Epidemiology Article Critique: Ambient Temperature and Air Pollution

This report presents a critical appraisal of an epidemiology article titled, 'Acute effects of ambient temperature and particulate air pollution on fractional exhaled nitric oxide: A panel study among diabetic patients in Shanghai, China.' The report examines the research question, study design (longitudinal panel study), participant selection, potential errors, biases, confounding variables, hierarchy of evidence, ethical considerations, and statistical and clinical significance. The study investigated the association between ambient temperature, particulate matter, and respiratory inflammation (nitric oxide) in type 2 diabetes patients. The report discusses the study's validity, potential publication bias, and strengths and weaknesses of the research methodology. The analysis highlights the importance of considering factors like sample size, confounding variables, and ethical considerations in epidemiological studies. The report concludes with an assessment of the study's statistical and clinical significance, emphasizing the impact of environmental factors on respiratory health and the need for further research in this area. The report also mentions the potential for publication bias and the importance of internal and external validity in the study's findings.

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Fundamentals of Epidemiology
Name
Date of Submission

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This is a critical appraisal of an article titled, ‘Acute effects of ambient temperature and
particulate air pollution on fractional exhaled nitric oxide: A panel study among diabetic patients
in Shanghai, China’, written by Li H, Bai H, Yang C, Chen R, Wang C, Zhao Z, Kan H., and
published in the journal of epidemiology, 27(12):584-9, in the year 2017.
1. Research questions
The research question being answered in this article is concerning the mechanisms involved in
the air pollution by particulate matter in presence of ambient temperatures 1. To do this therefore,
the researchers determined the association between fine and coarse particulate matter, and
ambient temperatures during the fractional exhalation of nitric oxide, which is a biomarker of
respiratory inflammation 2. This research question is valid and in line with the topic because the
authors have linked the problem with previous research findings to show the existing gap. For
instance, they acknowledge the fact that previous research has shown an existence of a link
between temperature variations and air pollution by particulate matter in causing respiratory
morbidities and mortalities. Since most of the respiratory tract infections are associated with
inflammations, nitric oxide has been chosen as a non-invasive agent to access the mechanism of
the association between ambient temperatures and particulate matter in respiratory tract infection
3.
2. Study design
This article has adopted a longitudinal panel research design among a study population of people
suffering from type 2 diabetes mellitus in Shanghai, China. In this case, the authors justify the
reasons of selecting a population of type 2 diabetes mellitus patients. In this case, they have
argued that previous studies have indicated that these patients are highly vulnerable to the stimuli
of ambient temperatures because they are in a state of high inflammation. The use of this study

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design fits to answer the research question because it involves making repeated observations on
the same variables, either for a short or long period of time 4. Moreover, bearing in mind that this
study involves the analysis of the effects of exposure of the type 2 diabetes mellitus patients to
ambient temperatures and particulate matters, the actual relationship between exposure and
effects must be presented. The longitudinal study design is most commonly used to test the
cause-effect relationship between different variables. In this case, repeated measures of the
association between ambient temperatures and particulate matter was followed up among the
study participants throughout the study period. Moreover, this design allows the collection of
both qualitative and quantitative data to allow for proper observation on exposure and outcomes
relationship 5. However, this method is associated with drawbacks that would affect the
completion of the research due to increased financial costs of this design requires. There could
also be possibilities of interruptions during the follow-up of the study subjects leading to loss of
follow-up across time.
3. Selection of participants
This study recruited 35 type 2 diabetes mellitus people from the urban communities in Shanghai
China, among a population of 86,000 people. However, this study sample does not look quite
representative of the population. This is because from a sample of 35 people, it would not be
sensible enough to make a general conclusion about 86,000 people. Moreover, the authors have
not presented the method used for the sample selection. It would be better if the selection method
was indicated, alongside the equation for estimation of the sample size so that readers can
understand how a sample of 35 type 2 diabetes mellitus patients was arrived at, and not any other
figure 1. The inclusion of participants who had doctor-diagnosed type 2 diabetes was to ensure
that only participants who were prone to respiratory tract infections as a result of exposure to

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ambient temperatures and particulate matter which is nitric oxide were recruited in this study.
Moreover, the selection of people who had a permanent residence in the study area was to
facilitate the ease of follow-up and prevent possible loss of follow-up which would in turn affect
the final findings 6. In the selection of participants, the researchers excluded people who were
active smokers, suffering from cardiac and pulmonary infections and alcohol drinkers. This is to
rule out the possible respiratory tract infections and inflammation as a result of any other agents
apart from ambient temperatures and particulate matter 7. This is because the named exclusion
features are also known to cause infections to the respiratory tract.
4.Error
Possible errors in this study could be during sampling whereby the sample size selected was so
small as compared to the overall population of the study area. Therefore, this sample size might
not be a representative of the concerned population 8. Selection error could also have occurred,
whereby the issues of gender and age differences have not been highlighted.
5.Bias and Confounding
The effect of confounding of variables is quite clear, by considering the two variables, ambient
temperatures and particulate matter (nitric oxide). While low temperatures increase, the chances
of bacterial and viral infection in the respiratory tract, the nitric oxide also causes inflammation
of the respiratory tract. Therefore, there could be a possibility that the observed association
between the two variables and inflammation on the respiratory tract could be due, totally or in
part to these factors. Therefore, the effects of the confounding variables cause bias when
estimating the impact of the exposures 9. This could for example indicate that there is a
significant difference in the population, when in real sense no difference actually exists. Bias in
this article could be due to loss of follow-up or the observer bias.

