Chest X-ray at Emergency Admission and Potential Association with Barotrauma in Mechanically Ventilated Patients: Experience from the Italian Core of the First Pandemic Peak

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Congratulations to the authors for the results presented in the manuscript.

The contribution is interesting although not original given the number of similar observations present in the scientific literature.

The biggest problem with the validity of this research is the unavailability of the starting lung condition, before COVID, of each patient.

The limited availability of this data makes the final results less valid.

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

We do thank the reviewers for the comments. To the best of our knowledge there are studies comparing clinical Brixia results on CXR in the prediction of barotrauma. Moreover, we do understand and agree the reported biggest problem but, unfortunately, the starting lung conditions were not available since no previous CT o X ray studies prior to COVID infection were present and due to the emergency situation of the first pandemic peak. We added this point in limitation section of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

Your article ” Chest X-ray at emergency admission and potential value in predicting barotrauma in mechanically ventilated COVID-19 patients: experience from the Italian core of the first pandemic peak” is a well-written and balanced paper.

The selected groups of patients and the data analysis are accurate. The results of your teamwork have clinical importance in selecting the risk SarS-CoV2 group population in the development of barotrauma and assessment of the high risk of mortality.

After a close and conscientious reading of your paper, I concluded that this paper in the presented form meets the criteria for forward proceding in publication.

Author Response

We do really thank the reviewer for the comments and for considering the present manuscript suitable for publication.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors adress an important issue related to COVID critically ill patients- the prediction of barotrauma based on chest X rays, which are frequently performed when the patient with breathing insufficiency arrive in the emergency department/ICU.

there are some major concerns regarding methodology:

1. as this is a retrospective study, it is not predictive. Predictive scores can only be evaluated in prospective studies. here, we have a retrospective study that merely demonstrate an association between what was observed at presentation and the outcome in terms of barotrauma. the study should be rephrased from this point of view, starting from the title. It is "Association of brixia scroe with..."- thereafter, the authors could design a prospective study to investigate the predictive value. This also involves adequate methodology per STARD guideline, ROC curve analysis...

2. other factors influence the outcome and cannot be analysed here- the ventilation mode, asynchrony or dissynchronism during mechanical ventilation, sedation, cough efforts during cotnrolled mechanical ventilation, resistance and compliance, autoPEEP... thus, there are many confounding factors that should be analysed.

3. VILI is more related to large lung volumes during mechanical ventilation, favoring shear stress/rate, not barotrauma.

4. line 167- the authors have used the old definition of ARDS. Since 2012, Berlin definition stipulates severe ARDS as P/F ratio below 100.

5. please provide p-values for all statistical tests

In fact, a high Brixia scroe is related to disease severity and this is concordant to SOFA and number of mechanical ventilation days.

Comments on the Quality of English Language

moderate English corrections required

Author Response

REVIEWER #3

The authors adress an important issue related to COVID critically ill patients- the prediction of barotrauma based on chest X rays, which are frequently performed when the patient with breathing insufficiency arrive in the emergency department/ICU.

There are some major concerns regarding methodology:

1. as this is a retrospective study, it is not predictive. Predictive scores can only be evaluated in prospective studies. here, we have a retrospective study that merely demonstrate an association between what was observed at presentation and the outcome in terms of barotrauma. the study should be rephrased from this point of view, starting from the title. It is "Association of brixia scroe with..."- thereafter, the authors could design a prospective study to investigate the predictive value. This also involves adequate methodology per STARD guideline, ROC curve analysis...

Thanks for the comment. We emphasized repeatedly in the manuscript that the findings indicate an association rather than a causality indication. We also modified accordingly the manuscript title.

2. other factors influence the outcome and cannot be analysed here- the ventilation mode, asynchrony or dissynchronism during mechanical ventilation, sedation, cough efforts during cotnrolled mechanical ventilation, resistance and compliance, autoPEEP... thus, there are many confounding factors that should be analysed.

Thanks for the comment. We do agree with this possible influence; however, confounding factors could not be completely controlled in a retrospective study and specifically in this case also due to the emergency contingency. Again, we emphasized the associative nature of our results, without claiming causality prescriptions. Moreover, we highlighted this limitation in the discussion dedicated paragraph.

3. VILI is more related to large lung volumes during mechanical ventilation, favoring shear stress/rate, not barotrauma.

Thanks for the comment. We have eliminated the reference to VILI in the paper.

4. line 167- the authors have used the old definition of ARDS. Since 2012, Berlin definition stipulates severe ARDS as P/F ratio below 100.

We have changed the value in the paper according to your valuable comment.

5. please provide p-values for all statistical tests. In fact, a high Brixia score is related to disease severity, and this is concordant to SOFA and number of mechanical ventilation days.

Please note that p-values are reported as the last columns in tables 4 and 5.

Reviewer 4 Report

Comments and Suggestions for Authors

The purpose of the study was to evaluate retrospectively the Brixia score as a predictive score of barotrauma in COVID-19 patients in the ER setting. Although the aim of the study is interesting, there are major limitations which have to be mentioned.

