Rethinking Long-Term Follow-Up of CPAP Therapy in Obstructive Sleep Apnea: Toward Personalized and Integrated Care

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I would like to thank the authors for giving me the opportunity to review their work. I think this is a good narrative review with a worthwhile message. It is clinically oriented and I want also to emphasize on the quality of the figures that could be very helpful for the reader. Also the review is up-to-date with mentioning of all the current clinical/research directions.

Having said that I also need to be more critical about the lack of a coherent network to address the central argument that was promised to the readers in the title : “Rethinking long-term follow-up”. The model of figure 2 should be also shown in the flow of the text, that now reads more as a collection of references about previous work. Also the strength of some of the claims of the model are not that well supported by the literature. For example : “low arousal threshold patients require closer follow-up”. I would suggest the general tone to be more mild and more suggestive, rather than guidelines-like. This agrees with the current discrepancy between scientific progress in studies and clinical practice; not eveyone has the capability/software to define all the endotypes for all the patients. We need to remain pragmatic.

Moreover, even for a narrative review, the methodology reads quite superficial. I would like to read more about their search strategy, inclusion criteria and quality control.

My advice to the authors is to reduce repetition in the text, such as re-introducing the value of PAP-adherence in every phase (also limit the self-reference?), strengthen the synthesis of the proposed framework and tone down recommendations that exceed available evidence.

Author Response

Comment 1) The model of figure 2 should be also shown in the flow of the text, that now reads more as a collection of references about previous work.

Response 1) We sincerely thank the Reviewer for this constructive and balanced assessment of our manuscript and for recognizing its clinical relevance, updated scope, and the potential value of the figures. We agree that the previous version did not sufficiently connect the reviewed evidence with the proposed long-term follow-up framework. We have therefore substantially reorganized the manuscript to make the conceptual pathway underlying Figure 2 explicit in the discussion.

Comment 2) Also the strength of some of the claims of the model are not that well supported by the literature. For example : “low arousal threshold patients require closer follow-up”. I would suggest the general tone to be more mild and more suggestive, rather than guidelines-like. This agrees with the current discrepancy between scientific progress in studies and clinical practice; not eveyone has the capability/software to define all the endotypes for all the patients. We need to remain pragmatic.

Response 2) We thank the Reviewer for this important observation and fully agree that the previous version occasionally presented emerging evidence with an excessively prescriptive tone. In particular, the association between low respiratory arousal threshold and poorer CPAP adherence does not currently demonstrate that patients should be routinely assigned to intensified follow-up on the basis of this endotype. We have therefore substantially revised the section on OSA endotypes and the corresponding table. Endotypic characteristics are now presented as potentially informative adjuncts rather than validated criteria for determining follow-up intensity. We explicitly acknowledge that the available evidence is predominantly observational, that endotype-guided follow-up has not yet been prospectively validated, and that physiological endotyping requires analytical tools that are not routinely available in all sleep centres.

Comment 3) Moreover, even for a narrative review, the methodology reads quite superficial. I would like to read more about their search strategy, inclusion criteria and quality control.

Response 3) We thank the Reviewer for this comment and agree that the methodology reported in the original manuscript was insufficiently detailed. We have therefore repeated and documented the literature search using a structured, multi-database approach and substantially expanded the Methods section. The revised manuscript now reports the databases searched, the search period and date, the principal search concepts, language and publication restrictions, eligibility and exclusion criteria, duplicate removal, screening procedures, citation tracking, data extraction, and quality-control measures. In addition, we introduced a claim-oriented assessment of the included evidence. We specifically distinguished studies evaluating actual follow-up interventions from those reporting observational associations, and considered the presence of appropriate comparators, relevant clinical outcomes, control of confounding, feasibility, and generalizability.

Comment 4) My advice to the authors is to reduce repetition in the text, such as re-introducing the value of PAP-adherence in every phase (also limit the self-reference?), strengthen the synthesis of the proposed framework and tone down recommendations that exceed available evidence.

