Updates on Children with Allergic Rhinitis and Asthma during the COVID-19 Outbreak

Round 1

Reviewer 1 Report

The authors describe a questionnaire study looking at the impact the COVID 19 mitigation strategies have had on other respiratory disease such as asthma and allergic rhinitis in children.

1. Retrospective questionnaire study with 82/120 responding giving a 68% response so there may be some bias with recall and whether those in whom the disease had improved were more likely to respond.
2. Time frame is given as March to June for the lockdown – is this beginning of March to end of June i.e. 4 complete months
3. Was the questionnaire based on any other published questionnaire? And it should be submitted as supplementary material
4. Is there any electronic way of determining drug pick up rather than just asking families to recall
5. Was there one child pre family or more than one sampled
6. Figures: I don’t think figure 1 is useful as this is written in results and overlaps with figure 2. Similarly I don’t think figure 3 ad 4 are needed leaving just Figures 1 and 5. Also Figure 5 has ‘x’ and ‘y’ axes noted when the labels should be enough. Also is Figure 5 the best way of presenting this – it is hard to determine percentages as there are no measures or percentages in the figure.
7. Table 1: only the 0.05 confidence interval is needed in the legend – the other significance codes are not necessary.
8. The group that improved the least are those with house dust mite sensitization – but there is no interpretation of this in the discussion.
9. There are a couple of other papers that also looked at asthma - Lin CF et al, Frontiers in public health 2020  8 604089 showed no decrease in asthma presentations in a large hospital study despite decrease in respiratory infection, while Pelletier JH et al, JAMA Network open 2021 4 (2) e2037227 looking at trends in hospitalization across USA did show a reduction in asthma. Also trends for asthma hospitalisations in Japan Abe K et al, Journal of Allergy and Clinical Immunology in practice 2021 – so some comments from these papers would help discussion.
10. As well as some of the COVID 19 mitigation strategies – there is no mention about whether reduction in pollution that was seen in other countries could also have played a role in improvements here.

Minor edits:

• The numbers need adjusting – in the introduction 3.668.264 cases reported – the numbers need commas not full stops i.e. 3,668,264 And the numbers within the manuscript need adjusting this way.
• The font size changes in the manuscript towards the end of the introduction.
• In study design; not sure of the term ‘anamnestic data’
• In study design: should be ‘baseline use of drugs’ rather than ‘use of base drugs’
• The median ages just need to go to one decimal point. And p values could be just 2 or 3 decimal places with p<0.001 if lower (one p value goes to 9 decimal points).

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

• Some units of measurement are missing. In particular, in figure 1 (y-axis) and in figure 2 (right y-axis).
• Regarding the relationship between the type of sensitization and age, it would have been appropriate to perform a pairwise comparison between the groups given the significance of the ANOVA test
• Data on allergic sensitization of patients with asthma and allergic rhinitis who experienced worsening of symptoms are missing. It would be interesting to show them as it has been done for patients who have experienced improvement.
• The paragraph from line 147 to line 155 is unclear. In detail, it is not clear what the fisher test has been applied to and consequently it is not possible for the reader to interpret the described statistical significance. Also the sentence in lines 150-152 is repeated in lines 153-155.
• It would be useful to specify to which group of patients is referring the reduction of standard therapy for asthma and rhinitis expressed as a percentage in line 171.
• English language revision is highly recommended

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

General comment: The study was conducted on a relatively small group of patients. It is based on a subjective assessment of the improvement or worsening of symptoms compared to 2019. The credibility of such declaration is very limited. Moreover, all declarations were collected from parents and not from the patients (children) themselves. Most of these limitations were described by the authors themselves, however, they have a significant impact on the reliability of the results and the significance of the study.

Specific comments:

Introduction

Line 65-66. The aim of the study should be clearly formulated and described in the last section of the introduction.

Materials and methods

• Line 69-72 It should be emphasized here that the invitation e-mail was sent to the parents of the children. The actual respondents were parents.
• Information on the number of invitations to the survey and the response rate should be placed in this section, and not in the description of the results (line 109-110)
• Are there any inclusion / exclusion criteria for the study?
• Line 87. Information on the type of the study (retrospective study) should be included in the study design section, not Statistical analysis.

