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\begin{document}

\title{PREVALENCE OF ATOPIC ECZEMA WITH OR WITHOUT WHEEZE IN KOSOVAR
ADOLESCENTS: ROLE OF GENDER, EXERCISE AND PARACETAMOL.}



\author[1]{Luis Garcia-Marcos}%
\author[2]{Luljeta Ahmetaj}%
\author[1]{A. Elena Martínez-Torres}%
\author[3]{Ylli Ahmetaj}%
\author[2]{Valbona Gashi}%
\author[2]{Xhevat Kurhasani}%
\author[2]{Violeta Lokaj-Berisha}%
\author[2]{Besa Gacaferri-Lumezi}%
\author[2]{Mirsije Shahini}%
\author[2]{Valbona Zhjeqi}%
\author[2]{Ahmentaj L}%
\affil[1]{Hospital Clinico Universitario Virgen de la Arrixaca}%
\affil[2]{Universiteti i Prishtines Hasan Prishtina}%
\affil[3]{Kolegji AAB}%


\vspace{-1em}



  
  \date{May 16, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Objectives} To characterise the epidemiology of atopic eczema in
adolescents from Kosovo, an area of very low prevalence of the condition
and to know whether the same factors are associated to eczema with or
without comorbid wheezing symptoms. \textbf{Methods} The cross-sectional
survey Global Asthma Network validated questionnaire was self-completed
by adolescents 13-14 years of age in the school setting from the main
cities of Kosovo: Ferizaj, Gjakova, Gjilan, Peja, Prishtina and Prizren.
Atopic eczema symptoms and diagnosis was put in relation with the
environmental questionnaire which included questions on smoking; pet
ownership; paracetamol use, truck traffic; siblings; time spent using
screens or watching television; and exercise. Additionally, height and
weight were measured at school. \textbf{Results} The prevalence of
eczema symptoms ranged from 2.2\% in Ferizaj to 5.5\% in Gjakova. Severe
symptoms were \textless{}1\% in all cities. Eczema ever ranged from
3.0\% in Ferizaj to 6.4\% in Prizren. Factors significantly associated
to the prevalence of current eczema symptoms in the metanalysis were
male sex (pooled aOR 0.50; 95\%CI 0.37-0.66); exercise (pooled aOR 2.79;
95\%CI 1.89-4.10); and paracetamol intake (pooled 1.86; 95\%CI
1.32-2.64). The corresponding figures for eczema ever were: 0.68 95\%CI
0.44-1.06; 2.07 95\%CI 1.48-2.90; and 1.19 95\%CI 0.88-1.60. The
associations tended to be higher in the subpopulation with eczema and
wheeze comorbidity. \textbf{Conclusions} The prevalence of atopic eczema
is very low in Kosovo and is associated to female sex, exercise, and
paracetamol intake. Those associations are higher when eczema and
wheezing are comorbid conditions.%
\end{abstract}%



\sloppy


\textbf{PREVALENCE OF ATOPIC ECZEMA WITH OR WITHOUT WHEEZE IN KOSOVAR
ADOLESCENTS: ROLE OF GENDER, EXERCISE AND PARACETAMOL.}

Luljeta Ahmetaj\textsuperscript{1*}, A. Elena
Martinez-Torres\textsuperscript{2*}, Ylli Ahmetaj\textsuperscript{3},
Valbona Gashi\textsuperscript{1}, Xhevat Kurhasani\textsuperscript{4},
Violeta Lokaj-Berisha\textsuperscript{1}, Besa
Gacaferri-Lumezi\textsuperscript{1}, Mirsije Shahini\textsuperscript{5},
Valbona Zhjeqi\textsuperscript{1}, Luis
Garc\selectlanguage{ngerman}ía-Marcos\textsuperscript{6}and the Global Asthma Network Phase I
Kosovo Study Group\textsuperscript{7}

\textsuperscript{1}Institute of Physiology \& Immunology, Faculty of
Medicine, University of ''Hasan Prishtina'', Prishtina, Kosovo.

\textsuperscript{2}Paediatric Allergy and Pulmonology Units and Nurse
Research Group, Virgen de la Arrixaca University Children`s Hospital and
IMIB Biomedical Research Institute, Murcia, Spain.

