An umbrella review of reviews was conducted in accordance with PRISMA 2020 guidelines (9) and registered with PROSPERO (CRD42025214760). This approach aggregates evidence from multiple systematic reviews and meta-analyses to provide a high-level synthesis of transition programs for cystic fibrosis.

As this review of reviews synthesized only publicly available, aggregated data from previously published reviews, systematic reviews and meta-analyses, and involved no direct human interaction, collection of new identifiable information, or interventions on subjects, formal ethical approval was waived by the Institutional Review Board in accordance with national guidelines, with all included primary studies having already secured their own ethical clearances.

This review of reviews included only reviews, systematic reviews, with or without meta-analyses, that investigated transition care in individuals with confirmed cystic fibrosis (CF), following the PICO (Population, Intervention, Comparison, Outcome) framework. Eligible reviews addressed populations transitioning from pediatric to adult care, assessed structured or unstructured transition interventions, and reported at least one relevant outcome—clinical, psychosocial, or healthcare utilization. Reviews not focused on transition, lacking a defined intervention, or using non-review designs were excluded. Full inclusion and exclusion criteria, guided by the PICO approach, are detailed in Table 1.

A comprehensive and systematic literature search was conducted to identify reviews, systematic reviews and meta-analyses examining transition care in individuals with cystic fibrosis (CF). The search was performed across six major biomedical databases—PubMed/MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, and CINAHL (Cumulative Index to Nursing and Allied Health Literature)—covering the period from January 2005 through April 2025. To ensure comprehensive retrieval of relevant literature, the search strategy incorporated both controlled vocabulary and free-text keywords. Controlled terms included Medical Subject Headings (MeSH) in PubMed (e.g., “Cystic Fibrosis,” “Health Transition,” “Continuity of Patient Care,” “Adolescent Health Services”) and Emtree terms in Embase (e.g., “cystic fibrosis,” “transition to adult care,” “health care transfer”). Free-text terms included synonyms and variations such as “CF,” “transition of care,” “transfer to adult services,” “transition program,” “healthcare transition,” “care coordination,” “adolescent to adult care,” as well as methodological filters such as “review”, “systematic review” and “meta-analysis.” Boolean operators (AND, OR) were used to combine concepts and refine the search, and truncation symbols were applied to capture all relevant term variations.

No language restrictions were applied to the search to maximize inclusivity and reduce any bias. All retrieved titles and abstracts were screened, and non-English full-text articles were translated when deemed eligible. Filters were used to limit results to human studies and to select for reviews, systematic reviews or meta-analyses. Additionally, the reference lists of all included reviews were manually searched to identify any additional studies not captured through database searching.

The screening and selection of studies were conducted through a structured and transparent process, adhering to the PRISMA 2020 guidelines. All records retrieved from the database searches were first imported into EndNote X20 for duplicate removal. The deduplicated references were then uploaded into Rayyan, a web-based platform for systematic review screening (10). Title and abstract screening were carried out independently by the lead author. Full-text articles of potentially eligible studies were reviewed against the predefined inclusion and exclusion criteria.

Study screening was performed by the author (A.A.), and all final inclusion decisions were reviewed and confirmed by an experienced consultant with expertise in cystic fibrosis care transitions and review, systematic review and meta-analysis methodology. Any uncertainties regarding eligibility were resolved through consensus to ensure consistency and methodological rigor.

The PRISMA 2020 flow diagram (Figure 1) (11) summarized the number of records identified, screened, assessed for eligibility, and included in the final synthesis, along with reasons for exclusions at each stage. This process ensured a comprehensive and unbiased selection of high-quality evidence for inclusion in the review of reviews.

Data extraction was performed systematically using a standardized spreadsheet template aligned with the variables presented in Table 2. For each included review, the following information was extracted: first author, year of publication, country or region of focus, number of primary studies included, total sample size (if reported), type of transition model evaluated, clinical and psychosocial outcomes assessed, and the review's key conclusions. Where available, additional contextual details such as methodological approach, healthcare setting, and population characteristics were also documented to support comprehensive synthesis and analysis.

