PONE-D-20-27227

Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: A systematic review of the literature and meta-analysis.

PLOS ONE

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Reviewer #1: Partly

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Reviewer #1: I Don't Know

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Reviewer #1: Yes

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Reviewer #1: No

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5. Review Comments to the Author

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Reviewer #1: The author performed a systematic review and a meta-analysis about ASA desensitization and the course of asthma in NERD. The authors wanted to assess the impact of ASA desensitization on FEV1, exacerbation rate and inhaled or systemic CSO use.

This is an interesting area though with scare reliable datas. Thus, I wonder wether a meta-analysis is the good choice for assessing the issue.

I have several concerns about this manuscript :

1°) Introduction :

General comment : this section is far too long and should be more synthetic.

line 79 to 86 : I recommend to compare with more recent datas from asthma European cohorts.

line 104 to 114 : references are needed in addition to the one quoted.

line121-122 : skin symptoms is urticaria.

line 126-140 : it should be appropriate to talk about respiratory ASA provocation test. Do they have a place for the diagnosis of NERD ?

line 143 : please mention molecules concerning strong COX-1 inhibitors

line 149 to 151 : please compare with more recent datas from asthma European cohorts.

line 167 : The authors cannot talk about tolerance to ASA since it implies a persistence of the effect after ASA cessation...this is not demonstrated and/or reported to my knowledge.

line 200 to 205 : please precise to the cell type

line 203 : wrong typo "downward" => down-regulation

line 211 to 216 : bette to say that AD is considered as an add-on therapy ?

line 242 to 246 : I'm not sure the authors can say that AD could replace biologics. Furthermore, I fear this assumption is out of the scope of the review.

2°) Method

General comment : this section seems to be rather well-written with regards to my limited knowledge in meta-analysis methodology.

line 335-336 : I do not understand the meaning of that sentence. The author should rephrase it.

3°) Results

General comment : this section is far too long. It should be re-organized in order to highlight important results and give a clear answer to the primary and secondary objectives.

Table 2 should be put in supplemental datas.

line 561 : Watch out typo the lead to misunderstading "but not the one by(...)"

4°) Discussion

General comment : this section should be re-written comparing AD benefits that were demonstrated in upper airways to AD benefits on lower airways.

line 568 to 604 : it sounds like results rather than discussion.

line 606 ti 674 : it sounds like method rather than discussion.

English should be reviewed by an English-native.

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Reviewer #1: Yes: Luc Colas

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Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: A systematic review of the literature and meta-analysis.

PONE-D-20-27227R1

Dear Dr. Fernández-Trujillo,

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

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Kind regards,

Christophe Leroyer

Academic Editor

PLOS ONE