Bidirectional Association between Psoriasis and Asthma: A Systematic Review and Meta-Analysis
Konrad Pazdrak
Round 1
Reviewer 1 Report
This intriguing review aimed to analyze prevalence of asthma among patients with psoriasis and the prevalence of psoriasis among patients with asthma through systemic search of the relevant (until March 2023) literature, first meta-analysis used data from 11 studies comprising >110K patients with psoriasis and 1.8 million control subjects. Major findings from the first meta-analysis were 1. The prevalence of asthma in patients with psoriasis was 9.2 with risk ratio (RR) 1.43, 2. Older (>50 years old) were significantly higher risk of (developing?) asthma and 3. Patients with moderate or severe psoriasis had higher risk of having asthma. Second meta-analysis used data from 3 studies on asthma patients (>468K) vs control subjects (>11 million) showing the prevalence of psoriasis in asthma patients was 1.3%. While there are several studies investigating comorbidity of psoriasis and asthma; the current review clearly indicates possible bidirectional association between psoriasis and asthma. This is significant contribution confirming earlier findings on asthma prevalence among psoriasis patients (Wang 2018) and extending it to significantly higher number of patients with similar stringent exclusion criteria. The strengths of this review include completeness of the literature analyzed, relevance to findings to developing preventative and therapeutic strategies for both diseases. It is also noteworthy pretty concise outline of molecular mechanisms of both diseases with indication of common pathways. However, phenotype of asthma was not included in the current analyses and therapies targeting IL-23/17 were disappointing likely due to high prevalence of TH2 high allergic phenotype of asthma suggesting next clinical trial should consider selection of patients with proper asthma endophenotypes (e.g ThH2 low). This omission of phenotyping asthma patients was cited as one of the weaknesses of this review and suggested future studies.
Minor comments: line 53 should be IL-23/TH17 axis.
Author Response
10th of May, 2023
Dear editors of the Journal of Respiration
Please find attached the original research article entitled “Bidirectional association between psoriasis and asthma: A Systematic Review and Meta-analysis” with all the addressed issues presented by the reviewers. Do not hesitate to contact me at [email protected] if you require any additional material.
Thanks for your time.
Sincerely,
Dr. Maria Ramos-Nino
Professor
Department of Microbiology, Immunology, and Pharmacology
School of Medicine, St. George’s University, Grenada, West Indies
Reviewer 1:
I highly appreciate the reviewer comments and time.
Line 53 has been corrected to IL23/Th17 (line 73)
Reviewer 2 Report
The authors present a well conducted study that provides insight into the bidirectional associations of psoriasis and asthma. Given that these are two common long-term health conditions, this is a topic that merits further investigation and better understanding. Furthermore any association between these 2 conditions could direct deeper study of potential shared molecular pathways. This is therefore a potentially important paper. Overall, the methodology utilised in this study is of appropriate quality and the paper is quite well written, albeit with some areas for improvement. There are a few points that need to be addressed to improve suitability to be accepted for publication.
Specific comments are listed below.
Comment 1: In the Introduction more detailed description should be made of the potential shared pathophysiological mechanisms for psoriasis and asthma. At present it conveys a message of Th1/Th17 driven psoriasis and Th2 driven asthma followed by a relatively brief exposition of IL-3/Th17 axis as a possible shared mechanistic path. However, the evidence for this pathway in asthma isn't well enough described in the Introduction and needs to be better outlined there. In that context, the Ostling UBIOPRED paper appears to be a seminal work that should be referred to: U-BIOPRED Study Group. IL-17-high asthma with features of a psoriasis immunophenotype. J Allergy Clin Immunol. 2019 Nov;144(5):1198-1213. doi: 10.1016/j.jaci.2019.03.027. Epub 2019 Apr 15. PMID: 30998987.
Comment 2: Introduction, the references seem to jump from 27 to 35. What happened to references 28 to 34 in relation to the Introduction? I note that these references appear in the Discussion. Please correct the referencing sequence as appropriate.
Comment 3: Introduction, Figure 1: The title appears to have merged with the main text (line 58). Please separate.
Comment 4: Introduction, Figure 1: Please add a Figure legend explaining all abbreviations.
Comment 5: Introduction, line 66: Presumably this should read IL-17 rather than IL-7? If so, please correct.