Across the included reviews and systematic reviews, clinical and psychosocial outcomes were assessed using a range of validated and non-validated instruments. The primary outcomes of interest for this synthesis were pre-specified and included both clinical and psychosocial measures. Clinical outcomes of interest were forced expiratory volume in 1 s (FEV₁), body mass index (BMI), hospitalization rates, and mortality. Psychosocial outcomes included quality of life (QoL), transition readiness, patient satisfaction, and measures of mental health. Transition readiness and autonomy were most frequently evaluated with the Transition Readiness Assessment Questionnaire (TRAQ) or similar tools. Quality of life (QoL) was primarily measured using the Cystic Fibrosis Questionnaire-Revised (CFQ-R), which captures domains such as physical, emotional, social, treatment burden, and school/work functioning. Mental health outcomes were occasionally reported, most often through validated instruments such as the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms and the Generalized Anxiety Disorder-7 (GAD-7) scale for anxiety, although use was inconsistent. Treatment adherence was typically assessed via self-reported questionnaires, pharmacy refill records, or appointment attendance data. Patient and parent satisfaction were reported using ad hoc surveys or study-specific questionnaires.

The methodological quality of the included reviews was assessed using AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews 2), a validated tool specifically designed to evaluate the quality of systematic reviews of healthcare interventions (12). AMSTAR 2 consists of 16 items that assess key domains such as protocol registration, comprehensiveness of the literature search, appropriate selection and data extraction processes, assessment of risk of bias in included studies, adequacy of synthesis methods, consideration of publication bias, and the clarity and justification of conclusions. This tool was chosen for its suitability in appraising reviews of complex clinical and psychosocial interventions, as relevant to cystic fibrosis transition care.

Each review was independently assessed by the author (A.A.) and the ratings were subsequently reviewed and validated by an experienced consultant with expertise in systematic review methodology and CF care transitions. Discrepancies were resolved through discussion and consensus.

The potential overlap of primary studies across included systematic reviews was evaluated using the Corrected Covered Area (CCA) method (13). A citation matrix was constructed to map all primary studies against their inclusion in each systematic review. The total number of study inclusions (N) and unique primary studies (r) were recorded, along with the number of systematic reviews (c). The CCA index was calculated to quantify the degree of overlap, with established thresholds applied to interpret the results (5%–15% indicating moderate overlap;>15% indicating high overlap).

Data synthesis combined narrative and quantitative approaches, depending on the consistency and availability of outcome data across the included reviews and systematic reviews. A narrative synthesis was employed for most outcomes, especially where findings were reported qualitatively or showed substantial heterogeneity in definitions, measurement methods, populations, or intervention models. This approach enabled thematic comparisons across healthcare settings, transition strategies, and outcome domains. Outcomes such as hospitalization rates, treatment adherence, and psychosocial measures—including autonomy, quality of life, and transition readiness—were synthesized narratively due to inconsistent reporting and the absence of standardized metrics. Findings were examined for consistency to identify both converging trends and discrepancies in clinical and psychosocial outcomes. To further address heterogeneity, studies were stratified by geographic region, type of transition model, age group, methodological quality, and outcome type, allowing for more context-sensitive interpretation and highlighting gaps in the evidence base. Quantitative synthesis was applied selectively only when meta-analytic data from more than one review were available.

A formal tool specifically designed to assess the certainty of evidence in primary studies was not applied in this review of reviews, as such tools are not directly applicable when synthesizing data from reviews and systematic reviews rather than original research. Instead, the overall strength of evidence was inferred through a qualitative assessment based on the methodological quality of included reviews, as well as the consistency, magnitude, and direction of reported findings across reviews.

A total of 1,347 records were identified through comprehensive searches across six major databases—PubMed/MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, and CINAHL. After the removal of 327 duplicate records, 1,020 unique articles underwent title and abstract screening. During this phase, 973 records were excluded as they were not relevant to the review's scope.

