The Impact of Breathing Pattern (Nasal vs. Oral) on the Severity of Obstructive Sleep Apnea

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

1.The Discussion section should more thoroughly address the study's limitations. Key points include: (a) Sample Size: The sample of 60 patients (14 moderate, 46 severe), particularly the small subgroup with moderate OSA, may be underpowered to detect subtle associations between breathing pattern and AHI (Type II error). This could partly explain why a higher median AHI in oral breathers (40.5 vs. 36.4) did not reach statistical significance (p=0.8). (b) Subjective Assessment: The core variable "breathing pattern" relies entirely on patients' subjective​ daytime perception, which is a major limitation. Objective assessment tools mentioned in the text (e.g., rhinomanometry) were not used. The potential for recall bias and inaccurate perception in this self-report should be discussed, acknowledging it as a weakness and suggesting future studies incorporate objective measures (e.g., nocturnal breathing monitoring, rhinomanometry). (c) Patient Population: The exclusion of patients with prior nasal surgery or using nasal medications/steroids increases internal validity but limits the generalizability of the findings to a broader, more typical OSA population with comorbidities.

2.The Discussion should delve deeper into integrating and explaining the seemingly contradictory results: (1) Oral breathing is strongly associated with septal deviation/turbinate hypertrophy (p<0.001), yet (2) these structural abnormalities and their location show no relationship with AHI severity (p=0.93). The authors state that "the nose plays a limited role in determining disease severity." This could be expanded: Does this imply that in patients with established moderate-to-severe OSA, oral breathing is more a consequence (symptom) of structural nasal obstruction, rather than a primary pathophysiological driver of AHI severity? And that the primary determinants of AHI lie in collapsibility or neuromuscular control at other sites (e.g., oropharynx/hypopharynx)? This interpretation would add nuance to the conclusion.

3.The description of the nasal area classification (based on a modified Cottle system) in the Methods section could be clearer. The document mentions it was "partially adapted to reflect surgical anatomy" but does not detail how it was modified or how Areas III and IV specifically differ from the original Cottle classification. Suggest adding a brief table or more precise textual description defining the anatomical landmarks corresponding to each of the four areas used in this study to enhance reproducibility.

5.The Conclusion mentions identifying oral breathing as an indicator of a "potentially modifiable factor." It could be more specific: Based on these findings, clinicians should consider a more thorough nasal examination (e.g., endoscopy) for OSA patients reporting oral breathing. While isolated nasal correction may not dramatically reduce AHI, elaborate on how it might indirectly influence overall treatment success by potentially improving comfort and tolerance to CPAP therapy (e.g., reducing mouth leak, lowering required pressure), thereby linking back to points made in the Introduction and Discussion.

Author Response

1. The Discussion section should more thoroughly address the study's limitations. Key points include: (a) Sample Size: The sample of 60 patients (14 moderate, 46 severe), particularly the small subgroup with moderate OSA, may be underpowered to detect subtle associations between breathing pattern and AHI (Type II error). This could partly explain why a higher median AHI in oral breathers (40.5 vs. 36.4) did not reach statistical significance (p=0.8). (b) Subjective Assessment: The core variable "breathing pattern" relies entirely on patients' subjective daytime perception, which is a major limitation. Objective assessment tools mentioned in the text (e.g., rhinomanometry) were not used. The potential for recall bias and inaccurate perception in this self-report should be discussed, acknowledging it as a weakness and suggesting future studies incorporate objective measures (e.g., nocturnal breathing monitoring, rhinomanometry). (c) Patient Population: The exclusion of patients with prior nasal surgery or using nasal medications/steroids increases internal validity but limits the generalizability of the findings to a broader, more typical OSA population with comorbidities.

1. Response: Thank you for your comments. I fully agree that the small number of participants in the moderate OSA group may be the reason for this finding, namely the absence of a statistically significant difference. However, during the period defined for this study, this was the profile of patients who presented to our clinic. Subjective assessment of nasal breathing was chosen because it provides insight into the individual perception of nasal patency and the presence of respiratory difficulties, which we consider an important aspect of the participants’ functional status. The subjective sensation of impaired nasal breathing does not always correspond completely with objective findings; therefore, subjective assessments have considerable clinical and research value, particularly in evaluating symptoms and their association with quality of life and daily functioning. For this reason, we decided to rely solely on subjective assessment. I would not agree with your comment that it is typical for patients with OSA to have undergone previous nasal surgery or to use intranasal corticosteroid sprays. These exclusion criteria were specifically chosen to ensure the internal validity of the study. Based on your suggestions, I have incorporated the necessary revisions and explanations into the manuscript.
   
