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\begin{document}

\title{Assessing the impact of a school program of early detection of asthma}



\author[1]{Luciano Busi}%
\author[1]{Sabrina Fernández}%
\author[2]{Peter Sly}%
\affil[1]{Trelew Hospital}%
\affil[2]{University of Queensland}%


\vspace{-1em}



  
  \date{May 07, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Wheeze-associated disorders are common in childhood,
associated with considerable morbidity, if not detected and treated.
Under diagnosis of asthma remains a problem, especially in
resource-limited settings. Methods: We used a validated school-based
screening questionnaire to detect children likely to have asthma.
Children with positive screening were referred to the Pulmonology
Department for clinical review and lung function testing. We compared
asthma-like symptoms, activity limitation, school absence and health
service utilization before and after in those diagnosed with, and
treated for asthma. Results: 6400 children, from a potential population
of 70,000 were screened between 2010 and 2016, with 900 (14.1\%)
screening positive. Lung function data were available from 578 (64.2\%)
children (5.7 to 6.5 years old). Asthma was confirmed in 549 children;
438 were treated with short acting bronchodilator alone and 111 with
inhaled corticosteroids. Asthma control improved in 58\% of children,
with fewer daytime {[}mean 4.7 (SD1.9), vs 11.1 (0.6) days per week,
p\textless{}0.001{]} and nocturnal {[}4.3 (1.1) vs 0.89 (0.5) days per
month, p\textless{}0.001{]} symptoms. Activity improved and fewer school
days were lost due to asthma {[}12.8 (3.0) vs 1.9 (0.9) days in past 3
months, p\textless{}0.001{]} in over 50\% of children. Emergency
department visits were reduced {[}1.8 (0.7) vs 0.3 (0.2) visits in past
3 months, p\textless{}0.001{]} in over 80\% of children. Conclusions:
Asthma under diagnosis remains a problem in Argentina. Our school-based
assessment is an effective tool for detecting children with undiagnosed
asthma. Instituting effective asthma treatment in these children reduces
symptoms and improves control.%
\end{abstract}%



\sloppy


Assessing the impact of a school program of early detection of asthma

Luciano E Busi MD\textsuperscript{1,2}, Sabrina G Fern\selectlanguage{ngerman}ández
MD\textsuperscript{2,3}, Peter D Sly MD, DSc\textsuperscript{4}

\textsuperscript{1}Pulmonology Committee of the Argentinean Pediatric
Society, Argentina.

\textsuperscript{2}Trelew Hospital, Argentina.

\textsuperscript{3}Puerto Madryn Hospital, Argentina.

\textsuperscript{4}Children's Health and Environment Program, Child
Health Research Centre, University of Queensland, Brisbane, Australia.

Funding: Trelew Hospital, Argentina.

Address for Correspondence: lucianobusi2@gmail.com

Keywords: disease screening, questionnaire, Argentina, children

Running title: School-based asthma screening

\textbf{Summary/Abstract (249/250 words)}

Background: Wheeze-associated disorders are common in childhood,
associated with considerable morbidity, if not detected and treated.
Under diagnosis of asthma remains a problem, especially in
resource-limited settings.

Methods: We used a validated school-based screening questionnaire to
detect children likely to have asthma. Children with positive screening
were referred to the Pulmonology Department for clinical review and lung
function testing. We compared asthma-like symptoms, activity limitation,
school absence and health service utilization before and after in those
diagnosed with, and treated for asthma.

Results: 6400 children, from a potential population of 70,000 were
screened between 2010 and 2016, with 900 (14.1\%) screening positive.
Lung function data were available from 578 (64.2\%) children (5.7 to 6.5
years old). Asthma was confirmed in 549 children; 438 were treated with
short acting bronchodilator alone and 111 with inhaled corticosteroids.
Asthma control improved in 58\% of children, with fewer daytime {[}mean
4.7 (SD1.9), vs 11.1 (0.6) days per week, p\textless{}0.001{]} and
nocturnal {[}4.3 (1.1) vs 0.89 (0.5) days per month,
p\textless{}0.001{]} symptoms. Activity improved and fewer school days
were lost due to asthma {[}12.8 (3.0) vs 1.9 (0.9) days in past 3
months, p\textless{}0.001{]} in over 50\% of children. Emergency
department visits were reduced {[}1.8 (0.7) vs 0.3 (0.2) visits in past
3 months, p\textless{}0.001{]} in over 80\% of children.