\textsuperscript{3}AAB College. Industriale Prishtinë--Fushë Kosovë.
Prishtina. Kosovo.

\textsuperscript{4}UBT Higher Education Institution. Prishtina. Kosovo.

\textsuperscript{5}Alergji Asthma Ylli'' Polyclinic. Prishtina, Kosovo.

\textsuperscript{6}Paediatric Allergy and Pulmonology Units, Virgen de
la Arrixaca University Children`s Hospital, University of Murcia and
IMIB Biomedical Research Institute, Murcia, Spain.

\textsuperscript{7}Members listed at the end of the paper.

*L Ahmentaj and AE Martinez-Torres should be considered joint first
author.

\textbf{ORCIDs} : L Ahmetaj: 0000-0003-0780-0791; AE Martinez-Torres:
0000-0002-7447-3199; Y Ahmetaj: 0000-0003-1859-8146; V Gashi:
0000-0001-7665-8704; X Kurhasani: 0000-0001-6074-9740; Violeta
Lokaj-Berisha: 0000-0001-9716-0243; B Gacaferri-Lumezi:
0000-0001-5276-167, M Shahini: 0000-0002-5364-7508; V Zhjeqi
0000-0001-7862-9827; Luis Garcia-Marcos: 0000-0002-0925-3851.

\textbf{Running title:} Epidemiology of atopic eczema in Kosovar
adolescents.

\textbf{Acknowledgments:}

We would like to acknowledge all participating children and their
parents, as well as all teacher who facilitated the fieldwork.
Especially to T. Hoxha and H. Hoti, doctors at the Main Family Medicine
Center (Prishtina) who gave all their support to the
study.\emph{Financial Support:} A. Elena Martinez-Torres and L.
Garcia-Marcos partly funded by Instituto de Salud Carlos III, Spain
(grant PI17/0170).

\textbf{Corresponding author:}

Luis Garcia-Marcos

Department of Paediatrics

University of Murcia

Edificio Departamental-LAIB, Avenida Buenavista s/n, 30120 El Palmar,
Murcia, Spain

Phone: +34868888129

Email: \emph{Lgmarcos@um.es}

\textbf{ABSTRACT}

\textbf{Objectives}

To characterise the epidemiology of atopic eczema in adolescents from
Kosovo, an area of very low prevalence of the condition and to know
whether the same factors are associated to eczema with or without
comorbid wheezing symptoms.

\textbf{Methods}

The cross-sectional survey Global Asthma Network validated questionnaire
was self-completed by adolescents 13-14 years of age in the school
setting from the main cities of Kosovo: Ferizaj, Gjakova, Gjilan, Peja,
Prishtina and Prizren. Atopic eczema symptoms and diagnosis was put in
relation with the environmental questionnaire which included questions
on smoking; pet ownership; paracetamol use, truck traffic; siblings;
time spent using screens or watching television; and exercise.
Additionally, height and weight were measured at school.

\textbf{Results}

The prevalence of eczema symptoms ranged from 2.2\% in Ferizaj to 5.5\%
in Gjakova. Severe symptoms were \textless{}1\% in all cities. Eczema
ever ranged from 3.0\% in Ferizaj to 6.4\% in Prizren. Factors
significantly associated to the prevalence of current eczema symptoms in
the metanalysis were male sex (pooled aOR 0.50; 95\%CI 0.37-0.66);
exercise (pooled aOR 2.79; 95\%CI 1.89-4.10); and paracetamol intake
(pooled 1.86; 95\%CI 1.32-2.64). The corresponding figures for eczema
ever were: 0.68 95\%CI 0.44-1.06; 2.07 95\%CI 1.48-2.90; and 1.19 95\%CI
0.88-1.60. The associations tended to be higher in the subpopulation
with eczema and wheeze comorbidity.

\textbf{Conclusions}

The prevalence of atopic eczema is very low in Kosovo and is associated
to female sex, exercise, and paracetamol intake. Those associations are
higher when eczema and wheezing are comorbid conditions.

\textbf{KEY WORDS}

Atopic eczema; Epidemiology; Exercise; Kosovo; Paracetamol.