Response 4) We thank the Reviewer for this final recommendation. The issues raised in this comment were addressed through a comprehensive revision of the manuscript. First, repetitive statements regarding the clinical importance of PAP adherence were reduced across the Results and Discussion. The introductory section now establishes the relevance of adherence once, while subsequent sections focus more specifically on its determinants, the timing of follow-up, emerging physiological predictors, and the effects of telemedicine, without repeatedly reintroducing the same rationale. Second, the Discussion was substantially reorganized around the interconnected domains of the proposed framework, including the goals of long-term care, the critical follow-up timeline, multidimensional assessment, risk stratification, organization of care, digital monitoring, and treatment escalation or transition. This revision was intended to provide a clearer synthesis rather than a sequential summary of individual studies. Third, recommendations that were not directly supported by interventional evidence were moderated throughout the manuscript. Emerging concepts, particularly physiological endotyping, are now presented as potentially informative adjuncts rather than validated criteria for determining follow-up intensity.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Editor,

I would like to thank the authors of the manuscript ID healthcare-4414439 entitled "Rethinking Long-Term Follow-up in Obstructive Sleep Apnea: Toward Personalized and Integrated Care" for presenting the results of their narrative review on long-term management strategies and follow-up approaches in patients with obstructive sleep apnea (OSA).

The manuscript presents the results of a narrative review of scientific research studies published on PubMed/MEDLINE from 2000 to 2025 using the keywords: “obstructive sleep apnea”, “continuous positive airway pressure”, “telemedicine”, “follow-up”, “long-term management,” “artificial intelligence”.

Main objectives were to define 1) the importance of follow-up in OSA treatment; 2) the factors influencing follow-up; 3) the impact of follow-up timing; 4) the significance of an instrumental follow-up; 5) differences between endotypes concerning adherence; 6) the impact of telemedicine in CPAP adherence.

After reading this article in detail, my main impression is that the article is very well written, in adherence to the Journal's standards, and addresses a very important issue of long-term management strategies in patients with obstructive sleep apnea. Sleep disorders are very prevalent in the adult population and if left unrecognized or untreated, can lead to serious consequences on patients' health and quality of sleep and life.

There are several issues for consideration:

1. Title: Not adequate. The whole review is focused on the CPAP treatment of OSA only, so it should be mentioned somewhere in the title. Personalized and integrated care sounds nice, but that type of care includes several other treatment options, from positional to surgical, MAD, hypoglossal nerve stimulation, dietary, etc., to sleep hygiene measures.
2. Abstract: Adequate
3. Introduction: Adequate.

Despite the clarity of the diagnostic and treatment approach to OSA, follow-up and long-term management remain poorly defined [7]; in fact, there are no standardized follow-up protocols or evidence-based recommendations [8]. There are several standardized follow-up protocols in different guidelines, from AASM, NICE, to national guidelines, etc. Please reformulate the statement

4. Methods: Not adequate. Not in line with the title “Rethinking Long-Term Follow-up in Obstructive Sleep Apnea: Toward Personalized and Integrated Care”. Focus is on CPAP, not all treatment modalities.
5. Results: Adequate but only for CPAP treatment
6. Discussion: Adequate but only for CPAP treatment.
7. References: Adequate, relevant, but only for CPAP treatment.
8. Tables and figures: Adequate, relevant, but only for CPAP treatment.

 

Author Response

Comment 1) Title: Not adequate. The whole review is focused on the CPAP treatment of OSA only, so it should be mentioned somewhere in the title. Personalized and integrated care sounds nice, but that type of care includes several other treatment options, from positional to surgical, MAD, hypoglossal nerve stimulation, dietary, etc., to sleep hygiene measures.

Response 1) We thank the Reviewer for this important observation and agree that the original title could be interpreted as referring to the comprehensive long-term management of OSA across all available treatment modalities, whereas the primary focus of the review is the follow-up of patients treated with CPAP. We have therefore revised the title to: “Rethinking Long-Term Follow-up of CPAP Therapy in Obstructive Sleep Apnea: From Device-Centred Monitoring to Personalized Care.”

Comment 2) Abstract: Adequate

Response 2) Thank you for the comment.

Comment 3) Introduction: Adequate. Despite the clarity of the diagnostic and treatment approach to OSA, follow-up and long-term management remain poorly defined [7]; in fact, there are no standardized follow-up protocols or evidence-based recommendations [8]. There are several standardized follow-up protocols in different guidelines, from AASM, NICE, to national guidelines, etc. Please reformulate the statement

Response 3) We thank the Reviewer for this correction and agree that the original statement was overly absolute. Several international and national guidelines, including those from the AASM and NICE, provide structured recommendations regarding early assessment, treatment monitoring, repeat sleep testing in selected circumstances, and periodic long-term follow-up. We have therefore removed the statement that no standardized protocols or evidence-based recommendations are available.

Comment 4) Methods: Not adequate. Not in line with the title “Rethinking Long-Term Follow-up in Obstructive Sleep Apnea: Toward Personalized and Integrated Care”. Focus is on CPAP, not all treatment modalities.