Conclusions: Asthma under diagnosis remains a problem in Argentina. Our
school-based assessment is an effective tool for detecting children with
undiagnosed asthma. Instituting effective asthma treatment in these
children reduces symptoms and improves control.

\subsection*{Introduction}

{\label{introduction}}

Wheezing disorders in children, frequently called asthma (1), are common
causes of morbidity and mortality in children. The world has seen an
epidemic increase in asthma in recent decades, starting in high income
countries and proceeding to middle and low income countries (2). Seminal
studies conducted as part of the International Study of Asthma and
Allergies in Children (ISAAC) have documented changes in prevalence in
various part of the world between the late 1990s and mid 2000s (3-5).
The prevalence reported for Latin American countries showed considerable
variability (3-5), with that reported for Argentina being around 10 to
20\%.

Despite improved diagnosis and management in many parts of the world,
under diagnosis of asthma is still a major problem, especially in
impoverished communities and in low and middle income countries (LMICs)
(2, 6-8). This is especially true for young children, despite specific
guidelines produced for the under five year olds (9). Under diagnosis is
frequently associated with inappropriate management and increased
morbidity including school absence and disturbance of family work
practices with consequent economic consequences for the family and
society (6, 7). The need for timely and accurate diagnosis in young
children is recognized (7), is considered as a research priority (10),
and forms part of a recently published Children's Asthma Charter that
sets out the rights and expectations of children with asthma (11).
Appropriate diagnosis and management leads to improved outcomes for
children and their families (7).

Wheeze and asthma-like symptoms are common in preschool-aged children
and around 80\% of those with persistent asthma have symptoms
originating in early life (12). However, only approximately 30\% of
preschoolers with recurrent wheeze will go on to have childhood asthma
(12). The consequence of not having an accurate diagnosis is often
inappropriate treatment with antibiotics or with inhaled corticosteroids
plus long-acting beta agonists (9, 13, 14). Appropriate diagnosis at
early school age with appropriate management according to guidelines is
likely to improve outcome in individual children and reduce the need for
health care utilization (7, 14, 15).

Very few studies worldwide (and none in Latin America) have evaluated
the impact of the programs designed to screen for asthma in children in
the early school years. We developed and validated programs for early
detection of under-diagnosed or under-treated asthmatic children
attending the first grade of school (16) or kindergarten (17). The aim
of the present study was to determine the impact of early diagnosis and
treatment of asthma in school-aged children in Chubut, Argentina.

\subsection*{Material and methods}

{\label{material-and-methods}}

The program, known locally as PDPACh (Programa de Detección Precoz de
Asma en escuelas de la Provincia de Chubut {[}Early School
Case-Detection Asthma Program in Chubut province{]}), aids early
detection of asthma in first grade school children in Chubut province,
Argentina (16). Parents completed a previously validated questionnaire
(Table 1) and children with a positive result were referred to the
Pulmonology Department, Trelew Hospital, for assessment. The study
protocol was approved by the Bioethics Committee and Committee for
Teaching and Research, Trelew Hospital and Parents gave written consent
for their child's participation.

Data were collected from children referred for asthma assessment before
and after parents completed PDPACh. We compared data from the 3 months
prior to receiving the questionnaire with the 3 months after in terms
of: 1) number of days per week with daytime symptoms; 2) number of days
per month with nocturnal symptoms; 3) number of days per week with
restriction of usual activity; 4) number of lost school days due to
asthma in the 3 months period; 5) number of visits to an emergency
service due to asthma symptoms; 6) asthma control using the Asthma
Control Test and classified according to the Global Initiative for
Asthma (GINA) criteria; and 7) lung function.