\textbf{INTRODUCTION}

The prevalence of atopic eczema has increased for the past decades,
although the variability of this trend is high and depends in part on
the region of the world and on the socioeconomic
status\textsuperscript{1}. According to the last report from the Global
Asthma Network (GAN) recently published\textsuperscript{2}, the increase
in adolescents of 13-14 years has been 0.98\% per decade for the las 27
years. In the first GAN survey, carried out between 2015 and 2020, the
prevalence in the group of low and middle-low, and on the upper-middle
income countries, symptoms of current eczema and lifetime eczema were
significantly lower than that of high income
countries\textsuperscript{3}. At the time when the survey was performed,
Kosovo was in the group of upper-middle income
countries\textsuperscript{4}. Additionally, Kosovo, although not having
direct access to the sea, can be considered a Mediterranean country.
This warm and humid area, as compared to others in the world, has shown
relatively low prevalence of atopic eczema\textsuperscript{5} with some
studies pointing at climate, and in particular the number of sunny
hours, as being part of the explanation\textsuperscript{1,6}.

The prevalence of eczema in Kosovo is basically unknown although there
has been some epidemiological data in the Balkan area previously. The
International Study of Asthma and Allergies in Childhood (ISAAC) phase
III (the methodology of which has been used by GAN) reported data from
Albania in the age groups of 6-7 and 13-14 years, which was one of the
world lowest for current symptoms of eczema\textsuperscript{5}. Both in
this ISAAC report and in the more detailed one by Zivkovi\selectlanguage{polish}ć \selectlanguage{english}et
al.\textsuperscript{7} the lowest prevalence of current eczema symptoms
in Serbia and Montenegro was found to be in Novi Sad, (north of Serbia).
However, neither of the two reports, nor previous ones in the
Balkans\textsuperscript{8,9}, included the study of risk or protective
factors for eczema at the individual or centre level. To the best of our
knowledge, only one study in Croatia has reported epidemiological
factors associated to eczema in the Balkan area in
adolescents\textsuperscript{10}. Another one focused on the association
of traffic pollution with allergic diseases\textsuperscript{11}.

Thus, the study of the epidemiology, including potential risk or
protective factors, of eczema in adolescents in the main cities of a
country such as Kosovo could add important information on the subject:
it would show the current size of the problem in an area which has
previously presented low prevalence of the condition; may add
information about the epidemiological factors in a low prevalence region
in order to facilitate comparison with areas of higher prevalence; could
allow for comparisons between centres in the same low-prevalence area;
and might show paths for prevention.

\textbf{METHODS}

The methods of the GAN study have been already published
elsewhere\textsuperscript{12} and are mainly identical to those of
ISAAC. GAN is cross-sectional study based on written questionnaires
distributed in schools in the participating centres. In Kosovo, the
survey included the age group of 13-14-years; and six centres: Ferizaj,
Gjakova, Gjilan, Peja, Prishtina and Prizren. The fieldwork was carried
out between 2017 and 2018.

\textbf{Questionnaires}

The definitions of indicators of atopic eczema were derived from the
written questionnaires completed by adolescents at school. The original
questionnaire was in English, and translation and back-translation to
Albanese followed a specific methodology common to ISAAC and
GAN\textsuperscript{13}

\textbf{Definitions}

``Current eczema symptoms'' was defined as a positive answer to two
questions: ``Have you had this itchy rash (as defined in a previous
question) at any time in the past 12 months?'' and ``Has this itchy rash
at any time affected any of the following places: the folds of the
elbows, behind the knees, in front of the ankles, under the buttocks, or
around the neck, ears or eyes?''. ``Severe eczema symptoms'' was defined
as symptoms of current eczema being the cause of awakening one or more
times per week in the question: ``In the past 12 months, how often, on
average, have you (has this child) been kept awake at night by this
itchy rash? (Never in the past 12 months, less than one night per week,
one or more nights per week). ``Eczema ever'' was defined as a positive
answer to: ``Have you ever had eczema?''.

``Current wheeze'' was defined by a positive answer to the question
``Have you (has your child) had wheezing or whistling in the chest in
the past 12 months? Current wheeze was used to stratify eczema markers
in some of the statistical analyses.

