CO2 Laser Photoacoustic Spectrometer for Measuring Acetone in the Breath of Lung Cancer Patients
Round 1
Reviewer 1 Report
In the manuscript, the authors present a study regarding the detection of acetone in the breath of patients with lung cancer using a laser photoacoustic method. They included in the study 30 subjects (11 patients with lung cancer, 9 patients with other lung diseases and 10 healthy subjects). In my opinion it is an interesting study that can be published. In order to improve the quality of the manuscript, some changes of the manuscript have to be done. My observations are :
- Please include in the manuscript some data regarding the incidence of diabetes mellitus in the subjects that were included in the study. Also is important to specify if the subject that were included in the study, were suffering from some inflammatory disorders that could influence the results of the study.
- Please include in the discussions part of the manuscript some data regarding the limitations of the study.
- Please reorganized the abstract (introduction, methods, results, conclusions)
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors present a photoacoustic spectroscopy method for analysis of low concentrations of VOCs, and validate this using patients breath. Overall this is an interesting study, although I am not certain about the validity of the study that aims to use the system to quantify compounds on patients breath. It is not clear what the rationale is for using the system to detect these three compounds on the breath of lung cancer patients (except that it is a real world application). With that in mind I would have been happier if the authors simply developed the system and validated it in the real world on the breath of asymptoamtic patients. It is useful to understand the levels of compounds on the breath of asymptoamtic individuals, and the effectivenes of this method in quantitation vs. another method such as SIFT-MS/GC-MS or another method. This would provide a good validation of the developed system without claiming some effectiveness for disease diagnosis, especially where a marker such as acetone is so ubiquitous and variable on the breath of healthy humans. So that is my main criticism of the study, that claiming disease diagnosis maybe undermines the fundamnetal aspects of the work.
The abstract could mention the patient numbers used in each groups if the disease diagnosis part is to be kept.
Not sure that an ethics statement is required in the abstract beyond other information that is required.
THe introduction has a few opening sentences outlining the need for detection systems, but there are no references associated with this text. Also this text does not give a very clear overview of the need ffor sensor systems and associated applications.
There are a few sentences on GC-MS and its limitations, but again these are not referenced appropiately.
There is a paragraph on acetone. It may be useful to outline some SIFT-MS/PTR-MS studies which have been carried out on large populations of healthy people of different ages. The ranges measured in healthy individuals could be added to the introduction in addition to outlining the conflicting evidence of acetone linked to disease.
Materials and methods -not sure a description of the PAs technique itself is required at the beginning of this section, it could be in the Introduction if considered important enough.
Having 30 patients in a disease diagnosis study focussing on measuring a very common compound such as acetone is not really enough. If we consider that every group has approximately 10 people and that this is a 3 way problem i.e. lung cancer group/healthy control and lung disease other than lung cancer. I would say that this study is not really adding anything to the validation of the system in real world applications. A study of as many healthy individuals may have been just as valid, ideally as many individuals as possible vs. a benchmarking technique.
The results section is good interms of the validation of the sensor and rationale for the measurement. The weakness is the disease diagnosis section and discussion surrounding that. But the authors do at least acknowledge that Acetone has no validity as a biomarker based on this and previous studies. It might be better to concentrate on methods that do require a measurement of acetone, such as screening for undiagnosed diabetes etc. monitoring dietary interventions. It is also important to discuss the reasons for detecting ammonia/ethylene on breath and other applications of the sensor. It would be good to pay this as much attention as acetone.
In conclusion, I think part of this manuscript is publishable, but the empahsis from disease diagnosis is the most important change as currently this reduces the significance of the work, rather than enhancing it.
Author Response
Please see the attachment
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
In the manuscript, the authors present a study regarding the utility of the CO2 laser photoacoustic spectrometer for the detection of acetone in the breath of the patients with lung cancer. In my opinion it is an interesting manuscript that can be published. The manuscript has been reviewed before and the authors changed the manuscript according to the previous reviewers indications. Their comments are pertinent. That is why, I think that this manuscript can be published in this form.
Reviewer 2 Report
The authors have made substantial efforts to address my comments and have taken on board the major comment about the fundamental aspects of the study and how this should be emphasised vs. the disease diagnosis part. In my opinion it is an interesting paper and worthy of publication.