The full text of 47 articles was sought for retrieval and assessed for eligibility. Of these, 37 reports were excluded for the following reasons: not being a review, systematic review, or meta-analysis (n = 15); not focusing on the pediatric-to-adult transition in cystic fibrosis (CF) (n = 9); not reporting relevant outcomes (n = 8); or not addressing transition-related factors (n = 5).Ultimately, 10 studies met the criteria for inclusion in the review (14–23). Among these, 4 studies were specifically focused on CF and formed the core of the analysis (17, 20, 22, 23). The study selection process is detailed in the PRISMA 2020 flow diagram (Figure 1).

A total of 10 reviews published between 2008 and 2025 were included, spanning multiple countries and transition model types. Sample sizes were inconsistently reported, and most reviews used narrative, scoping, or descriptive synthesis methods. Reported outcomes included psychosocial readiness, self-management, patient and parent satisfaction, healthcare utilization, autonomy, and clinical indicators such as FEV₁. Four studies (17, 20, 22, 23) were CF-specific, while six studies (14, 15, 16, 18, 19, 21) addressed transition in chronic illnesses with CF included as a key subgroup. Table 2 summarizes the characteristics of the included reviews on pediatric-to-adult transition programs in cystic fibrosis.

The methodological quality of the included reviews was appraised using AMSTAR 2. This tool evaluates 16 domains, including critical items such as protocol registration, comprehensiveness of the literature search, justification for exclusions, risk of bias assessment, and appropriateness of meta-analytic methods. As summarized in Table 3, none of the reviews registered a protocol a priori, and none conducted a meta-analysis. Only one review (21) achieved a moderate confidence rating, as it fulfilled most critical and non-critical domains, including a comprehensive search, risk of bias assessment, and justification for exclusions.

The remaining nine reviews were rated as critically low in confidence. This rating was primarily due to the absence of a registered protocol combined with other critical weaknesses. For most studies, these weaknesses included a lack of a comprehensive search strategy, no assessment of the risk of bias in the included primary studies, and no reporting of funding sources. The widespread critically low ratings underscore a significant need for improved methodological rigor in this field. Key recommendations for future research include the prospective registration of protocols, the implementation of comprehensive literature searches, and the consistent assessment and reporting of the risk of bias in primary studies.

Primary study overlap across the 10 included systematic reviews (14–23) was evaluated by constructing a citation matrix and calculating the Corrected Covered Area (CCA) to quantify redundancy. Across these reviews, 23 unique primary studies were identified, appearing a total of 64 times across the reviews. The CCA of 0.178 (17.8%) indicates a moderate degree of overlap, suggesting that while several primary studies were cited in multiple reviews—particularly those focusing on structured transition models and appointment adherence—a substantial portion of evidence remained unique, contributing additional insights to the overall synthesis. Table 4 illustrates the inclusion frequency of key primary studies across the systematic reviews, highlighting both commonly cited foundational studies and more recent or less integrated research.

Analysis of the citation matrix revealed that certain primary studies were consistently referenced across multiple reviews. For example, studies such as (18, 19) appeared in seven reviews each, often informing outcomes related to appointment adherence, autonomy, and transition readiness, while studies (21, 22) were frequently cited for psychosocial outcomes and patient engagement. Earlier foundational studies, including (16, 17), were commonly included in reviews addressing structured transition interventions. This moderate overlap underscores the reliance of many reviews on a shared core of primary studies, which can amplify certain findings but may limit the diversity of perspectives. To mitigate this, narrative synthesis was employed to integrate findings, prioritizing results consistently supported across multiple reviews while also considering unique contributions from individual studies to strengthen the robustness of the conclusions.