Additionally, adolescents responded to the environmental questionnaire.
This included questions on smoking; pet ownership; paracetamol use,
truck traffic in the street where adolescents lived; siblings; time
spent using screens or watching television; and exercise. Additionally,
height and weight were measured at school by fieldworkers in a
standardised way according to GAN methods\textsuperscript{12}.Exercise
was assessed by the question ``How many times a week do you engage in
vigorous physical exercise activity long enough to make you breath hard?
(Never or occasionally; once or twice per week; three or more times per
week)''. Paracetamol intake was surveyed by the question: ``In the past
12 months, how often, on average, have you taken paracetamol for fever?
(Never; At least once a year; At least once per month)''. Overweight was
defined as body mass index above 25.

\textbf{Sample size and study power}

As for any GAN centre, all students (selected by grade or by age) of
13-14 years within all schools (Ferizaj, Gjakova, Gjilan, Peja, and
Prizren) or within a random sample of them (Prishtina) were invited to
participate to achieve the minimum required sample size of 1000.
Additional details of the sample size and power are described
elsewhere\textsuperscript{12,14} Participation rates in Kosovo (80.0\%
or more) have been also described in detail
previously\textsuperscript{15}.

\textbf{Statistical analysis}

To calculate participation rates, the denominator was the number of
adolescents and the numerator the number of core questionnaires returned
with at least one data symptom. For prevalence estimations, positive
answers to a specific symptom in the centre was divided by the number of
completed questionnaires. There was no data imputation.

All variables included in the GAN environmental questionnaire were used
as independent variables in logistic regression analyses (uni and
multivariate) in which the three eczema markers (current symptoms,
severe symptoms, and current eczema) were the dependent variables. Those
analyses were performed within each centre. As the number of cases of
severe symptoms was very low, logistic regression analyses were not
performed. Factors which showed significant (p\textless{}0.05) values of
adjusted odds ratios in the multivariate logistic regression analyses in
at least one centre were subsequently meta-analysed (random effects)
including the results of the six centres. A forest plot was built,
including the pooled effect together with the 95\%conficence interval
and prediction interval. Measures of heterogeneity, such as Q and
I\textsuperscript{2} were also calculated.

To test whether the presence of current wheeze modified the associations
between the environmental factors and the eczema markers on the whole
sample of adolescents, a multilevel mixed effects logistic regression
model was performed, including the same variables as in the within
centre logistic regressions; and using the individual as the first level
and the centre at the second. As previously and due to the low number of
cases, no analysis was made for symptoms of severe eczema.

Most statistical calculations were made using Stata SE\selectlanguage{ngerman}® v18 software
package (Stata corp., College Station, TX, USA) except meta-analyses
that were carried out using Comprehensive Meta-Analysis (CMA) V4.0
software package (Biostat, Englewood, NJ, USA).

\textbf{Ethics}

Prior to the beginning of the study, permission was asked and
authorisation issued by the education authorities in each municipality.
Passive informed consent was used. The study was approved by the Ethics'
Committees of both the Ministry of Health and the Ministry of Education
of Kosovo according to the Helsinki declaration (approval No. 21/550).

\textbf{RESULTS}

Demographic and environmental characteristics of the 6 Kosovar centres
have been already described\textsuperscript{15}. Table 1 shows the
prevalence of current eczema symptoms, severe eczema symptoms and eczema
ever overall, and with and without wheeze, together with the respective
95\% confidence intervals. The lowest prevalence of current eczema
symptoms occurred in Ferizaj while the highest was in Gjakova. Eczema
ever was lowest in Ferizaj again and highest in Gjakova. Overall, the
proportion of adolescents with eczema and wheezing symptoms was much
lower than that with only eczema symptoms. The prevalence of severe
eczema symptoms was very low and similar among the centres.

Web tables 1 and 2 include the associations found in the univariate and
multivariate logistic regressions of the different factors with current
eczema symptoms and eczema ever, respectively, per centre. Those factors
that were consistently associated with current eczema symptoms or eczema
ever in most centres were sex, exercise, and paracetamol intake. Forest
plots of those three factors showed a trend that male sex (figure 1) was
associated to lower prevalence of eczema: pooled aOR=0.49; 95\%CI
0.37-0.66, for current eczema; and pooled aOR=0.68; 96\%CI 0.44-1.06,
for eczema ever.