Comment 6: Methods, Section 2.2: Can the authors clarify whether there was any potential duplication or overlap of study populations between studies included in the systematic reviews? For example, in the current Table 2, there are 3 Danish studies which appear to have been conducted over a similar time period. Presumably sample overlap/ duplication was not an issue, but it would be appropriate to clarify that in the paper. If that cannot be excluded, then this should be raised in the limitations section of the Discussion.
Comment 7: Results, line 115-16, Table 1 and Table 2, section 3.2, lines 124 and 125: At present, I found the presentation of results somewhat confusing. Line 115 states that Table 1 shows meta-analysis for psoriasis vs control. Table 1 appears to show 3 studies and has a title of "Characteristics of the studies on the prevalence of asthma in psoriatic patients vs control". In line 124, the subheading is "asthma in psoriatic patients" but then in line 125 outlines that "a total of 11 studies....were included in the meta-analysis". Looking at the studies cited in Table 1, they appear to be studies of psoriasis prevalence in asthma. Conversely, studies cited in Table 2 appear to be studies of asthma prevalence in psoriasis. So should the current Table 2 actually be retitled as "Characteristics of the studies on the prevalence of asthma in psoriatic patients vs control" and repositioned as Table 1 while the current Table 1 is retitled as "Characteristics of the studies on the prevalence of psoriasis in asthma patients vs control" and becomes Table 2? If so, please amend the tables and descriptions in lines 115-116.
Comment 8: Results, section 3.3: In section 3.2 data are presented on subgroup analysis assessing impact of age, region and psoriasis severity for pooled risk of asthma severity. Were similar data available for the assessment of psoriasis-risk among asthma patients in section 3.3? This should be included if available or explained that appropriate data was lacking in these studies or highlighted as a weakness in the limitations.
Comment 9: The discussion is very brief and needs expansion in several areas to sufficiently explore some of the points that were raised by this paper and do the paper justice. At the moment this section doesn't really "discuss" the points but rather superficially highlights them. Areas that would benefit from more detailed discussion include:
i. How might the identified factors of age, ethnicity and disease severity mediate risk of this association?
ii. It would be helpful to discuss how each of the listed common risk factors in the 1st paragraph might mediate associations of psoriasis and asthma.
iii. The discussion of shared pathophysiological pathways is highly relevant, in particular the suggestion that the IL-23/Th-17 axis is important. The role of this axis in both psoriasis and asthma should be explored more deeply. As with the recommendation for the Introduction, specific focus on relevance to asthma should be revisited in the Discussion.
Author Response
10th of May, 2023
Dear editors of the Journal of Respiration
Please find attached the original research article entitled “Bidirectional association between psoriasis and asthma: A Systematic Review and Meta-analysis” with all the addressed issues presented by the reviewers. Do not hesitate to contact me at [email protected] if you require any additional material.
Thanks for your time.
Sincerely,
Dr. Maria Ramos-Nino
Professor
Department of Microbiology, Immunology, and Pharmacology
School of Medicine, St. George’s University, Grenada, West Indies
Reviewer 2:
Thank you for a detailed and insightful review. It has enhanced our paper enormously.
Comments and Suggestions for Authors
The authors present a well conducted study that provides insight into the bidirectional associations of psoriasis and asthma. Given that these are two common long-term health conditions, this is a topic that merits further investigation and better understanding. Furthermore any association between these 2 conditions could direct deeper study of potential shared molecular pathways. This is therefore a potentially important paper. Overall, the methodology utilized in this study is of appropriate quality and the paper is quite well written, albeit with some areas for improvement. There are a few points that need to be addressed to improve suitability to be accepted for publication.
Specific comments are listed below.
Comment 1: In the Introduction more detailed description should be made of the potential shared pathophysiological mechanisms for psoriasis and asthma. At present it conveys a message of Th1/Th17 driven psoriasis and Th2 driven asthma followed by a relatively brief exposition of IL-3/Th17 axis as a possible shared mechanistic path. However, the evidence for this pathway in asthma isn't well enough described in the Introduction and needs to be better outlined there. In that context, the Ostling UBIOPRED paper appears to be a seminal work that should be referred to: U-BIOPRED Study Group. IL-17-high asthma with features of a psoriasis immunophenotype. J Allergy Clin Immunol. 2019 Nov;144(5):1198-1213. doi: 10.1016/j.jaci.2019.03.027. Epub 2019 Apr 15. PMID: 30998987.