The ten included reviews (14–23) consistently identified essential components of effective cystic fibrosis (CF) transition programs, including interdisciplinary collaboration (14, 17, 20), standardized readiness assessments (19, 21), staged transition timelines (15, 21), and patient education tools (16, 18, 23). Structured transition models, ranging from clinic-based protocols (14) to multicomponent programs (16), were associated with improvements in clinic attendance (14), autonomy (15), self-management skills (16), and successful transfer to adult care (20), with geographic adaptations observed in German (15), Brazilian (17), and Spanish (23) settings. Key innovations included the RISE model's skill-building approach (19), stepwise frameworks for progressive responsibility (21), and multidisciplinary joint clinic designs (22), emphasizing both consensus on core transition elements and the importance of context-specific adaptation. Table 5 summarizes the structured transition models identified, including staged transition protocols, transition readiness assessment frameworks, joint clinic models, young adult clinics, eHealth-supported interventions, and the comprehensive parenthood transition model, with core components such as formal policies, dedicated coordinators, skill-based education, family involvement, digital health integration, and reproductive health support. Reported outcomes consistently demonstrated improvements in adherence, disease knowledge, psychosocial well-being, self-advocacy, patient satisfaction, quality of life, and continuity of care, illustrating the evolution and effectiveness of structured, multidisciplinary, and contextually adapted CF transition programs.

Psychosocial factors are central to the success of transition in cystic fibrosis (CF) care, yet across the 10 included reviews (14–23), evidence remains limited, variable in quality, and primarily descriptive. Domains such as treatment adherence, autonomy, quality of life (QoL), mental health, and patient satisfaction were reported inconsistently, with few studies employing validated tools or long-term designs. Structured, multidisciplinary transition models—particularly those incorporating education, readiness assessments, and care coordination—were generally associated with more favorable psychosocial outcomes.

Beyond the reviews and systematic reviews synthesized in this review of reviews analysis, explorations of the wider cystic fibrosis literature using diverse methodological approaches show that research activity remains concentrated in high-income regions. Most of these primary investigations have been conducted in the United States (48 studies), with further contributions from Canada (20), the United Kingdom (18), and other Western European countries (12). Smaller numbers have originated from Australia and New Zealand (7). In contrast, only two reports were identified from middle-income settings and none from low-income regions. Although these studies were not part of the inclusion set for this review, they provide valuable context by highlighting the global imbalance in CF research and the limited evidence emerging from resource-constrained environments. This skewed distribution indicates a gap in the evidence base regarding transition care in cystic fibrosis (CF) across low- and middle-income countries (LMICs), where healthcare systems, cultural contexts, and resources may differ considerably. Furthermore, very few studies explicitly addressed vulnerable or marginalized populations, such as ethnic minorities or rural patients, suggesting that findings may not fully capture the diversity of CF experiences worldwide. Figure 2 illustrates the uneven geographic representation of included primary studies.

A global comparison of cystic fibrosis (CF) transition care models highlights notable developments and regional disparities. In the Gulf Cooperation Council (GCC) countries, structured transition is emerging through pilot joint clinics, multidisciplinary teams, and patient/family education, showing early benefits such as increased patient satisfaction despite the absence of national policies or long-term outcomes (24–29). Kuwait remains largely informal, relying on pediatric follow-up and adult care referrals without standardized infrastructure (27). In South Asia, India has implemented a structured adolescent transition framework incorporating TRAQ and education, though limited adult CF centers constrain implementation (30), while Pakistan relies on NGO-led community initiatives without formal evaluation (31). East Asia exhibits pilot programs in China with limited adult services due to underdiagnosis (32), and Japan lacks formal transition pathways due to low prevalence (33). Malaysia has introduced pilot readiness clinics with early positive engagement outcomes (34).

In Africa, South Africa's registry-linked clinics demonstrate improved continuity of care despite challenges in drug access (35), and Egypt's task force model is in preliminary stages without systematic outcome reporting (36). Latin America shows moderate progress with Brazil's digital and public health–integrated São Paulo CF Program and Chile's national CF coordination efforts, though standardized outcome metrics remain limited (37, 38). These regional comparisons, while extending beyond the included systematic reviews, underscore health equity considerations, highlight evidence gaps in low- and middle-income settings, and offer practical insights for contextual adaptation of structured transition care. Table 8 provides a concise overview of these global CF transition models, detailing key components, strengths, limitations, and reported outcomes.

