PONE-D-19-25470

Prevalence and burden of bronchiectasis in a lung cancer screening program

PLOS ONE

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I commend the authors on the analysis of a large data set to evaluate the prevalence of bronchiectasis and related findings. In the related analysis of bronchiectasis and nodules, there are a few important adjustments/edits that would make the analysis more powerful and useful.

Major edits:

-Although there is reference to the screening protocol, it would be helpful to outline what is considered "positive."

-Current standard of care by 2D measurements, which is done in the US (Europe is using more volumetrics), includes a "positive" scan as > or = 6 mm. It appears the analysis was done with 5mm, which seems like a small difference but will alter the numbers, particularly when discussing "false positive." This paper will be referenced for "false positive" but will not be accurate for the current era if using an outdated definition of "positive." It would improve the analysis tremendously to use the updated definition of "positive."

-Care must be taken with analysis of impact of bronchiectasis within a screening program as the number of cancers is low. As part of this topic, the screening program includes those with a lower risk than those who qualify for screening in the US (starting age 40 with just 10 pack years. This can significantly impact the screening outcomes that does not make the generalizable to the currently qualifying population. If it is possible to separate out the population of those > or = 55 yrs old and pack years > or = 30 to determine if the numbers significantly change. (at a minimum it is important to acknowledge this difference from the currently approved lung screening population as publications like this get referenced to represent expectations within a lung screening program). This is important as "false positive" is something generally being overstated within lung screening programs and is getting broadly confused. This makes it even more important to be very clear about any false positive analysis. Line 308, "the number of subjects with new nodules during follow-up was 15% and 7% for individuals with and without bronchiectasis": What is considered "new nodules"? Does this mean a positive nodule of at least 5 mm? Or does this mean any nodule? The overall analysis of bronchiectasis and lung screening analysis could be more clear.

I do not see all the data from the analysis.

Reviewer #2: This is an important topic and I believe the presence of bronchiectasis does increase false positives. Most of my comments are related to clarity of writing and data presentation.

Do you have an estimate for Power to detect difference between these groups (i.e. cancer incidence)?

Line 138 do you mean to say that controls were matched on these variables?

Table 3A: recommend using parallel phrases as described in text. E.g. nodules that do not meet criteria for further tests; nodules requiring additional tests (false positives); lung cancer (true positives)

Table 4. Regression analysis to assess appearance of false positives on baseline and follow-up studies. Suggest rewording title to be more descriptive “relationship of variables with false positive nodules”

Might be helpful to describe what if any guidelines used for follow up, antibiotics or indicate that testing was done, antibiotics were prescribed, if at the discretion of treating provider or local study team (example, as in line 226 “an indication for antibiotics”)

Table 3 comes after Table 4 and has unclear text and formatting:

Why is there a “B” without an “A” label? Perhaps a formatting error?

Unclear what this means “Growth nodules but do not require additional tests” a growing nodule that didn’t undergo additional testing? That would not be typical

Line 303 – most reports of annual compliance in the US at least, are lower than what the authors report and even lower than what was seen in this study

Line 317 – not sure what conclusion you are drawing here (patients with bronchiectasis should not be screened?)

Line 325 the summary here seems to differ from what is shown in Table 3B. Is table 3A missing (showing prevalence)

Line 363 suggest adding qualifier for bronchiectasis to improve clarity, for example: “the degree of this limitation is also correlated to with the radiographic severity of bronchiectasis” to be more clear

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Reviewer #1: No

Reviewer #2: No

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Prevalence and burden of bronchiectasis in a lung cancer screening program

PONE-D-19-25470R1

Dear Dr. Sánchez-Carpintero Abad,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Peter M.A. van Ooijen, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: line 325 appears to have the incidence and prevalence values reversed.

Author response in reference to question about what is considered "new nodules" in initial line 308 provides quote "Newly identified solid or part-solid nodule < 3.0 mm or nonsolid nodule of any size." I do not see this in the text. The edit to lines 123 and 132 do not make it more clear what is considered a "new nodule". The quoted text provided in the author answer could be included if this is accurate. It would strengthen the paper to specify more explicitly how the nodules are being categorized.

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Reviewer #1: No