Answer:
The IL-23/Th17 pathway explanation has been broaden in the introduction and the reference suggested added.
Comment 2: Introduction, the references seem to jump from 27 to 35. What happened to references 28 to 34 in relation to the Introduction? I note that these references appear in the Discussion. Please correct the referencing sequence as appropriate.
Answer:
All references are accounted for. Some were part of the Figure 1 legend.
Comment 3: Introduction, Figure 1: The title appears to have merged with the main text (line 58). Please separate.
Answer:
Changes in the formatting has been changed to make Figure 1’s legend clear
Comment 4: Introduction, Figure 1: Please add a Figure legend explaining all abbreviations.
Answer:
The explanation of abbreviations has been added to the legend in Figure 1
Comment 5: Introduction, line 66: Presumably this should read IL-17 rather than IL-7? If so, please correct.
Answer:
Corrected to IL-17
Comment 6: Methods, Section 2.2: Can the authors clarify whether there was any potential duplication or overlap of study populations between studies included in the systematic reviews? For example, in the current Table 2, there are 3 Danish studies which appear to have been conducted over a similar time period. Presumably sample overlap/ duplication was not an issue, but it would be appropriate to clarify that in the paper. If that cannot be excluded, then this should be raised in the limitations section of the Discussion.
Answer:
The potential of duplication has been added in the discussion (lines 359-360)
Comment 7: Results, line 115-16, Table 1 and Table 2, section 3.2, lines 124 and 125: At present, I found the presentation of results somewhat confusing. Line 115 states that Table 1 shows meta-analysis for psoriasis vs control. Table 1 appears to show 3 studies and has a title of "Characteristics of the studies on the prevalence of asthma in psoriatic patients vs control". In line 124, the subheading is "asthma in psoriatic patients" but then in line 125 outlines that "a total of 11 studies....were included in the meta-analysis". Looking at the studies cited in Table 1, they appear to be studies of psoriasis prevalence in asthma. Conversely, studies cited in Table 2 appear to be studies of asthma prevalence in psoriasis. So should the current Table 2 actually be retitled as "Characteristics of the studies on the prevalence of asthma in psoriatic patients vs control" and repositioned as Table 1 while the current Table 1 is retitled as "Characteristics of the studies on the prevalence of psoriasis in asthma patients vs control" and becomes Table 2? If so, please amend the tables and descriptions in lines 115-116.
Answer:
There was an error and the Tables were introduced inverted. The Tables have been changed and the comments on lines 146-147.
Comment 8: Results, section 3.3: In section 3.2 data are presented on subgroup analysis assessing impact of age, region and psoriasis severity for pooled risk of asthma severity. Were similar data available for the assessment of psoriasis-risk among asthma patients in section 3.3? This should be included if available or explained that appropriate data was lacking in these studies or highlighted as a weakness in the limitations.
Answer:
It was clarified that the subgrouping in the metanalysis of psoriasis in asthma patients vs. control was not possible due to lack of data (lines 264-265)
Comment 9: The discussion is very brief and needs expansion in several areas to sufficiently explore some of the points that were raised by this paper and do the paper justice. At the moment this section doesn't really "discuss" the points but rather superficially highlights them. Areas that would benefit from more detailed discussion include:
- How might the identified factors of age, ethnicity and disease severity mediate risk of this association?
- It would be helpful to discuss how each of the listed common risk factors in the 1st paragraph might mediate associations of psoriasis and asthma.
iii. The discussion of shared pathophysiological pathways is highly relevant, in particular the suggestion that the IL-23/Th-17 axis is important. The role of this axis in both psoriasis and asthma should be explored more deeply. As with the recommendation for the Introduction, specific focus on relevance to asthma should be revisited in the Discussion.
Answer:
More comments and explanations have been added to the discussion
Submission Date
29 March 2023
Date of this review
30 Apr 2023 01:44:43
Bottom of Form
© 1996-2023 MDPI (Basel, Switzerland) unless otherwise stated
Round 2
Reviewer 2 Report
I'm grateful to the authors for addressing my comments and editing as requested. I think they have satisfied all the points that I highlighted and I'm happy to recommend publication.