Response 4) We thank the Reviewer and agree that the scope described in the original Methods section was not sufficiently aligned with the actual focus of the review. As noted in our response to the comment regarding the title, the manuscript primarily examines the long-term follow-up of adults with OSA treated with CPAP rather than the comprehensive management of OSA across all available therapeutic modalities. In addition to revising the title, we have therefore substantially clarified the scope of the literature search and eligibility criteria. The revised Methods now explicitly state that the search focused on CPAP-treated OSA and included studies addressing treatment adherence and persistence, early troubleshooting, residual disease assessment, telemedicine, patient-reported outcomes, risk stratification, and the organization of CPAP follow-up.

Comment 5) Results: Adequate but only for CPAP treatment

Response 5) Thank you for the comment.

Comment 6) Discussion: Adequate but only for CPAP treatment.

Response 6) Thank you for the comment.

Comment 7) References: Adequate, relevant, but only for CPAP treatment.

Response 7) Thank you for the comment.

Comment 8) Tables and figures: Adequate, relevant, but only for CPAP treatment.

Response 8) Thank you for the comment.

Reviewer 3 Report

Comments and Suggestions for Authors

This narrative review brings a critical  discussion about the importance of CPAP adhesion, which are the main known risk factros for non-adhesion, how CPAP adhesion can be managed, and discussion of the different strategies. Each model is described in the text and listed in tables. 

As well, 2 figures show a proposal of flowcharts of follow-up´and treatment sequence. 

the text is very well written, and brings a good clinical insight about the necessity for a more personalized approach for CPAP treatment.

My only suggestion is to clarity the level of evidence which is known for each risk factor, intervention (I suggest to add a column for each table bringing this information of level of evidence). This evaluation also gives the baseline for what research/ studies ared needed for future (including 1 sentence paragraph in the discussion). 

Author Response

Comment 1) This narrative review brings a critical  discussion about the importance of CPAP adhesion, which are the main known risk factros for non-adhesion, how CPAP adhesion can be managed, and discussion of the different strategies. Each model is described in the text and listed in tables. As well, 2 figures show a proposal of flowcharts of follow-up´and treatment sequence. the text is very well written, and brings a good clinical insight about the necessity for a more personalized approach for CPAP treatment. My only suggestion is to clarity the level of evidence which is known for each risk factor, intervention (I suggest to add a column for each table bringing this information of level of evidence). This evaluation also gives the baseline for what research/ studies ared needed for future (including 1 sentence paragraph in the discussion). 

Response 1) We sincerely thank the Reviewer for the favorable assessment of our manuscript and for this valuable suggestion. We agree that the original tables did not allow readers to immediately distinguish between findings supported by interventional evidence and those based primarily on observational, preliminary, or narrative evidence. We have therefore added a new column entitled “Evidence type and maturity” to Tables 1–3. This column identifies the principal study design, peer-review status, consistency, and clinical maturity of the evidence supporting each risk factor, physiological trait, and telemedicine intervention. In particular, the revised tables now distinguish meta-analyses and randomized trials from registry-based or observational associations, device-validation studies, organizational evidence, and non-peer-reviewed preliminary findings. We also added a statement to the Discussion emphasizing the heterogeneous maturity of the available evidence and identifying the need for prospective validation of integrated risk-stratification and follow-up pathways, including evaluation of clinical effectiveness, healthcare utilization, and cost-effectiveness.

 

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript provides a timely and clinically relevant overview of long-term follow-up strategies in obstructive sleep apnea (OSA) and highlights several important developments, including telemedicine, phenotype-based management, and multidisciplinary care models. The review is generally well organized, the figures are informative, and the topic is of clear interest to clinicians involved in sleep medicine. However, several relatively minor issues should be a

First, the methodology section would benefit from greater transparency. Although the authors describe their work as a narrative review, the literature search strategy remains relatively brief and lacks sufficient detail regarding study selection, screening procedures, and inclusion criteria. Providing a more structured description of how references were identified and selected would improve reproducibility and reduce the possibility of selection bias. In addition, some statements throughout the manuscript rely on very recent publications, preprints, or narrative evidence; therefore, the strength of evidence supporting key recommendations should be more clearly differentiated. 

 

Second, several sections would benefit from a more balanced discussion of limitations. While the authors appropriately emphasize the potential benefits of telemedicine and phenotype-driven follow-up, the practical challenges associated with implementation—including healthcare infrastructure requirements, reimbursement issues, digital literacy, and regional differences in healthcare systems—deserve greater attention. Similarly, some proposed follow-up pathways and risk-stratification models are presented as future directions rather than approaches supported by robust prospective evidence.