Figure 2 shows that exercise was associated to higher prevalence of
current eczema symptoms and eczema ever, with no apparent dose-effect
relationship. The pooled aOR and 95\%CI for any frequency of exercise
was 2.79 (1.89-4.10) and 2.07 (1.48-2.90) respectively for current
eczema symptoms and eczema ever.

Contrary to exercise, paracetamol intake seemed to have a dose-response
pattern of association, especially for current eczema symptoms. The
pooled aOR and 95\%CI were 1.33 (0.81-2.16) and 2.64 (1.61-4.33) for the
intake of ``at least once a year'' and of ``at least once a month'',
respectively. The corresponding figures for eczema ever were: 1.09
(0.75-1.58) and 1.37 (0.85-2.22) (figure 3).

According to the results of the multilevel analyses, stratification by
wheeze did not change the patterns of associations, although in those
children who suffered from skin plus respiratory symptoms those
associations seemed to be stronger. However, the low number of children
in the eczema and wheeze group was considerably lower than in the group
with eczema without wheeze, making comparisons problematic (table 2).

\textbf{DISCUSSION}

In this cross-sectional epidemiological study on atopic eczema in
Kosovo, within the GAN collaboration, we have found very low prevalence
of any of the three atopic eczema markers as compared with other GAN
centres. In fact, only three centres, two in India (Lucknow, 1.9\% and
Mysuru, 1.4\%) and the one in Sri-Lanka (Anuradhapura, 1.1\%) had lower
prevalence of symptoms of current eczema than Ferizaj (2.2\%); and this
centre had the lowest prevalence of severe eczema symptoms, with only
five cases in the whole population surveyed (\textless{}0.5\%). With
respect to eczema ever, only nine into sixteen Mexican centres and one
Indian (Mysuru) had a prevalence lower than 3.0\%, the one found in
Ferizaj. The centre with the highest prevalence of those markers in
Kosovo is Gjakova with 5.5\%, 0.7\% and 6.8\% respectively for current
eczema symptoms, severe eczema symptoms, and eczema ever. Those figures
are also quite low as compared to the rest of GAN
centres\textsuperscript{3}.

Although there has not been any other previous study on the epidemiology
of atopic eczema in Kosovo, there have been some in the Balkan region.
In the ISAAC phase III survey\textsuperscript{5}, carried out around
2002, Tiranë (Albania) reported the prevalence of eczema markers defined
as in the present study as follows: current eczema symptoms, 2.0\%;
severe eczema symptoms, 0.2\%; and eczema ever, 2.9\%, respectively.
Furthermore, the corresponding figures for Rijeka (Croatia) and Skope
(Republic of Macedonia) were 2.9\%, 0.2\% and 8.5\%; and 2.7\%, 0.3\%
and 3.7\%, respectively. There were also data from five centres in
Serbia and Montenegro, which ranged 2.8\%-8.0\%, 0.5\%-1.3\%, and
8.2-17.9\%, respectively. The report by Zivkovi\selectlanguage{polish}ć \selectlanguage{english}et
al.\textsuperscript{7} on Serbia and Montenegro expands further the data
included in the ISAAC phase III report and showed low prevalence rates
of other eczema markers.