Lung function

Spirometry was performed following ATS guidelines modified for children
(18) by the same technician on all occasions. Forced expiratory volumes
and flows were reported, together with the response to bronchodilator
for appropriate outcome variables. Lung function outcome variables were
reported as Z-scores using the GLI Caucasian equations (19), as
validated for Argentinian children (20).

Statistical analysis

Comparisons before and after assessment were made using paired-t tests,
chi-square and ANOVA using SPSS version 23.0. Statistical significance
was accepted at the 5\% level.

Table 1. Parent Questionnaire (PQ) (translated). The original Spanish
version is available in Busi et al. (16)\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Does your child ..} & \textbf{Never} & \textbf{Sometimes} &
\textbf{A lot} & \textbf{Don't know}\tabularnewline
\midrule
\endhead
Develop coughs that won't go away? & & & &\tabularnewline
Wake up at night because of difficulty breathing? & & & &\tabularnewline
Have a hard time taking a Deep breath? & & & &\tabularnewline
Make noisy or wheezy sounds when breathing (awake)? & & &
&\tabularnewline
Complain about a chest that feels tight or hurts after running, playing
hard or doing sports? & & & &\tabularnewline
Wake up at night coughing? & & & &\tabularnewline
Cough after running, climbing stairs or playing sports? & & &
&\tabularnewline
Miss days of school (absent from school) because of breathing problems?
& & & &\tabularnewline
& \textbf{No} & \textbf{No} & \textbf{Yes} & \textbf{Don't
know}\tabularnewline
Has a doctor or nurse told you that your child has asthma, reactive
airways disease or wheezy bronchitis? & & & &\tabularnewline
Has your child stayed in the hospital overnight for asthma or for
trouble breathing? & & & &\tabularnewline
Does your child take medicine or use an inhaler for asthma? & & &
&\tabularnewline
\bottomrule
\end{longtable}

\subsection*{Results}

{\label{results}}

During the period between 2010 and 2016 the questionnaire was completed
by parents of approximately 6400 children from a total potential
population of approximately 70,000 children (9.1\%). For the present
study, we attempted to contact 900 families of children with a positive
screening questionnaire (14.1\%). Study data were retrieved for 578
(64.2\%) children (5.7 to 6.5 years old) referred for asthma assessment
from whom lung function data were available. Asthma was confirmed in 549
children, 438 were treated with short acting bronchodilator alone and
111 with inhaled corticosteroids.

On grouped data, marked improvements were seen in all of the clinical
variables assessed, in asthma control and in lung function (Table 2).
Asthma control was improved in 58\% of children, with fewer daytime and
nocturnal symptoms and improved activity and fewer days off school due
to asthma in more than 50\% of children. Emergency department visits
were reduced in more than 80\% of children.

\textbf{Table 2:} Asthma-like symptoms, activity limitation, health
service utilization and asthma control in the 3 months before and after
asthma diagnosis and treatment.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Variable & Pre-assessment & Post-assessment & p\tabularnewline
\midrule
\endhead
Days per week with daytime symptoms. Mean (SD) & 4.7 (1.9) & 1.1 (0.6) &
0.001\tabularnewline
Days per month with nocturnal symptoms. Mean (SD) & 4.3 (1.1) & 0.8
(0.5) & 0.001\tabularnewline
Days per week of activity limitation. Mean (SD) & 3.8 (1.5) & 0.7 (0.3)
& 0.001\tabularnewline
Days off school due to asthma past 3 months. Mean (SD) & 12.8 (3.0) &
1.9 (0.9) & 0.001\tabularnewline
ED visits for asthma past 3 months. Mean (SD) & 1.8 (0.7) & 0.3 (0.2) &
0.001\tabularnewline
\vtop{\hbox{\strut Asthma control: Well controlled}\hbox{\strut Partly
controlled asthma}\hbox{\strut Uncontrolled asthma}} & 18\% 68\% 14\% &
76\% 21\% 3\% & 0.001 0.007 0.010\tabularnewline
Lung function* FVC (z-score), mean (SD) FEV\textsubscript{1} (z-score),
mean (SD) FEV\textsubscript{0.75} (z-score), mean (SD)
FEF\textsubscript{25-75} (z-score), mean (SD) FEV\textsubscript{0.75}
(\%) change with salbutamol (SD) & -0.34 (0.76) -0.85 (0.91) -0.79
(0.83) -0.98 (0.78) 12.4 (11.7) & -0.27 (0.71) -0.21 (0.89) -0.15 (0.81)
-0.08 (0.69) 5.4 (5.0) & 0.061 0.021 0.019 0.025 0.003\tabularnewline
\bottomrule
\end{longtable}