Finally, minor editorial improvements are recommended. Several grammatical inconsistencies, formatting issues, and repetitions are present throughout the text. Abbreviations should be standardized, figure legends could be shortened for readability, and some tables may be condensed to avoid redundancy with the main text. Additionally, a concise section summarizing current knowledge gaps and future research priorities would further strengthen the clinical impact of the review. Overall, the manuscript is suitable for publication after minor revision. 

Comments on the Quality of English Language

Minor revision

Author Response

Comment 1) First, the methodology section would benefit from greater transparency. Although the authors describe their work as a narrative review, the literature search strategy remains relatively brief and lacks sufficient detail regarding study selection, screening procedures, and inclusion criteria. Providing a more structured description of how references were identified and selected would improve reproducibility and reduce the possibility of selection bias. In addition, some statements throughout the manuscript rely on very recent publications, preprints, or narrative evidence; therefore, the strength of evidence supporting key recommendations should be more clearly differentiated. 

Response 1) 

We thank the Reviewer for this important comment and agree that the original Methods section did not provide sufficient detail regarding the identification and selection of the literature. We have substantially expanded this section to report the databases searched, search period and final search date, database-specific search concepts, eligibility and exclusion criteria, duplicate removal, title and abstract screening, full-text assessment, citation tracking, data extraction and quality-control procedures. We also agree that the different levels of evidence supporting the components of the proposed framework should be more clearly distinguished. Higher-level and interventional evidence was given greater interpretative weight, while observational studies were used mainly to describe associations, and narrative reviews to provide conceptual or organizational context. Preprints and non-peer-reviewed sources were re-evaluated and were not used as the sole basis for clinical recommendations. The preprint concerning the Low ArTH Driven profile is now explicitly identified as preliminary evidence, and the related statements have been moderated. The non-peer-reviewed estimate of economic savings has been specifically declared as white paper non-peer reviewed. Organizational models derived partly from narrative evidence are now presented as adaptable and context-dependent proposals rather than established standards of care.

Comment 2) Second, several sections would benefit from a more balanced discussion of limitations. While the authors appropriately emphasize the potential benefits of telemedicine and phenotype-driven follow-up, the practical challenges associated with implementation—including healthcare infrastructure requirements, reimbursement issues, digital literacy, and regional differences in healthcare systems—deserve greater attention.

Response 2) We thank the Reviewer for this important observation and agree that the original manuscript placed greater emphasis on the potential benefits of telemedicine and endotype-driven follow-up than on their implementation challenges. The revised manuscript now addresses the need for reliable digital infrastructure, platform interoperability, integration with electronic health records, trained personnel and clear allocation of professional responsibilities. We also discuss the possibility that telemonitoring may increase workload when alerts and escalation pathways are not adequately structured. In addition, we now acknowledge that reimbursement for remote monitoring, digital consultations, and home-care provider activities varies considerably across healthcare systems and may limit scalability. Regional differences in specialist availability, regulatory frameworks, digital infrastructure, and organization of care may also reduce the generalizability of models developed in integrated or well-resourced settings. Patient-related barriers, including limited digital literacy, unequal internet or device access, cognitive or sensory impairment, language barriers, and privacy concerns, have also been incorporated. We now suggest that hybrid pathways combining remote and in-person care may be more appropriate for selected populations. Finally, we clarified that advanced physiological endotyping is not universally feasible, because it requires specialized signals, software, expertise, and additional resources. The proposed framework is therefore now explicitly described as adaptable to local healthcare capacity rather than as a universally standardized pathway.

Comment 3) Similarly, some proposed follow-up pathways and risk-stratification models are presented as future directions rather than approaches supported by robust prospective evidence.

Response 3) We thank the Reviewer and agree that the original manuscript did not sufficiently distinguish between individual components supported by interventional evidence and the proposed integrated framework, which has not yet been prospectively validated as a complete care pathway. We now explicitly state that no validated risk score or universally accepted thresholds are currently available to allocate patients to standard versus intensified follow-up. Risk stratification is therefore presented as a pragmatic multidimensional assessment based primarily on routinely available variables, including early PAP use, treatment tolerance, residual symptoms, comorbidities, and patient-reported outcomes. The revised Discussion also differentiates components supported by interventional evidence, such as early troubleshooting and active telemonitoring, from organizational and phenotype-informed pathways supported mainly by observational studies, feasibility studies, or expert synthesis. Finally, we emphasize that prospective comparative studies are required to validate the integrated framework and assess its effects on adherence, clinical outcomes, healthcare utilization, and cost-effectiveness.