Apart from offering the first epidemiological data on atopic eczema in
Kosovo it is also interesting to study epidemiological factors which
might be associated to this condition in a geographical area with very
low prevalence where, to the best of our knowledge, those factors have
not been yet studied among adolescents. Of those studied factors in the
meta-analyses of the six centres, male sex is independently associated
to both a significant lower prevalence of current eczema symptoms and of
eczema ever (if Prizren is excluded in the latter case) (figure 1). The
prevalence of severe eczema symptoms is too low to allow any
multivariate statistics. The influence of sex in atopic eczema has been
previously studied in adolescents in the Balkan area: Stipic-Markovic et
al. \textsuperscript{9} found no association between eczema markers and
sex in Zagreb among adolescents included in the ISAAC phase III survey.
However, other studies have found that different eczema markers are
significantly more prevalent in female sex in this age group, like that
by Mercer et al. carried out in Cape Town (South
Africa)\textsuperscript{16}. In the EPI-CARE study, a recent
international cross-sectional study in children (6 months to
\textless{}12 years old) and adolescents (12 to \textless{}18 years old)
using ISAAC methods and defining atopic dermatitis with the same
criteria as in the present study found that prevalence differences by
sex, in one or the other direction, existed in some countries but not in
others\textsuperscript{17}. However, the authors did not report those
differences separately in the two age groups studied. In the BAMSE
study, a longitudinal population-based cohort study, carried out in
Stockholm, the follow-up visit at age 11-14 years did show a
significantly higher prevalence among females when using an eczema
questionnaire specifically designed for the study\textsuperscript{18}.
The same was found in a large international cross-sectional study among
adults 18--65 years old\textsuperscript{19}, and previously in a Swedish
study on individuals 17-75 years of age which used the
GA\textsuperscript{2}LEN questionnaire to assess eczema
symptoms\textsuperscript{20}. These findings are shared by other
studies\textsuperscript{21,22}. A recent BAMSE report after the visit at
24 years of age of the individuals in the cohort, further extends the
finding of male sex is associated to lower prevalence of eczema
markers\textsuperscript{23}. Sex hormones seem to play a role in this
difference after puberty\textsuperscript{24}.Current eczema symptoms and
eczema ever were also associated to exercise in an apparently not
dose-response fashion. Making regular exercise was significantly
associated with the increase of prevalence of both atopic eczema markers
overall, although this was not the case in some of the centres (figure
2).

As found in the present study, exercise has been associated to eczema
previously, although the information is quite limited. In a systematic
review and metanalysis by Kim et al. \textsuperscript{25} in 2016 only
seven manuscripts were included after searching all relevant literature
databases since their existence. Three studies found some association
between exercise an eczema; three showed an inverse relationship and one
did not find any association. Only five of them had enough data to be
included in metanalysis which yield non-significant summary effects, but
interestingly, the only study in adolescents\textsuperscript{26} showed
a significant positive association. Both the two other studies (not
included in the metanalysis) which found positive associations were also
performed in in children or adolescents\textsuperscript{27,28}. Only one
of the studies showing no association was in adolescents. It should be
noted that this one only included 481 individuals\textsuperscript{29}.
All those studies in adolescents and children used the ISAAC
methodology, which requires a sample size of 3000. More recent studies
offer additional information. For instance, Jago et
al.\textsuperscript{30}, using accelerometers in a ALSPAC population of
6473 adolescents, concluded that the number of minutes of vigorous
exercise is not related either to asthma or to eczema, but it is
inversely associated to obesity. The nature of the ISAAC studies
(cross-sectional) vs. de ALSPAC (longitudinal) and the different ways of
measuring exercise (simple questionnaire vs. accelerometer) can explain
the discrepancy. However, it cannot be ruled out that low to moderate
exercise is associated to higher prevalence of eczema, while moderate to
vigorous is not. It well might be that low intensity exercise with skin
exposure to environment and climate aggression and sweat could
facilitate mild eczema flares in not highly predisposed individuals;
and, in contrast, those highly predisposed avoid vigorous exercise to
escape from severe flares. In fact, higher disease severity is
associated with decreased levels of physical activity secondary to itch,
in adults, has been previously shown\textsuperscript{31}. The curve of
the association between the amount of exercise and the severity of
eczema (and thus, awareness in self-reported surveys) might have an
inverted U shape.

On the other hand, Honjo et al. \textsuperscript{32} found a positive
independent association of exercise induced wheeze with eczema in a
group of 12,405 asthmatic children 6 to 18 years of age following ISAAC
definitions. This is probably in keeping with our findings that the
association of exercise with eczema is higher in those adolescents who
also reported current wheeze (table 2). We cannot say whether the
proportion of atopy was higher in the individuals who wheeze than in
those who did not wheeze, but this possibility cannot also be ruled out.