This umbrella review of reviews comprehensively synthesizes existing systematic reviews on cystic fibrosis transition, thereby filling an important gap in the literature. Key strengths include the use of an extensive, unrestricted search strategy that enhances global applicability, and adherence to PRISMA 2020 guidelines and PROSPERO registration, which ensures transparency. The use of AMSTAR 2 facilitated a structured quality assessment, while the Corrected Covered Area method provided valuable insight into primary study overlap. Together, these approaches supported a robust and nuanced narrative synthesis across diverse healthcare contexts.

Despite these strengths, several limitations must be acknowledged. A key limitation of this umbrella review is the small number of included systematic reviews. This restricts the breadth of the synthesis and precludes the drawing of strong, generalizable conclusions, as the evidence base may not be fully representative of the global landscape of CF transition careNone of the included systematic reviews achieved a high confidence rating on AMSTAR 2, reflecting frequent weaknesses such as unregistered protocols, incomplete assessment of risk of bias, and inadequate disclosure of funding sources. These issues reduce the certainty of the evidence synthesized here. In addition, outcome heterogeneity—both in terms of definitions and measurement approaches—limited the potential for quantitative meta-analysis and necessitated reliance on narrative synthesis, which may introduce subjectivity. The moderate overlap of primary studies across reviews (CCA: 17.8%) suggests some degree of saturation and potentially reduced diversity of findings. Furthermore, the body of evidence synthesized in this review was largely generated before the widespread clinical implementation of Highly Effective CFTR Modulator Therapies (HEMT). The profound impact of these therapies on disease stability and life expectancy means that the transition experience, associated challenges, and long-term outcomes for contemporary patients may differ from those reported in the current evidence base. Finally, the majority of primary studies included in the systematic reviews predated the widespread use of highly effective CFTR modulator therapies (HEMT). Given the transformative effect of HEMT on disease progression, their implications for transition processes and outcomes remain an essential area for future research. The conclusions of this review may therefore not fully reflect the experience of patients in the current treatment era.

The findings of this umbrella review of reviews have important implications for both clinical practice and healthcare policy concerning the transition of care for adolescents and young adults with cystic fibrosis. For practice, the evidence indicates that structured transition programs—characterized by interdisciplinary collaboration, standardized readiness assessments, staged timelines, and comprehensive patient education—are associated with improved outcomes (38). Healthcare providers are encouraged to adopt formal transition protocols in preference to ad hoc arrangements. Particular emphasis should be placed on readiness tools such as the CF RISE model, which facilitate the tailoring of transition plans to individual patients' self-management skills and psychosocial preparedness. Joint pediatric–adult clinics and dedicated transition coordinators further strengthen continuity of care, reduce risks of disengagement, and improve adherence.

At the policy level, there is a clear need for sustained investment in structured transition programs (39). Policymakers should prioritize the establishment of national or regional guidelines for transition care in CF and related chronic conditions, drawing on successful international models. Resources should support the development of multidisciplinary teams that include physicians, nurses, social workers, psychologists, and dietitians, as this collaborative approach is vital for holistic patient care (40). Additionally, the development of standardized and validated outcome measures for transition success should be promoted to allow for consistent evaluation and cross-comparison of program effectiveness across different settings.

Future research should build on current evidence by conducting high-quality systematic reviews with preregistered protocols and comprehensive bias assessments. At the primary study level, randomized controlled trials, where feasible, are needed to evaluate specific transition model components. Further work is also required to explore psychosocial outcomes using standardized and validated instruments, enabling clearer links to clinical success. Given the variability of CF care worldwide, additional studies from low-resource and culturally diverse settings are needed to assess the adaptability and generalizability of transition models. Long-term studies that evaluate adult health outcomes, quality of life, and healthcare utilization following structured transitions would provide further justification for sustained investment in these programs.