   2. The Discussion should delve deeper into integrating and explaining the seemingly contradictory results: (1) Oral breathing is strongly associated with septal deviation/turbinate hypertrophy (p<0.001), yet (2) these structural abnormalities and their location show no relationship with AHI severity (p=0.93). The authors state that "the nose plays a limited role in determining disease severity." This could be expanded: Does this imply that in patients with established moderate-to-severe OSA, oral breathing is more a consequence (symptom) of structural nasal obstruction, rather than a primary pathophysiological driver of AHI severity? And that the primary determinants of AHI lie in collapsibility or neuromuscular control at other sites (e.g., oropharynx/hypopharynx)? This interpretation would add nuance to the conclusion.
   2. Response: Thank you for your comment, and I fully agree with it. Therefore, we have further elaborated on the pathophysiological mechanisms underlying the development of the disease in the Discussion section in order to emphasize the multifactorial nature of OSA pathogenesis.
   
   3. The description of the nasal area classification (based on a modified Cottle system) in the Methods section could be clearer. The document mentions it was "partially adapted to reflect surgical anatomy," but does not detail how it was modified or how Areas III and IV specifically differ from the original Cottle classification. Suggest adding a brief table or more precise textual description defining the anatomical landmarks corresponding to each of the four areas used in this study to enhance reproducibility.
   3. Response: Thank you for your comment. We accept your suggestion and have added a table of classifications to the manuscript.
   
   5 .The Conclusion mentions identifying oral breathing as an indicator of a "potentially modifiable factor." It could be more specific: Based on these findings, clinicians should consider a more thorough nasal examination (e.g., endoscopy) for OSA patients reporting oral breathing. While isolated nasal correction may not dramatically reduce AHI, elaborate on how it might indirectly influence overall treatment success by potentially improving comfort and tolerance to CPAP therapy (e.g., reducing mouth leak, lowering required pressure), thereby linking back to points made in the Introduction and Discussion.
   5. Response: Thank you for your comment. We appreciate your suggestion and have revised the conclusion accordingly, in line with your recommendation

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is an interesting and clinically relevant study addressing the relationship between breathing patterns, nasal anatomy, and obstructive sleep apnea severity. However, several important methodological and interpretative issues require clarification before the manuscript can be considered for publication. In particular, the clinical meaning of subjectively assessed breathing patterns, the potential impact of unperceived nasal obstruction on the study conclusions, and the implications for treatment adherence warrant further discussion. 

1. Subjective assessment of nasal obstruction
   Subjective perception of nasal obstruction is clinically unreliable, as a considerable proportion of patients with objectively confirmed nasal narrowing do not report symptoms. In this context, the authors are encouraged to clarify why the subjective breathing pattern (oral vs. nasal) was selected as a variable and to explicitly state whether and how this subjective measure retains clinical relevance.
2. Potential impact of unperceived nasal obstruction on the study conclusions
   Given the high prevalence of unperceived nasal obstruction, it may be questioned whether misclassification of breathing pattern could undermine the validity of the study conclusions. The authors should address whether the presence of objectively significant but unrecognized nasal obstruction could challenge their interpretation and clarify why the main conclusions remain valid despite this limitation.
3. Clinical implications for treatment adherence (CPAP and oral appliances)
   Nasal obstruction—whether perceived or unperceived—has been reported to influence tolerance and adherence to CPAP therapy as well as to oral appliance treatment. The authors are encouraged to expand the Discussion to address the potential relationship between subjective breathing pattern, nasal anatomy, and treatment adherence, and to comment on possible clinical implications of their findings in this context.
4. Citation of Table 4 in the main text
   Table 4 presents important results regarding the anatomical localization of septal deformities in relation to breathing pattern; however, it is not explicitly cited in the main text. The authors should refer to Table 4 directly in the Results and/or Discussion section to ensure clarity and completeness.