The third variable that was consistently associated to eczema markers
was taking paracetamol, both at least once last year and at least once
last month (figure 3). This was more consistent for current eczema
symptoms than for eczema ever and was probably driven by those
individuals who have both eczema and wheeze (table 2). There have been
several reports linking the use of paracetamol with eczema, even showing
that this association is higher when several allergic diseases
coexist\textsuperscript{33-36}. Thus, it cannot be said whether the
association between paracetamol and eczema might be driven by asthma
and/or rhino-conjunctivitis and/or allergy. The present study shows that
the association with frequent use (at least one last month) holds even
among those adolescents without current wheeze, but only for current
symptoms of the condition. The effect of early paracetamol intake on
eczema in children 6-7 years of age with neither asthma nor
rhino-conjunctivitis symptoms, has been previously
shown\textsuperscript{37}. This probably indicates that the drug impairs
the antioxidant system which is crucial to maintain skin integrity after
aggression\textsuperscript{38}.

The present study has a main weakness which is its cross-sectional
nature, precluding to obtain any causal relationship. On the other hand,
the study was conducted using validated methods, on a quite large sample
with high participation rate, which is representative of the whole
country of Kosovo. It has the additional interest of being an area with
quite low prevalence of atopic eczema.

In summary, this study shows that, in an area of low prevalence of
atopic eczema, both sex, exercise and paracetamol intake are associated
to the number of eczema cases, also in those adolescents without current
asthma symptoms. Male sex is associated to lower prevalence while mild
to moderate exercise and frequent use of paracetamol are associated to
higher prevalence of the condition.

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Busquets-Monge RM, Suarez-Varela MM, et al. Early exposure to
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\textbf{Conflict of interests}

The authors declare no conflict of interest.

\textbf{Data sharing}

The study protocol including a recommended informed consent form and
statistical analysis plan are in the public domain. The GAN Phase I
data, including de-identified individual participant data, will be made
available on the Global Asthma Network website
http://www.globalasthmanetwork.org/ within 12 months of all GAN Phase I
analyses being published. Access will require a formal request, a
written proposal and a signed data access agreement.

\textbf{Global Asthma Network Phase I Kosovo Study Group:}

LN Ahmetaj*, R Baftiu, Y Ahmetaj, M Shahini, G Parduzi, D Ahmetaj, A
Kafexholli, D Musliu, A Deva, A Rabushaj, E Blyta, A Breznica, I Jakupi,
F Spahiu, University of Prishtina ''Hasan Prishtina'', Medical Faculty,
Kosovo (Prishtina); I Bucaliu-Ismajli, The Principal Center of Family
Care (Ferizaj); L Pajaziti, University Hospital Clinic, Clinic of
Dermatology, Prishtina, Kosovo (Gjakova); L Hana-Lleshi, General
Hospital ''Isa Grezda'' Gjakova, Kosovo (Gjakova Adults); V Ghashi,
Regional Hospital, ''Sami Haxhibeqiri'' Mitrovica, Kosovo (Gjilan); X
Kurhasani, UBT College, Kosovo (Peja); B Gacaferri-Lumezi, University of
Prishtina ''Hasan Prishtina'', Medical Faculty, Kosovo (Peja 6-7); V
Zhjeqi, University of Prishtina (Prizren); V Lokaj-Berisha, University
of Prishtina (Prizren Adults).

* Kosovo principal investigator.

