. Adolescents who were depressed or anxious above the clinical cut-score were less likely to do their prescribed treatments. Only two other Latin American countries are currently screening mental health symptoms in PWCF: Chile and Uruguay. In addition to Brazil, several other Latin American countries have newborn screening: Mexico, Argentina, Uruguay, Colombia, Peru, and Costa Rica. In most Latin American countries, there is limited or no access to ETI, and in several cases (i.e., Chile), families must be able to afford to sue the government to access the medication. One interesting exception to this is Argentina, which has developed its own generic formulation of ETI (Trixacar Ⓡ ); however, its availability is limited. Conclusions This review has highlighted the many challenges faced by LMICs in providing state-of-the-art care for CF. The health disparities for children with CF in high-income versus LMICs are vast, leading to greater morbidity and much earlier mortality for PWCF. Most of these countries lack newborn screening to diagnose CF in infancy, leading to significant malnutrition and failure to thrive. In most of these countries, children do not have access to standard CF therapies, let alone the newest life-saving genetic modulators. Delays in diagnosis and treatment, lack of information about the genetic cause of CF, high rates of consanguinity and social stigma lead to high rates of stress, depression, and anxiety in parents of children with CF. Despite these health disparities, it is critically important to address the mental health difficulties faced by PWCF and their families. Several successful, low-cost programs that been successful in addressing parental stress, depression, and anxiety while providing crucial education and social support. We have several recommendations that may increase the mental health parity between PWCF in LMICs and their wealthier counterparts (Table 5): 1. The Twinning project, sponsored by ECFS, is a successful model for providing education, training, and mentorship to CF providers in LMICs. The US CF Foundation could launch a twinning project with its neighbors to the south–Mexico, Colombia, Peru, Honduras, and Guatemala–helping them advance the medical and psychosocial care of PWCF. 2. We strongly recommend initiating annual screening of depression and anxiety in PWCF > 12 years of age and their parents. The recommended screening tools are brief, free, and available in most world languages. New translations could also be created. 3. Mental health screening of depression and anxiety has been successfully integrated into CF care in the US and much of Europe. The screening process itself is an intervention, raising awareness, normalizing these common symptoms, reducing stigma. and providing informal psychological support. [29] PWCF and their families have welcomed it as an acknowledgment of their emotional experience and a pathway to improving their coping skills and quality of life [55] 4. There are several evidence-based, low-cost psychological interventions that have been used successfully in low-resourced countries, leveraging digital technologies (cell phones, telehealth) for serious chronic conditions, such as HIV-AIDS, diabetes, and CF. [56,57] 5. The CFF Mental Health Advisory Committee has developed numerous educational materials that could be translated and shared with providers in LMICs. These materials cover a wide range of topics (e.g., coping with pain, medical traumatic stress, palliative care, mental health side-effects of modulator therapies). They are free and downloadable. 6. ECFS has launched a new project offering funding to 10 LMICs to add their data to the ECFS Registry over the next 5 years. References Acknowledgements Rowida Tailakh, Senior Social Protection Project Officer and Psychologist at the Syrian American Medical Society (SAMS) Foundation , contributed to the development of the mental health screening assessment. The tool was designed by the SAMS Psychosocial Support team and includes pre- and post-assessments tailored to the program’s focus areas. Katarína Štěpánková, MD; Slovak Cystic Fibrosis Association. Ambassador for the Twinning Expansion Project; contributed to information related to the Twinning Project. Claire Francis,Twinning Project Coordinator, contributed to information related to the Twinning Project. Irma Tash, MD; Chief Adult Center of Cystic Fibrosis, University Lung Department, Rajonal Hospital of Tirana Shefqet Ndroqi - contributed to the collection of data related to Albania. Supplementary Material File (figures_ped pulmon lmic.docx) Download 282.67 KB File (tables_lmic 9-30-25.docx) Download 37.03 KB Information & Authors Information Version history V1 Version 1 01 October 2025 Peer review timeline Published Pediatric Pulmonology Version of Record 10 Mar 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anxiety depression mental health screening psychological support Authors Affiliations Alexandra L. Quittner [email protected] Joe DiMaggio Children's Hospital View all articles by this author Sonia Graziano 0000-0002-7478-8414 Ospedale Pediatrico Bambino Gesu IRCCS View all articles by this author Minu P. Mohan University at Buffalo Jacobs School of Medicine and Biomedical Sciences View all articles by this author Beth Smith University at Buffalo Jacobs School of Medicine and Biomedical Sciences View all articles by this author Metrics & Citations Metrics Article Usage 254 views 136 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Alexandra L. Quittner, Sonia Graziano, Minu P. Mohan, et al. Advancing Mental Healthcare for Individuals with Cystic Fibrosis in Low- and Middle-Income Countries. Authorea . 01 October 2025. 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