Author Response

1. Subjective assessment of nasal obstruction Subjective perception of nasal obstruction is clinically unreliable, as a considerable proportion of patients with objectively confirmed nasal narrowing do not report symptoms. In this context, the authors are encouraged to clarify why the subjective breathing pattern (oral vs. nasal) was selected as a variable and to explicitly state whether and how this subjective measure retains clinical relevance.
Response: Thank you for your comments. Subjective assessment of nasal breathing was chosen because it provides insight into the individual perception of nasal patency and the presence of respiratory difficulties, which we consider an important aspect of the participants’ functional status. The subjective sensation of impaired nasal breathing does not always correspond completely with objective findings; therefore, subjective assessments have considerable clinical and research value, particularly in evaluating symptoms and their association with quality of life and daily functioning. For this reason, we decided to rely solely on subjective assessment. Based on your suggestions, I have incorporated the necessary revisions and explanations into the manuscript.

2. Potential impact of unperceived nasal obstruction on the study conclusions Given the high prevalence of unperceived nasal obstruction, it may be questioned whether misclassification of breathing pattern could undermine the validity of the study conclusions. The authors should address whether the presence of objectively significant but unrecognized nasal obstruction could challenge their interpretation and clarify why the main conclusions remain valid despite this limitation. Response: Thank you for this important comment. We acknowledge that objectively significant but subjectively unrecognized nasal obstruction may have resulted in some degree of misclassification. However, the primary aim of our study was to evaluate subjective perception of nasal breathing, which represents a clinically relevant outcome in its own right, rather than objectively measured nasal patency. Therefore, our conclusions relate specifically to perceived nasal obstruction and its association with OSA severity. Although the lack of objective nasal assessment is a limitation of the study, we believe it does not invalidate the main findings, which should be interpreted within the context of subjective symptom evaluation. Future studies incorporating both subjective and objective measures of nasal patency are warranted.

3. Clinical implications for treatment adherence (CPAP and oral appliances) Nasal obstruction—whether perceived or unperceived—has been reported to influence tolerance and adherence to CPAP therapy as well as to oral appliance treatment. The authors are encouraged to expand the Discussion to address the potential relationship between subjective breathing pattern, nasal anatomy, and treatment adherence, and to comment on possible clinical implications of their findings in this context.
Response: Thank you for this comment. Based on your suggestions, I have incorporated the necessary revisions and explanations into the manuscript.

4. Citation of Table 4 in the main text Table 4 presents important results regarding the anatomical localization of septal deformities in relation to breathing pattern; however, it is not explicitly cited in the main text. The authors should refer to Table 4 directly in the Results and/or Discussion section to ensure clarity and completeness.
Response: Thank you for this comment. Based on your suggestions, I have incorporated the necessary revisions and explanations into the manuscript.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

General comment

The manuscript has been substantially improved, and most of the previous concerns have been adequately addressed. The study is clinically relevant and well structured. I have only a few minor comments that may further improve the manuscript's clarity.

1. Language and typographical issues

Several minor typographical errors remain (e.g., “Discussion” is misspelled as “Disscusion”, “hypertrophied turbinate” appears as “hypertophied turbinate”, and “Morbis Popularibus” may require correction). A careful language revision is recommended.

2. Novelty statement

The statement about the lack of prior studies on subjective breathing patterns and OSA severity (e.g., “no studies” / “the first study” in the Discussion) may be somewhat overstated. The authors may consider slightly tempering this statement or providing additional support.

Author Response

Language and typographical issues Several minor typographical errors remain (e.g., “Discussion” is misspelled as “Disscusion”, “hypertrophied turbinate” appears as “hypertophied turbinate”, and “Morbis Popularibus” may require correction). A careful language revision is recommended.

Response: Thank you for your comment. I have corrected the spelling errors in the text. Regarding the titles De Morbis Popularibus and Morbis Popularibus, both forms are used equally in the literature. However, I have revised the text and used the title according to your recommendation.

Novelty statement The statement about the lack of prior studies on subjective breathing patterns and OSA severity (e.g., “no studies” / “the first study” in the Discussion) may be somewhat overstated. The authors may consider slightly tempering this statement or providing additional support.

Response: Thank you for your comment. I have omitted the stated sentence from the text.

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have adequately addressed all of my comments. I have no further concerns.