Evolving Concepts in Progressive Pulmonary Fibrosis: A Clinical Update

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript titled- Evolving Concepts in Progressive Pulmonary Fibrosis: A Clinical Update by María Belén Noboa-Sevilla discussed the limitations of current evaluation methods and potential solutions, focusing on the importance of validated tools to assess symptom variation, standardization of lung function measurement methods, and improvements in quantitative radiological assessment. 
The manuscript addresses a timely and relevant topic, PPF, a clinically meaningful and increasingly recognized phenotype in Fibrosing interstitial lung diseases. 

Although the authors address the importance of PPF worsening of symptoms, decline of lung function, and radiological progression, helping clinicians grasp the complexity of diagnosis and management. Authors critique existing diagnostic procedures, highlighting limitations. 
However, the manuscript needs improvement in certain sections.
The manuscript presents current knowledge, but lacks new hypotheses, integrative models, or original interpretations that would elevate it beyond a literature summary. 
Depth in the radiologic section should be deeper. 
Please cite more updated articles if available. 
Please revise for grammatical corrections. 
In the conclusion, Current challenges in PPF diagnosis and management include 1.  The need for validated tools to objectively assess symptom progression. 2. Standardization of lung function measurement methods and interpretation. 3. Development of more reliable and reproducible quantitative CT analysis techniques. 4. Establishment of optimal follow-up intervals for radiological assessment.
 the text would more harmonized to use text format for 1 (first) 2(second and 3 (third) and 4 (forth) 

Author Response

 

Response to Reviewer Comments

We sincerely thank the reviewers for their time, constructive comments, and insightful

suggestions. Below, we provide detailed, point-by-point responses and indicate the

corresponding revisions made in the manuscript.

Reviewer 1

Comment 1: The manuscript presents current knowledge, but lacks new hypotheses,

integrative models, or original interpretations that would elevate it beyond a literature

summary.

Response:

The Introduction has been expanded to incorporate a comprehensive conceptual framework

for progressive pulmonary fibrosis (PPF). An integrative approach—encompassing

standardized symptom assessment, optimized functional thresholds, and advanced

imaging—is proposed to enhance early diagnosis and therapeutic decision-making across

diverse ILDs. This perspective summarizes existing knowledge and also presents a

hypothesis and conceptual model to guide future research and the development of clinical

tools.

(Pages 1–2, lines 38–118)

Comment 2: Depth in the radiologic section should be deeper.

Response:

The radiologic section now addresses:

• Limitations of HRCT, including interobserver variability, lack of standardized

thresholds for progression, and challenges in differentiating subtle fibrotic changes.

• Established prognostic features, such as honeycombing, traction bronchiectasis, and

lobar volume loss, highlighting differences between IPF and non-IPF ILDs.

• Emerging quantitative and AI-driven imaging techniques that provide reproducible

metrics while noting current limitations in accessibility and validation.

(Page 6, lines 191–207)

Comment 3: Please cite more updated articles if available.

Response:

Recent studies from the last 2–3 years have been incorporated to ensure the manuscript

reflects the current state of knowledge.

Comment 4: Please revise for grammatical corrections.

Response:

The manuscript has been carefully revised for grammar, clarity, and style throughout.

Comment 5: Harmonize the conclusion numbering.

Response:

The conclusion has been revised as follows:

1. The need for validated tools to objectively assess symptom progression.

2. Standardization of methods for measuring and interpreting pulmonary function.

3. Development of more reliable and reproducible quantitative CT analysis techniques.

4. The establishment of optimal follow-up intervals for radiological evaluation.

(Page 7, lines 539–543)

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The article requires a few minor improvements before final consideration of publication in this journal.

1. The hypothesis of the study should be mentioned in the last segment of the introduction forum.
2. The authors should create a discussion forum separately. 
3. The authors should enrich the introduction forum. Please include a few lines in the introduction section.

Author Response

Response to Reviewer Comments

We sincerely thank the reviewers for their time, constructive comments, and insightful

suggestions. Below, we provide detailed, point-by-point responses and indicate the

corresponding revisions made in the manuscript.

Reviewer 2

Comment 1: The hypothesis of the study should be mentioned in the last segment of the

introduction.

Response:

The final segment of the Introduction now explicitly states the study hypothesis: an

integrative approach to PPF—encompassing standardized symptom assessment, optimized

functional thresholds, and advanced imaging—may enhance early diagnosis and therapeutic

decision-making, supporting the development of future clinical tools and research

strategies.

(Page 2, lines 108–113)

Comment 2: Create a separate discussion section.

Response:

A dedicated Discussion section has been added (Section 5, page 7, lines 223–245). Key

points include challenges in symptom, functional, and radiological assessment; a proposed

multidimensional framework integrating patient-reported outcomes, functional thresholds,

and AI-assisted imaging; heterogeneity across ILD subtypes; and future directions for

personalized care.

Comment 3: Enrich the Introduction.

Response:

The Introduction now emphasizes real-world challenges in applying PPF definitions,

particularly in non-specialized centers, and highlights how integrating recent evidence with

practical insights supports clinicians in diagnosis, follow-up, and therapy.

(Page 2, lines 56–60)

Reviewer 3 Report

Comments and Suggestions for Authors

Title of Manuscript: Evolving Concepts in Progressive Pulmonary Fibrosis: A Clinical Update
Manuscript Type: Perspective
Journal: J. Respir. 2025

Overall Assessment

This manuscript offers a timely and well-organized clinical perspective on the evolving definition, diagnosis, and challenges associated with Progressive Pulmonary Fibrosis (PPF). It provides an updated summary of current clinical criteria, highlights existing limitations in the application of these criteria, and points to directions for future improvements. The writing is clear, and the structure facilitates understanding. However, some aspects require deeper discussion and minor revisions for clarity and impact.

