Immune Response and Exhaled Breath Profile Changes after Initiation of CFTR Modulator Therapy in Children with CF

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript delineates an immune response and exhale analysis among CFTR-modulator therapy in paediatric patients in a small-scale study. This data is interesting and may be useful at the clinical level.

The outcomes were lacking in exhaled analysis. Suggest adding more information and outcomes to this section to make it suitable for an Original Article type.

Major concerns.

1. Ethical consideration: Consider adding the Ethical statement to the Materials and Methods.

2. Participant's recruiting: Consider clarifying the city and country of the study site(s) and recruitment period (e.g. xxx Jan 2020 to yyy Mar 2021).

3. Exhaled breath analysis: This manuscript lacks exhale analysis data, including prominent/interesting substances.

Suggests adding more data on the exhaled compound to make it more information. 

Minor concerns.

1. Table 1: I think this table should summarise the overall of these participants with more parameters, including a subgroup analysis (e.g. Fisher's Exact or Chi-square) between responders and non-responders, to make it more informative.

The current version seems to have raw data. It should be used as a supplementary material. Otherwise, use it as Table 2.

 

Comments.

1. Abbreviations: Suggest sorting from A to Z to make it easy to read.

2. Was this project registered in any registry? (e.g. EU Clinical Trials Register)

If so, please clarify the registry and identifier for this project.
I know this study was not a clinical trial, but some studies can be registered in these registries.

3. Plots: Figures 1A and 1B in each column comprise various types of plots (square, triangular, cross, circle....). What does it mean?

I suggest using the same type of column to make it consistent.

4. Figures 2A, 3A and 3B: Suggest using a different type of plot (e.g. circle, square, triangular) in each subgroup to make it friendly for readers who print out with a monochrome printer.

5. Suggests adding the line number to make it easy to access a specific statement.

Author Response

Please see attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this study there are presented two possible approaches/methods for evaluating the possible response of  CF children treated with CFTR modulators. It is not clear how the study has been developed mainly regarding the controls. Authors dont specify who are the controls, it is not clear if they are healthy people or CF children not treated with Lumacaftor/Ivacaftor (page 3, line 3 and other points in the text). In my opinion the study should include healthy children versus CF and CF not treated patients vs treated CF in order to evaluate the role of Lumacaftor/Ivacaftor and its diagnostic value.  Authors have to clarify this point.

The introduction is quite confusing, please write with a logical development not jumping from a point to another. Some parts of it would be moved to the Discussion.

From Fig 1A it seems there are significant differences among the stimuli: if I understand well in the stimulus with Poly it seems to be much more active in decreasing the immuno response with respect to LPS, please comment

Fig 2: it would need a more detailed and comprehensive explanation

In the Discussion it is imporant to stress that authors are talking about trends and not statistically significant differences (page 8, three last lines). Moreover, also in the paragraph regarding the Barnaby studies it is needed to specify who are the controls 

 

Comments on the Quality of English Language

The language needs a revision

Author Response

Please see attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Comments.

1. Refer to the previous review comments. It seems not to address these minor concerns.

"Table 1: I think this table should summarise the overall of these participants with more parameters, including a subgroup analysis (e.g. Fisher's Exact or Chi-square) between responders and non-responders, to make it more informative.

The current version seems to have raw data. It should be used as a supplementary material. Otherwise, use it as Table 2."

 

2. Lines 285-292: all 18 discriminatory outcomes should be present in each time-point with a Table or Visualisation ( to make it easy to read and more informative.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Authors only partially responded to my previous concerns: the Introduction has been clarify with the descriotion of the objectives of the study. However they are not responding to my comment on the blood stimulation assay and on the exhaled breath analysis: what would the groups T0 and T1 represent? because there are not differences between responders and non-responders, even I will not understand there is a trend when you consider differences among them as in figure 3B

Discussion is still too long ( data from too much other studies not needed) and does not explain convincenly the results presented 

Comments on the Quality of English Language

Minor revision required of english text

Author Response

Please see the attachment

Author Response File: Author Response.pdf