Major comments:

1.            Is the aim of the study clear?

Firstly, the first aim to correlate risk of barotrauma with initial CXR findings is clear. However, the relationship between barotrauma and clinical and ventilator parameters is not given quite clearly.

2.            Is this a novel study?

 The study examines the prevalence of barotrauma during the first peak of COVID-19 pandemic. However, nowadays there is not such big concern in this aspect. Therefore, this study does not provide new knowledge and novelties in the readers.

Other comments to the authors:

 

1. Firstly, there is noted a quite important difference between the number of males and females included in the study which is associated with great inhomogeneity in the examined sample of population.

2. Moreover, the comorbidities of the patients included in the study are not showed.

3. There is no clear association between mortality and barotrauma in the text during ICU stay concerning the time of the death and/or survival after ICU admission.

4. In figure 4. the authors state in line 201 that <<the patient was alive at the end of the study..>>. However, there is no definition of the duration of the study.

5. The authors do not explain the finding of the similar mortality rate in the examined groups, in contrary of the literature.

Comments on the Quality of English Language

The text needs extended editing regarding English as past simple and present simple are confused throughout the text

Author Response

The purpose of the study was to evaluate retrospectively the Brixia score as a predictive score of barotrauma in COVID-19 patients in the ER setting. Although the aim of the study is interesting, there are major limitations which have to be mentioned.

Major comments:

1. Is the aim of the study clear? Firstly, the first aim to correlate risk of barotrauma with initial CXR findings is clear. However, the relationship between barotrauma and clinical and ventilator parameters is not given quite clearly.

Finding the correlation between barotrauma and ventilation parameters are not among the paper goals. However, they have been reported for the sake of completeness of the information.

2. Is this a novel study? The study examines the prevalence of barotrauma during the first peak of COVID-19 pandemic. However, nowadays there is not such big concern in this aspect. Therefore, this study does not provide new knowledge and novelties in the readers.

We do thank for the precise comment about our paper. We recognize that there are no direct specific novelties at this time point deriving from our results. However, in our opinion the main advantages of this study are: 1) a documentation of barotrauma incidence in the core of the first Italian pandemic peak; 2) a possible further block in the comprehension of COVID pathophysiology lung involvement; 3) a possible clinical-radiological model to assess this complication in other ARDS scenarios. To highlight these points, we rephrased the conclusion accordingly.

Other comments to the authors:

1. Firstly, there is noted a quite important difference between the number of males and females included in the study which is associated with great inhomogeneity in the examined sample of population.

We observed a higher incidence and worse outcome in males rather than in females in the total population of patients affected by covid 19 in our local regional area. This is correctly represented in the study. The reasons of this gender differences are beyond the purpose of the study and were therefore not investigated.

2. Moreover, the comorbidities of the patients included in the study are not showed.

The main comorbidities in the patients included in the study are: arterial hypertension (50.9%); diabetes (16.2%); ischemic heart disease (11.0%); peripheral vascular disease (8.7%); psychiatric pathologies (5.8%); rheumatological disease (4.6%); chronic obstructive pulmonary disease (4.6%); chronic renal failure (4.0%); peptic ulcer (3.5%); heart failure (2.3%). We did not report these data into the paper because they are not relevant and in order to not overload the paper with not relevant information. However, if reviewer and editor consider this point useful we will add it briefly in the manuscript.

3. There is no clear association between mortality and barotrauma in the text during ICU stay concerning the time of the death and/or survival after ICU admission.

Since this association was beyond the purpose of the study, therefore we did not investigate it and we focused our efforts in the described points and also according to the conclusion (please see answer to the comment above). Concerning the mortality rates, we decided to simply report those among the two groups (page 4, lines 157-159), without deepening analysis or discussion as many other factors, not predictable in a retrospective study, may influence in this clinical scenario patients’ survival.

4. In figure 4. the authors state in line 201 that <<the patient was alive at the end of the study..>>. However, there is no definition of the duration of the study.

No specific ending time point was reported in the manuscript. Please note that we considered from ER admission to ICU hospitalization, using as final timeline discharge or patient’s death.

5. The authors do not explain the finding of the similar mortality rate in the examined groups, in contrary of the literature.

We briefly discussed this point using the references proposed by the editor (Radiological-pathological signatures of patients with COVID-19-related pneumomediastinum: is there a role for the Sonic hedgehog and Wnt5a pathways? ERJ Open Res. 2021;7(3):00346-2021. Published 2021 Aug 23. doi:10.1183/23120541.00346-2021; Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study)  Pulmonology. 2022;S2531-0437(22)00260-4. doi:10.1016/j.pulmoe.2022.11.002).

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors adressed my main concerns- that this is an association study, retrospective analysis, not a predictive study. thus, conclusion now is different

Comments on the Quality of English Language

minor corrections

Author Response

We do thank reviewer for the approval.

Reviewer 4 Report

Comments and Suggestions for Authors

thank you for answering to my comments. I think there are no further questions to the authors.

Author Response

We do thank for the prompt and kind reply to our review.