Major Comments

1. Originality and Significance
Strength: The focus on PPF as a unifying phenotype across ILDs, shifting from etiology to disease behavior, is clinically significant.
Suggestion: The authors could better highlight how their clinical perspective fills a current gap, e.g., unmet needs in daily practice or areas where guidelines are still ambiguous.

2. Scientific Depth and Balance
The discussion of functional vs. radiological vs. symptomatic criteria is comprehensive.
Recommendation: Deepen the analysis of real-world challenges in applying the PPF criteria in community settings vs. academic centers. Are there disparities in implementation?

3. Use of Evidence and References
The paper includes an impressive selection of recent high-quality studies and guidelines (e.g., ATS/ERS 2022, INBUILD trial).
Some references could be expanded into tables or comparison summaries to better highlight the evolution of definitions (e.g., pre-2022 vs. current criteria).

4. Figure and Table Interpretation
Figure 1 and Table 1 are relevant.
Comment: Improve labeling and resolution of Figure 1. Consider adding annotations or summary boxes to guide the reader through radiological changes.
Suggest including a figure comparing absolute vs. relative FVC declines with outcomes, to complement the textual explanation.

5. Critical Appraisal of Criteria
The manuscript recognizes that symptom-based assessment is limited by subjectivity.
Enhancement: Offer potential validated patient-reported outcome measures (PROMs) or future digital tools under investigation that may bridge this gap.

6. Language and Clarity
The writing is mostly fluent and precise.
A few grammatical issues and run-on sentences in sections 2 and 3.3 should be edited for clarity. Minor copyediting needed throughout (e.g., “CVF” should be “FVC”).

Minor Comments

Line 44: Consider revising “PPF a term that describes…” → “PPF is a term that describes…”

Line 82: Reword “this parameter is challenging to evaluate systematically” to “this criterion remains difficult to assess in a standardized manner.”

Line 124–126: The authors should avoid suggesting that the relative method is always superior without noting its potential overestimation risk in milder disease.

Line 186–188: The concluding paragraph would benefit from clearer examples of how PPF concepts have directly impacted therapeutic decisions.

Recommendation

Recommendation: Minor Revision

The manuscript provides a valuable clinical synthesis and is suitable for publication after addressing the above comments. Clarifying some methodological nuances, refining figures, and improving the narrative flow in a few sections will enhance its impact and clarity for a broad clinical audience.

Author Response

Response to Reviewer Comments

We sincerely thank the reviewers for their time, constructive comments, and insightful

suggestions. Below, we provide detailed, point-by-point responses and indicate the

corresponding revisions made in the manuscript.

Reviewer 3

Comment 1: Highlight how the clinical perspective fills a current gap.

Response:

The manuscript emphasizes disparities between academic centers and community settings

in implementing PPF criteria. Simplified, reproducible tools and collaborative networks are

proposed to enhance guideline adherence and patient outcomes.

(Page 8, lines 246–259)

Comment 2: Deepen analysis of real-world challenges.

Response:

The discussion now details how academic centers, with multidisciplinary teams and

structured follow-up, can consistently implement PPF criteria, whereas community

practices face limitations in imaging, pulmonary function testing, and access to

antifibrotics, highlighting the need for simplified tools and collaborative networks.

(Page 8, lines 260–270)

Comment 3: Use of evidence and references; expand into tables.

Response:

Table II has been added to summarize the evolution of PPF diagnostic criteria pre-2022

versus the 2022 ATS/ERS/JRS/ALAT guidelines, covering definition, observation period,

symptoms, pulmonary function, imaging, minimum criteria, clinical application, and

therapeutic implications.

(Page 6, lines 213–215)

Comment 4: Improve figure and table interpretation.

Response:

Figure 1 resolution and labeling have been improved with annotations and summary boxes.

Table 1 now illustrates absolute versus relative FVC decline, complemented by a graphical

representation for clarity.

(Pages 4–5, lines 119–169)

Comment 5: Include PROMs and digital tools.

Response:

The manuscript now references validated PROMs (e.g., K-BILD questionnaire) and

emerging digital tools (e.g., wearable trackers, home spirometry) to complement the

proposed multidimensional scoring system for PPF, guiding earlier treatment decisions.

(Page 7, lines 216–222)

Comment 6: Language and clarity issues.

Response:

Grammar, clarity, and scientific writing have been revised throughout, including correction

of “CVF” to “FVC.”

Comment 7: Revise “PPF a term that describes…”

Response:

Updated text: “PPF is a term that describes pulmonary fibrosis that continues to progress—

despite optimal therapy—regardless of the underlying cause.”

(Page 2, lines 121–122)

Comment 8: Reword “this parameter is challenging to evaluate systematically.”

Response:

Updated text: “This criterion remains difficult to assess in a standardized manner.”

(Page 3, line 204)

Comment 9: Avoid suggesting relative method is always superior.

Response:

Updated text: “It should be considered that the assessment in patients with preserved lung

function or with mild alteration could be underestimated using this method.”

(Page 4, lines 336–338)

Comment 10: Clarify examples of therapeutic impact of PPF concepts.

Response:

The PPF framework has guided earlier use of antifibrotics in non-IPF ILDs, prompted

tighter monitoring, and improved outcomes by preventing irreversible lung damage.

(Page 8, lines 574–584)