Review Reports - HIPTox—Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology: A Single-Centre Double-Blind Human Exposure Trial Protocol

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Comments for author File: Comments.pdf

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Comments to the Authors:

In general, it seems to be proposal of project at first stage not completed work. It is very weak, not clear, no results, and no conclusion.

Abstract:

Abstract is clear, but authors wrote “Participants will all undertake five sequential” and “pollutants will allow”. I think all must be in past not future.

Introduction:

In line 79: authors wrote “1.3. Trial Design”. It should be transferred at the begging of materials and methods part.

Materials and Methods

In general, each part in materials and methods needs reference. Authors must be clarifying what was done in the current study. They should be writing about their work in study (in past sentences not future).
In line 88: authors wrote “The HIPTox study will be carried out at the NIHR/Wellcome”. It should be in past sentence.
In lines 96-97: authors wrote “The study is currently ongoing, and data collection is expected to be completed by the end of 2023”. What is that mean? How paper will be reviewed and the study is still currently ongoing and not completed “according to author’s words”?
In page 4: what is the important of “Table 1. Study time schedule of enrolment, exposures” in this study? It is important only for project proposal at the beginning of project, not at the end.
In lines 98-107: not clear. How can you use calculation method without reference? May be it correct or not, how can you confirm that?
In line 128: authors wrote “Participants will be recruited”. It should be in past sentence.
In lines 128-136: authors wrote “Participants will be recruited from the general public. Potential volunteers who are employees at The University of Manchester or Manchester University NHS Foundation Trust may take part if not involved with the project. Advertisement posters will be placed in any public spaces including trust and university buildings with contact details of the research team on; interested participants will be able to contact for further details. Social media advertisement using official accounts of the University of Manchester, NHS Manchester Foundation Trust, dementia charities, local community groups, and places of worship. We will also contact participants who have previously given permission to be contacted for research studies”. Which of the above done in study? Authors must be clarifying that.
In lines 146-147: authors wrote “Those responsible for data collection are MCRF staff, Dr Thomas Faherty, and Dr Huda Badri.” what is the important of that in text?
In lines 148-145: not clear. What was done in study? Authors must be clarifying that.
In lines 156-163: not clear. What was done in study? Authors must be clarifying that.
In lines 189-205: authors wrote “The four chosen pollutants have been selected”. These not pollutants but it are sources of pollutants.
In line 206: authors wrote “Participant exposures will be conducted”. It should be in past sentence.
In lines 212-214: authors wrote “Please see the Centre for Atmospheric Science webpage [40] and the following paper [41] for comprehensive details”. References only after sentence are enough.

Results

There are no results.

Discussion

Not clear.

Conclusion

There is no conclusion.

References

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Overview:

The authors present a protocol for a randomized human exposure trial in which recruited participants will sequentially receive four exposures (and one control) to airborne toxicants, have biospecimens collected pre- and post-exposure, and have various functional endpoints assessed, including cognition.

The amount of data to be collected during this study is certainly ambitious, as the authors noted in the discussion, which likely hindered their ability to recruit the originally intended study sample of 40 participants (now aiming for 15). The comments below are aimed at improving clarity.

Comment #1. More information about the four exposures in the Methods section would be greatly appreciated. As examples, which cleaning products will be used to generate the secondary organic aerosols exposure? What compounds are expected to be in the cooking aerosols exposure? These are just example questions and not an exhaustive list of what should be included in the section on these exposures.

Comment #2. Are there attempts to recruit approximately equal amounts of biological males and females in this study? Many exposures have sex-dependent effects, and therefore a statement on whether biological sex was considered during recruitment, or will be considered in analyses/future work, is warranted.

Comment #3. In the discussion, the authors state that this study will hold the potential to inform policy refinement. While this is likely true, to some extent, it seems that a study of 15 individuals will hardly be sufficient in informing policy. However, this study will certainly be informative for future, larger studies that are perhaps more targeted (once this study shows which exposures and endpoints to focus on). Some greater discussion of how this study will inform policy on its own, and how this study will inform future work, is needed in the discussion.

Comment #4. I may have missed this somewhere, but how does one standardize the amount of exposure respirated by the participant? I see details about the standardization of exposure concentration being emitted, but is there any post-hoc adjustment for breathing rate and/or body size of the participant (as a proxy for lung size)? There could be considerable variability in the amount of exposure uptake by participant, so some greater discussion of this (and how it is or is not a problem) is needed.