Results:

• Line 110. Do the authors really mean "median age" and not mean age? A value of 9.73 indicates that this is probably the mean, not the median. In the case of a normal distribution, using the mean is fully justified.
• Line 114. The p-value (p = 0.0491) should be described as p <0.05.
• Line 118. Graph description is incorrect. It shows the age distribution (box-plot) by the sensitization factor. Repeating the contents of the description in line 119-120. The same problem occurs in the descriptions of the other figures and tables.
• Line 122 (Figure 1). It is worth to add a description of the Y axis (AGE) in the chart
• Figure 2. It seems that the number of people included in the study is too small to present the results in this way.
• Figure 2. The Y axis should be described in %, which will make it easier to understand the figure.
• Line 130-131. I have no justification for presenting the results with an accuracy of .01 with n = 82.
• Figure 3 and Figure 4. Data can be presented in Figure 1 - bar chart cumulated up to 100%. It is advisable to add the number of respondents (analysis carried out in subgroups).
• Line 138-142. I have no justification for presenting the results with an accuracy of .01
• Line 149. Instead of (p = 0.006648406) there should be p <0.01
• Figure 5. No description of the Y axis.
• Line 164-171. I have no justification for presenting the results with an accuracy of .01
• Line 175. The 95% CI OR range indicates a non-significant result.
• Table 1. I have doubts as to the correctness of the analyzes carried out. OR should not be a minus value.

References
• Line 244. No data access date

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

This is a revised manuscript of a questionnaire study looking at the impact the COVID 19 mitigation strategies have had on asthma and allergic rhinitis in children. Thank you for making adjustments.

• Abstract conclusion: Just put results here without restating the study. ‘There was a general trend of improvement in asthma and allergic rhinitis symptoms with an associated reduction in the use of baseline and on-demand therapy.’
• Lines 43-48: given the ever changing numbers of COVID 19 positives and mortality – it would be better to give the date that you are quoting the figures from – perhaps corresponding to either the beginning of the end of the study period.
• In opening paragraph of study design add that the questions are in supplementary material.
• The dates are now given as beginning of March to beginning of June but only need to say this once.
• There is a lot of statistical analysis for a straight-forward investigation.
• The years of age and the percentages all should be to only one decimal place.
• Lines 132-138 – only need second part of this paragraph

Edits:

• Abstract Line 27: ‘between 6 and 16’ add ‘years’
• Abstract Line 35: ‘In addition, we registered a reduction…’ to ‘There was also a reduction…’ 
• Line 52: ‘results from a study conducted by Du H et al’ to ‘Du et al studying a cohort’
• Line 55: ‘that it could represent a protective condition’ to ‘ that allergy could be a protective condition’
• Line 70: ‘around’ to ‘approximately’
• Line 71: don’t need ‘asked them to answer the questions’ as you have stated that you sent them a questionnaire
• Line 106: add ‘years’ after ‘9.7’ & after 8.7 line 119
• Line 112: polisensitised’ should be ‘polysensitised’
• Line 131: ‘remnants’ better as ‘remainder’ which is what I think is meant  
• Conclusions: ‘a little exposure’ to ‘with less exposure’
• Conclusions: ‘a deeper cleaning’ to ‘possibly increased cleaning’

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

The authors complied with most of my comments.

My last comment was the fact that the references relating to online sources should be given with the details of the access, for example [Access: 05/13/2021].

58-62. In my opinion, the aim of the work is not properly described. Based on results and conclusions, it should be, for example, the impact of lockdown on the symptoms and use of medications in group of children sensitised to grass pollen and dust mite.

Line 73. Did the authors really mean Google Doodle and not Google Drive (as in the original version) or Google Forms?

General remark to the results: Presentation of results with an accuracy of .01% for a sample of 82 patients is not justified. With such a small sample, the estimation error is huge. Such presentation of the results gives the illusion of the accuracy, which is not reflected in the facts.

Line 115/116. The description of the figure is misleading. The figure shows the age distribution of the respondents depending on the type of allergy, and not sensitizations according to age.

Author Response

we have added the file below

Author Response File: Author Response.docx