*z-scores according to Caucasian GLI equations.

\textbf{Discussion}

The results from the present study confirm previous reports on the
benefits of achieving an appropriate asthma diagnosis in young children.
Those in whom asthma was diagnosed and treated appropriately following a
positive screening questionnaire (16) showed improvements in lung
function, reduction in symptoms, reduced health care service utilization
and improved asthma control. On an individual basis, 318 (58\%) children
had improved asthma control, 289 (50\%) children missed fewer day of
school and 439 (80\%) children had fewer visits to the emergency
department for asthma-like symptoms.

Under diagnosis of asthma remains a major problem, especially in
resource limited situations. The recently published ``Worldwide Charter
for Children with Asthma'' (11) recognizes this issue as a major problem
for children globally. The first item listed under the heading ``Rights
of Children with Asthma'' is `I deserve a timely and accurate diagnosis
of asthma within the primary care/community setting'. (11). As outlined
by a recent Concise Clinical Review (21) ``Under diagnosis can occur
either because the patient has not communicated his/her symptoms to a
physician, because the physician has not assigned a diagnosis to explain
the patient's symptoms, or because the physician has attributed the
patient's respiratory symptoms to a condition other than asthma.'' In
the LMIC setting one might add ``where the family does not have access
to appropriate health care'' and in the pediatric setting, the failure
to recognize asthma-like symptoms in young children further compounds
the problem (9). The results from the present study show that under
diagnosis can be a major problem in children in the early school years.
Fourteen percent (900/6400) of children returned a positive screening
questionnaire. We were able to contact and obtain data from 578 children
and 95\% (549/578) of these were diagnosed with and treated for asthma.
Even if those families whose children had a very positive outcome from
the screening questionnaire were more likely to respond to our contact
attempts, this is still a remarkable outcome. Even if the 322 children
whose families did not respond did not benefit, this still leaves 61\%
(549/900) children with major benefits from appropriate asthma diagnosis
and treatment following the positive screening questionnaire.
Extrapolating further, assuming the children of the 6,400 families
completing the questionnaire were representative of the potential total
70,000 population, a positive screen rate of 14\% (6,400/70,000) would
see 9,800 children return a positive screening questionnaire, with
between 5978 ( at a rate of 61\%) and 9310 (at a rate of 95\%) under
diagnosed and under treated asthmatic children.

In summary, under diagnose and under treatment of asthma in the early
school years remains a major problem in Argentina. The program of early
detection of asthma with questionnaires in the province of Chubut,
Argentina is an effective instrument to identify under diagnosed or
undertreated asthmatic children and reduced morbidity, improve lung
function and school attendance and reduce health care service
utilization in young children.

\textbf{References}

1. Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, et
al. After asthma: redefining airways diseases. Lancet. 2018;391:350-400.

2. Dharmage SC, Perret JL, Custovic A. Epidemiology of Asthma in
Children and Adults. Frontiers in Pediatrics. 2019;7:246.

3. Worldwide variation in prevalence of symptoms of asthma, allergic
rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study
of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet.
1998;351:1225-32.

4. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK,
et al. Worldwide time trends in the prevalence of symptoms of asthma,
allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One
and Three repeat multicountry cross-sectional surveys. Lancet.
2006;368:733-43.