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6. Hierarchy of evidence
This research can be classified as type two level of evidence study, since the randomized control
trials fall in level one. This is because this was a longitudinal study involving follow-ups and
repeated observations 10.
7. Chance
It could also be possible that the respiratory tract infections or inflammation which was observed
was not due to the exposure variables but chance 11. This is because, the viral infections could
cause the inflammation due to the weakened immune system of type 2 diabetes mellitus patients
and not an interplay between ambient temperatures and particulate matter. In this case, probably
the use of healthy participants could rule out the issues of chance, in the obtained results.
8. Ethical considerations
This study was approved by the institutional review board at the school health in Fudan
university 1. Application of ethical clearance is usually done before the research begins, which is
the case that happened as outlined in this article 12. Before being granted ethical clearance, a
research must demonstrate through detailed application, that the research will adhere to all
ethical principles 13. Moreover, the study participants were asked to provide a written informed
consent during the enrollment process. Seeking of informed consent was justified because in any
research, more so those involving the use of human subjects, it enables the participants to choose
on whether to participate or not 14. Consent also discloses the details of the research and the
procedures to be used to avoid causing danger to them.
9. Clinical and statistical significance

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The statistical analysis involved the establishment of a link between exposure of the subject to
nitric oxide, and the exact time when the test was performed. In this case, the mixed methods
model was applied alongside the lag nonlinear model for short-term association between ambient
temperature and the particulate matter exposure. The use of mixed methods in this case allowed
the researchers to enable each and every study participant to serve as their own control for the
adjustment of variations especially in longitudinal studies involving repeated measurements from
the same subject during follow-ups. However, the use of the mixed effects model in research
could suffer a number of drawbacks like the production of estimates which have high sample-
sample variations that affects the final results. While the authors have provided various concepts
in statistical analysis, they have also mentioned that the R software version 3.2.0, was used for
data analysis, though no explanation is given for the choice of specifically this analysis tool. The
choice of the relevant data analysis software is very important because it ensures that all
variables are accurately analyzed and the data outputs obtained are sufficient to answer the initial
research question.
Moreover, the article describes that the significance level was considered as p<0.05. The results
for the ambient temperatures were presented in form of relative risk with respect to the nitric
oxide by comparing with reference ranges. Additionally, the results for the particulate matter was
presented in the form of percentages in the increase of nitric oxide based on their increasing
concentrations. Therefore, the statistical analysis is clearly presented and this makes it easy for
the readers to follow up the results manipulations with relative ease. The clinical significance is
clearly illustrated in the results and discussion section of the article. This research reported that
there were significant associations between the short term exposure to ambient low temperature
conditions and the particulate matter of nitric oxide among patients suffering from type 2

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diabetes mellitus in Shanghai China. This is because temperatures provide modifiers in analyzing
the association between nitric oxide and particulate matter. Thus this article provides a clear
epidemiological data and evidence concerning the effects of ambient low temperatures and
inflammation to the respiratory tract. The clinical aspect of this is that the airway system is a
body system which is affected by the stimulus from the physical environment. While previous
epidemiological studies have indicated that the ambient temperatures and particulate matter
causes mortalities and morbidities involving the airway system, the exact mechanisms were not
provided before this research was performed. The link between the low temperatures and nitric
oxide was because the exhaled nitric oxide is produced by a reaction involving the enzyme nitric
oxide synthase 1. This enzyme is activated by internal mediators of the body like cytokines, or by
the external factors like viral and bacterial infections. However, from literature, during cold
weather, that is, low temperatures, there is high prevalence of both viral as well as bacterial
infections, and these could possibly colonize the airways system and cause inflammations which
lead to mortality and morbidity to the patients. This research clearly demonstrates both statistical
as well as clinical significance of the research findings.
10. Publication bias
Publication bias occurs when the researchers choose to present and discuss the results which are
clinically or statistically significant, while withholding other findings 15. For instance, in this
article, the authors have not indicated whether there are some subjects who withdrew from the
research during follow-ups, or whether there are those who died as a result of succumbing to
type 2 diabetes and associated complications. Therefore, it is quite important for the researchers
to appreciate the mechanisms of publication bias and other results-reporting methods so that they
can minimize the negative impacts that could arise during the interpretation of results 16.

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11. Validity- external or internal
The internal validity in this research was achieved because the variables and experimental
procedures were significant enough in answering the research question. The use of patients
suffering from type 2 diabetes mellitus was to ensure that they were easily prone to respiratory
inflammations upon the exposure to ambient temperatures and particulate matter, as compared to
non-diabetic individuals. However, it is not indicated if a variable like age and sex could have
effects on the severity and extent of inflammation. This would have been better explained so as
to determine the age and gender intervals, if any, that could pose a higher risk to this exposure.
At the same time, the manner in which the experiments were conducted followed clear
procedures which can be easily replicated in different studies and hence valid enough. In this
case, nitric oxide was chosen because it has been found to be non-invasive on human beings and
hence suitable for use in the downstream experimental processes.
However, the external validity is not justified because the obtained results cannot be inferred to
the general population in the study area due to the small sample size that was used 17. On the
other hand, the results indicate the mechanism of the exposure and outcome of variables about
these participants, a concept which was lacking in previous epidemiological studies. Therefore,
the outcomes can be generalized, although the sample size of 35 out of the 86,000 people in the
study area still raises some form of doubts about representability of the findings.

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