Table 1. Prevalence of current eczema symptoms, severe eczema symptoms
and eczema ever, overall and with and without wheezing in six Kosovar
cities (\% and 95\% Confidence Interval)\selectlanguage{english}\textsuperscript{+}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{FERIZAJ} N=890\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{GJAKOVA} N=676\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{GJILAN} N=1200\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{PEJA} N=1433\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{PRISHTINA} N=1056\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{PRIZREN} N=1427\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Current eczema symptoms\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.2 (1.5-3.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.5 (4.0-7.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.1 (3.1-5.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.0 (4.0-6.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.3 (4.1-6.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.6 (3.6-5.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Without wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.0 (1.3-3.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.3 (3.9-7.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.2 (2.3-4.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.6 (2.8-4.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.1 (3.1-5.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.7 (2.8-4.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
With wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.2 (0.06-0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.2 (0.02-1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.9 (0.5-1.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.5 (1.0-2.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.3 (0.7-2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.0 (0.6-1.7)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Severe eczema symptoms\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.7 (0.3-1.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.6 (0.3-1.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.6 (0.3-1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.5 (0.2-1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.6 (0.3-1.1)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Without wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.6 (0.2-1.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.5 (0.2-1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.4 (0.2-0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.4 (0.1-1.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.4 (0.2-0.9)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
With wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.1 (0.02-1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.08 (0.01-0.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.1 (0.04-0.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.1 (0.01-0.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.1 (0.04-0.6)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Eczema ever\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.0 (2.1-4.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.8 (5.1-9.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2 (3.2-5.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.7 (4.6-7.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.0 (3.0-5.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.4 (5.3-7.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Without wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.4 (1.6-3.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.0 (4.4-8.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.4 (2.5-4.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.7 (3.7-5.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.7 (2.7-5.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.1 (4.1-6.4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
With wheeze\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.7 (0.3-1.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.9 (0.4-2.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.8 (0.4-1.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.1 (0.7-1.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.3 (0.1-0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.5 (0.1-2.3)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}See text for definitions.

\textsuperscript{++}No cases.

Table 2. Associations (adjusted\textsuperscript{+} odds ratios) and
their 95\%CI (in parenthesis) between sex, exercise, and paracetamol
intake with current eczema symptoms (upper panel) and eczema ever (lower
panel) in six Kosovar cities in the mixed effects multilevel logistic
regression analyses.

\textbf{Current eczema symptoms}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Overall}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{With wheeze}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Without wheeze}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Male sex\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.52 (0.39-0.68)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.52 (0.39-0.71)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.50 (0.27-0.92)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Exercise\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Never or occasionally\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Once or twice per week\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.59 (1.97-13.41)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.22 (1.65-3.00)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
6.10 (2.90-12.4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Three or more times per week\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
3.11 (2.14-4.53)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.30 (1.47-3.57)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
10.0 (4.47-22.5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Paracetamol in the last 12 months\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
At least once\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.50 (0.98-2.30)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.34 (0.85-2.10)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
3.70 (0.84-16.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
At least once per month\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.75 (1.81-4.17)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.39 (1.54-3.72)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
7.16 (1.69-30.5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Eczema ever}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Eczema ever}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Eczema ever}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Eczema ever}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Ever}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{With wheeze}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Without wheeze}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Male sex\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.72 (0.56-0.92)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.69 (0.52-0.90)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.88 (0.50-1.56)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Exercise\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Never or occasionally\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Once or twice per week\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.68 (1.29-2.19)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.56 (1.17-2.09)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.31 (1.27-4.19)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Three or more times per week\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.04 (1.40-2.97)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.78 (1.16-2.74)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
3.32 (1.57-7.00)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Paracetamol last 12 months\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
At least once\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.16 (0.83-1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.14 (0.80-1.64)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.29 (0.53-3.10)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
At least once per month\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.44 (1.02-2.03)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.29 (0.88-1.88)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
2.34 (1.00-5.47)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}Adjusted for all the variables in the table, and for
age, screen and television time, siblings, truck frequency, cat and dog
ownership, tobacco smoking, vaping and overweight.

\textbf{Figure legends}

Figure 1. Forest plot of the random meta-analysis of the association of
sex with current eczema symptoms (flexural itchy rash -upper panel) and
eczema ever (lower panel). Q=5.03, p=0.412; I\textsuperscript{2}=0.68\%,
and Q=13.7, p=0.018; I\textsuperscript{2}=63.5\%, respectively.

Figure 2. Forest plot of the random meta-analysis of the association of
exercise with current eczema symptoms (flexural itchy rash -upper panel)
and eczema ever (lower panel). Q=24.34, p=0.011 (overall);
I\textsuperscript{2}=54.81\% (overall); and Q=24,31, p=0.011;
I2=54.75\%, respectively.

Figure 3. Forest plot of the random meta-analysis of the association of
paracetamol intake with current eczema symptoms (flexural itchy rash
-upper panel) and eczema ever (lower panel). Q=16.31, p=0.130 (overall);
I\textsuperscript{2}=32.57\% (overall); and Q=12.26, p=0.344;
I\textsuperscript{2}=10.29\%, respectively.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

