-->PONE-D-25-36668-->-->Household air pollution is associated with disease severity in Ugandan children hospitalized with hypoxemic pneumonia-->-->PLOS One

Dear Dr. Hawkes,

Thank you for submitting your manuscript to PLOS ONE. Though the paper has been reviewed by several reviewers, the responses of the comments are still missing. Please provide the responses to the comments and re-submit the revised paper according the comments made by all the reviewers and indicating how and where the comments have been addressed. Additionally, you are requested address some fresh comments made by me as mentioned below. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.-->--> -->-->Academic Editor comments:-->-->:-->-->1. The authors needs to provide the function from which the PM2.5 exposures were made from household characteristics along with its vital information about the model used.-->-->.2.  Authors need to express the computational formula for the calculation of the sample size with input variable values. Only mentioning about the software is not appropriate.-->-->3, It needs to be clarified why non-parametric test was used instead of parametric test for measuring comparative statistics.-->-->4. It needs to be clarified how the odds ratios of different outcomes for risk factors were calculated along with their confidence intervals in the methodology section.-->-->5. I could not find the questionnaire for the SICK score calculation with reference. Please add it in supplementary.-->-->

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Srijan Lal Shrestha, Ph.D.

Academic Editor

PLOS One

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2.Thank you for stating the following financial disclosure:  [This study was supported by Grand Challenges Canada (Grant Number 1909-27795 [MH]) and The Women and Children’s Health Research Institute (Reference Number WCHSSLDRP 2371).].

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Reviewers' comments:

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1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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-->5. Review Comments to the Author

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Reviewer #1: This manuscript presents relevant information regarding the exposure to household (HAP) - and not traffic-related - air pollution and the sickness severity among Ugandan children. It is very impressive because Uganda is one of the many low- and middle-income countries that rely on biomass combustion for cooking, heating and lighting. This manuscript presents data from a noteworthy large sample size, 735 children from 20 hospitals, and convincing results and a very clear discussion. However, I still have some doubts on how they estimated the PM2.5 levels.

Here are some minor points that should be addressed before accepting this manuscript for publication.

Minor comments:

# We need more details about the PM2.5 data. Was it measured in µg or estimated, like an index? Describe it better.

-Lines 96-97: “We estimated the personal exposure of a young child to HAP using a log-linear model linking the kitchen concentration of PM2.5 to household variables [9].” Did you measure the PM2.5 concentration in the kitchens to estimate the real exposure? Mean measured PM2.5 should be presented in Table 2 too.

-Lines 101-103: “The ratio between the daily average personal exposure and kitchen concentration (0.628 for young children) was applied to estimate exposures for children in our study [10].” What exactly does this ratio mean? Explain better.

-“Statistically significant correlation between the PM2.5 and the SICK score (τ=0.15, p<0.0001). I cannot see this correlation in the graphic. What kind of variable was PM2.5 considered?

# Lines 282-284: “This estimate has a moderate correlation (r = 0.56) with measured values of PM2.5 [9]. This may have reduced the precision of the exposure assessment.” The R value of the correlation was already stated before, in the methods. So, you do not need to repeat it.

Reviewer #2: A. General Comments

This is a well-researched, logical, and highly consistent manuscript that addresses a critical gap in global health literature. While there is extensive literature linking household air pollution (HAP) to the incidence of pneumonia, this study provides significant additional value by focusing specifically on the severity and prognosis of pneumonia among a high-risk, hospitalized, hypoxemic cohort.

The large sample size (N=735) and the use of the validated "Signs of Inflammation in Children that Kill" (SICK) score provide a robust foundation for the authors' conclusions. The paper is written in excellent English and presents a compelling argument for HAP as a modifiable risk factor for pneumonia-related mortality.

B. Specific Recommendations for Improvement

1. Clarity on Clinical Assessment Timing (Lines 108–115)

The authors describe the calculation of the SICK score but do not explicitly state the timing of this assessment. While Table 1 suggests these were taken "at admission," the text should clarify if the SICK score represents a single baseline measurement upon hospital entry or a peak score during the stay. If it is an admission score, I recommend adding: "The SICK score was calculated upon initial hospital admission..." to line 111.