Comment 4) Finally, minor editorial improvements are recommended. Several grammatical inconsistencies, formatting issues, and repetitions are present throughout the text. Abbreviations should be standardized, figure legends could be shortened for readability, and some tables may be condensed to avoid redundancy with the main text. Additionally, a concise section summarizing current knowledge gaps and future research priorities would further strengthen the clinical impact of the review.

Response 4) We sincerely thank the Reviewer for this favorable assessment and for the helpful editorial recommendations. The manuscript has undergone comprehensive linguistic and formatting revision to correct grammatical inconsistencies, typographical errors, and repetitive statements. Terminology, capitalization, hyphenation, and abbreviations have been standardized throughout the abstract, main text, tables, and figures. The figure legends have been shortened to improve readability and to avoid repeating information already presented in the main text. The tables have also been condensed, with detailed numerical findings retained primarily in the tables and the corresponding narrative sections revised to focus on interpretation and synthesis. Finally, we added a new subsection entitled “Knowledge Gaps and Future Research Priorities” at the end of the Discussion. This section outlines the need for prospective validation of follow-up timing and risk-stratification criteria, standardized multidimensional outcome sets, evaluation of the incremental value of physiological endotyping and digital tools, and implementation studies addressing cost-effectiveness, reimbursement, infrastructure, digital literacy, and health equity.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Editor,

 

I would like to thank the authors of the revised manuscript ID healthcare-4414439 entitled "Rethinking Long-Term Follow-up in Obstructive Sleep Apnea: Toward Personalized and Integrated Care" for presenting the results of their narrative review on long-term management strategies and follow-up approaches in patients with obstructive sleep apnea (OSA).

 

The manuscript presents the results of a narrative review of scientific research studies published on PubMed/MEDLINE from 2000-2025 using the keywords: “obstructive sleep apnea”, “continuous positive airway pressure”, “telemedicine”, “follow-up”, “long-term management,” “artificial intelligence”.

Main objectives were to define 1) the importance of follow-up in OSA treatment; 2) the factors influencing follow-up; 3) the impact of follow-up timing; 4) the significance of an instrumental follow-up; 5) differences between endotypes concerning adherence; 6) the impact of telemedicine on CPAP adherence.

After reading this article in detail, my main impression is that the article is very well written, in adherence to Journal's standards, and addresses a very important issue of long-term management strategies in patients with obstructive sleep apnea. Sleep disorders are very prevalent in the adult population, and if left unrecognized or untreated, can lead to serious consequences on patients' health and quality of sleep and life.

There are several issues for consideration:

1. Title: Adequate. Remarks addressed.
2. Abstract: Adequate
3. Introduction: Adequate. Remarks addressed
4. Methods: Adequate. Remarks addressed
5. Results: Adequate. Remarks addressed

• A study by Palm A et al showed that the risk of CPAP withdrawal decreases by 13% for every 10-year increase in age (aRRR 0.87). What is aRRR?

6. Discussion: Adequate. Remarks addressed.
7. References: Adequate. Remarks addressed.
8. Tables and figures: Adequate. Remarks addressed.

Author Response

Comment 1: Title: Adequate. Remarks addressed.

Response 1: thank you.

Comment 2: Abstract: Adequate
Response 2: thank you.

Comment 3: Introduction: Adequate. Remarks addressed.

Response 3: thank you.

Comment 4: Methods: Adequate. Remarks addressed

Response 4: thank you.

Comment 5: Results: Adequate. Remarks addressed “A study by Palm A et al showed that the risk of CPAP withdrawal decreases by 13% for every 10-year increase in age (aRRR 0.87).” What is aRRR?

Response 5: We thank the Reviewer for highlighting this point. The abbreviation aRRR refers to the adjusted relative risk ratio. We have now revised the sentence as follows: “In a study by Palm A et al, each 10-year increase in age was associated with a 13% lower relative risk of CPAP non-adherence versus full adherence (adjusted relative risk ratio [aRRR] 0.87), after adjustment for sex, BMI, AHI, ESS, hypertension, and humidifier use [32].”

Comment 6: Discussion: Adequate. Remarks addressed.

Response 6: thank you.

Comment 7: References: Adequate. Remarks addressed.

Response 7: thank you.

Comment 8: Tables and figures: Adequate. Remarks addressed.

Response 8: thank you.