5. Sole D, Mallol J, Camelo-Nunes IC, Wandalsen GF. Prevalence of
rhinitis-related symptoms in Latin American children - results of the
International Study of Asthma and Allergies in Childhood (ISAAC) phase
three. Pediatric Allergy and Immunology. 2010;21(1 Pt 2):e127-36.

6. Cruz AA, Stelmach R, Ponte EV. Asthma prevalence and severity in
low-resource communities. Current opinion in allergy and clinical
immunology. 2017;17(3):188-93.

7. Fischer GB, Sarria EE, Camargos P, Mocelin HT, Soto-Quiroz M, Cruz
AA, et al. Childhood asthma in low and middle-income countries: Where
are we now? Paediatric Respiratory Reviews. 2019;31:52-7.

8. Kjaergaard J, Anastasaki M, Stubbe Ostergaard M, Isaeva E, Akylbekov
A, Nguyen NQ, et al. Diagnosis and treatment of acute respiratory
illness in children under five in primary care in low-, middle-, and
high-income countries: A descriptive FRESH AIR study. PloS one.
2019;14(11):e0221389.

9. Pedersen SE, Hurd SS, Lemanske RF, Becker A, Zar HJ, Sly PD, et al.
Global strategy for the diagnosis and management of asthma in children 5
years and younger. Pediatric Pulmonology. 2010;46:1-17.

10. Mathioudakis AG, Custovic A, Deschildre A, Ducharme FM, Kalayci O,
Murray C, et al. Research Priorities in Pediatric Asthma: Results of a
Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in
Real Life (PeARL) Think Tank. The Journal of Allergy and Clinical
Immunology In Practice. 2020.

11. Szefler SJ, Fitzgerald DA, Adachi Y, Doull IJ, Fischer GB, Fletcher
M, et al. A worldwide charter for all children with asthma. Pediatric
Pulmonology. 2020;55(5):1282-92.

12. Castro-Rodriguez JA. The necessity of having asthma predictive
scores in children. Journal of Allergy and Clinical Immunology.
2013;132(6):1311-3.

13. AIHW:, Correll P, Poulos L, Ampon R, Reddel H, Marks G. Respiratory
Medicaton use in Australia. Canberra: AIHW; 2015. Contract No.: Cat. no.
ACM31.

14. Australian Centre for Asthma Monitoring. Asthma in Australian
children: findings from \emph{Growing up in Australia} , the
longitudinal study of Australian children. Canberra: AIHW; 2009.

15. Reddel HK, Bateman ED, Becker A, Boulet LP, Cruz AA, Drazen JM, et
al. A summary of the new GINA strategy: a roadmap to asthma control.
European Respiratory Journal. 2015;46(3):622-39.

16. Busi LE, Sly PD, Restuccia S, Llancam\selectlanguage{ngerman}án L. Validation of a
school-based written questionnaire for asthma case identification in
Argentina. Pediatric Pulmonology. 2012;47(1):1-7.

17. Busi LE, Sly PD, Llancaman L. Validation of a questionnaire for
asthma case identification in pre-schools in Latin America. Respirology.
2015;20(6):912-6.

18. Arets HGM, Brackel HJL, van der Ent CK. Forced expiratory manoeuvres
in children: do they meet ATS and ERS criteria for spirometry? European
Respiratory Journal. 2001;18(4):655.

19. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et
al. Multi-ethnic reference values for spirometry for the 3-95-yr age
range: the global lung function 2012 equations. European Respiratory
Journal. 2012;40(6):1324-43.

20. Busi LE, Sly PD. Validation of the GLI-2012 spirometry reference
equations in Argentinian children. Pediatric pulmonology.
2018;53(2):204-8.

21. Aaron SD, Boulet LP, Reddel HK, Gershon AS. Underdiagnosis and
Overdiagnosis of Asthma. American Journal of Respiratory and Critical
Care Medicine. 2018;198(8):1012-20.

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