2. Magnitude of Association (Lines 182–187 & Figure 3A)

The authors report a statistically significant correlation between PM2.5 and the SICK score using Kendall’s tau (

τ=0.15. While this confirms a relationship, it does not provide a clinically intuitive sense of the effect size.

Recommendation: It would be highly valuable if the authors could provide a linear regression coefficient (β) to show the expected increase in SICK score points per unit (e.g., per 10 μg/m3) increase in PM2.5. This would allow clinicians to better understand the magnitude of risk.

3. Validity of the PM2.5 Modeling Approach (Lines 95–105)

The authors utilize a log-linear model to estimate exposure. While direct monitoring (e.g., personal samplers) is often preferred, the authors correctly argue that their quantitative modeling is more practical and "pragmatic" for a large-scale study in a resource-limited setting.

Recommendation: In the Discussion, the authors might briefly acknowledge that while the model has a moderate correlation (r=0.56) with measured values, it remains a superior alternative to simple dichotomous (Yes/No) fuel-type questionnaires, which are the standard in much of the existing literature.

4. Contextualizing Meta-Analysis Comparisons (Line 198)

The text mentions that the odds of pneumonia are 1.8 times higher in households exposed to solid fuels.

Recommendation: For clarity, please specify the comparison group used in this cited meta-analysis (e.g., compared to "clean-fuel households" or "non-exposed households").

5. Definition of the Multidimensional Poverty Index (MPI) (Table 1)

In Table 1, "MPI poor" is listed as a characteristic. The MPI is a complex composite index; the authors should briefly state the specific threshold or definition used to categorize a child as "MPI poor" in the footnote or Methods section to ensure reproducibility.

6. Formatting of Supplemental Material (Excel/CSV File)

Upon reviewing the supplemental data file, the data appears to be formatted as a raw CSV where all parameters are contained in a single comma-separated column (Column A).

Recommendation: To ensure the data is "Open Science" compliant and usable for other researchers, the authors should provide a properly formatted .xlsx or .csv file where each clinical and household variable is separated into its own clearly labeled column.

C.Conclusion

This study makes a strong contribution to the field by demonstrating that HAP is not just a risk factor for getting sick, but a driver of disease severity and mortality risk in children who are already hospitalized. The reasoning is sound, the limitations are honestly stated, and the clinical implications are clear. Following the minor clarifications above, the manuscript is well-suited for publication.

Reviewer #3: While reviewing the materials of the study, several questions and minor comments arose:

1. The study states that the average daily concentration of PM 2.5 is 145 μg per cubic metre. This is a rather dangerous concentration, as it is 10 times higher than the WHO standard. This is an important value for research, as it determines the prediction of risks to children's health. Therefore, it was necessary to clarify how this value was measured or calculated and to provide the calculation method or source for such a method.

2. The study should have listed the cities or towns in Uganda where the research was conducted. This does not violate the personal data of respondents but will allow for future analysis of data from the air pollution monitoring system on the streets of the studied areas to confirm that the health hazard to children comes specifically from the use of domestic stoves indoors.

3. It is known that stove heating and cooking are still used in many rural homes without centralised gas supply, including in Eastern European countries. However, carbon monoxide, which is produced by the incomplete combustion of organic fuel, is traditionally considered the main threat to residents there. In this regard, it was also worth describing the typical models of stoves used in Ugandan households.

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Reviewer #1: No

Reviewer #2: Yes: Thomas C. Carmine MD

Reviewer #3: Yes: Buchavyi Yurii

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Submitted filename: Review - HOUSEHOLD AIR POLLUTION .docx

Household air pollution is associated with disease severity in Ugandan children hospitalized with hypoxemic pneumonia

PONE-D-25-36668R1

Dear Dr. Hawkes,

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,

Srijan Lal Shrestha, Ph.D.

Academic Editor

PLOS One

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