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\begin{document}

\title{Pseudomonas aeruginosa in children with cerebral palsy: a prospective
study}



\author[1]{Katrien Romaen}%
\author[2]{Isabelle Van Ussel}%
\author[3]{Carolin Van Rossem}%
\author[1]{Sandra Kenis}%
\author[1]{Berten Ceulemans}%
\author[4]{Kim Van Hoorenbeeck}%
\author[4]{Stijn Verhulst}%
\affil[1]{Universitair Ziekenhuis Antwerpen}%
\affil[2]{AZ Voorkempen}%
\affil[3]{ZNA Koningin Paola Kinderziekenhuis}%
\affil[4]{Universiteit Antwerpen}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\selectlanguage{english}
\begin{abstract}
As we know life expectancy in CP can improve by both preventive
measurements as initiation of early therapy concerning respiratory
morbidity. The prevalence of PA in this prospective study of children
with CP is low, gram-negative bacteria were most commonly found.
Therefore, it is recommended to repeat and expand this study since the
prevalence of respiratory tract infections is again increasing in the
post-covid era.%
\end{abstract}%



\sloppy


\textbf{Pseudomonas aeruginosa in children with cerebral palsy: a
prospective study}

Katrien Romaen, MD\textsuperscript{1*}; Isabelle Van Ussel,
MD\textsuperscript{2*}; Carolin Van Rossem\textsuperscript{3*}; Sandra
Kenis MD\textsuperscript{1}; Berten Ceulemans MD,
PhD\textsuperscript{1}; Kim Van Hoorenbeeck, MD, PhD\textsuperscript{4};
Stijn Verhulst MD, PhD\textsuperscript{4}

\textsuperscript{1} Department of Paediatric Neurology, Antwerp
University Hospital/University of Antwerp, Belgium.

\textsuperscript{2} Department of Paediatrics, AZ Voorkempen, Malle,
Belgium.

\textsuperscript{3} Department of Pediatrics, ZNA Queen Paola Children's
Hospital, Antwerp, Belgium.

\textsuperscript{4} Department of Paediatric Pulmonology, Antwerp
University Hospital and Lab of Experimental Medicine and Pediatrics,
University of Antwerp, Antwerp, Belgium.

* These authors contributed equally

\textbf{Correspondence} : Katrien Romaen, department of Pediatric
Neurology, Antwerp University Hospital. Drie Eikenstraat 655 2650
Edegem, Belgium.

E-mail: Katrien.romaen@uza.be

To the Editor.

Children with cerebral palsy (CP) often present with chronic respiratory
symptoms. This is an import risk factor for increased morbidity and
mortality in children with CP. \emph{Pseudomonas aeruginosa} (PA), is a
known pathogen associated with more severe respiratory disease. Due to
its ability to change its phenotype, an infection with PA is often
chronic and PA is very difficult to eradicate. CP is often accompanied
by multisystem medical concerns like epilepsy, secondary musculoskeletal
problems and impairment in cognition, communication, behavior,
perception, motor control and sensation (1,3,4,5). The degree or
severity of motor disability is classified by the Gross Motor Function
Classification System (GMFCS), a higher score indicates increasing
severity and lower life expectancy (1,5). Patients with CP have a
shorter life expectancy than the general population and the observed
morbidity and mortality is especially linked to respiratory disease
(1,2,4,5). The impact of respiratory morbidity on the quality of life
cannot be underestimated (1,3,5). The reasons for these respiratory
complications are probably multifactorial. Risk factors for hospital
admission include the severity of gross motor disfunction reflected by
GMFCS score, epilepsy, axial hypotonia, limited shoulder movement,
severe kyphoscoliosis, swallowing problems, gastroesophageal reflux
disease (GERD), gastrostomy feeding and absence or impairment of
spontaneous cough (1,4). Other medical conditions also influence
hospitalization rate, quality of life and life expectancy, including
overt or silent aspiration, impaired mucociliary clearance,
kyphoscoliosis, upper or lower airway obstruction and recurrent
infections leading to bronchiectasis. One study showed that the presence
of abnormal bacterial flora (including Pseudomonas and Klebsiella
species) in children with CP who are critically ill occurred twice as
frequent compared to those critically ill without CP (2).

From experience in children with cystic fibrosis, it is known that
chronic colonization of the lower airways with PA is a risk factor for
repeated lung infections, deterioration in lung function and shortened
survival (6).~ It is also known that early therapy will prevent chronic
colonization (6). Preventive actions to eradicate this bacterium and to
improve the respiratory condition of children with CP could therefore be
of interest. The prevalence and role of PA, however, is relatively
unknown in this population. Therefore, we assessed the prevalence of PA
and its association with respiratory disease in a prospective study
including patients, aged 0-18 years, with a diagnosis of CP who attended
either specialised day care centres in Flanders and/or the Antwerp
Reference Centre of Cerebral Palsy in the Antwerp University Hospital.
Exclusion criteria included a known presence of PA defined as a throat
swab with a positive culture for PA and eradication treatment in the
last month before inclusion. Inclusion was done during two periods.
Informed parental consent was obtained. First inclusion was done between
August 2017 to January 2018. To further expand the study, new inclusions
were done from January 2020 to September 2020. Demographic data,
respiratory characteristics and data of comorbidities from patient
records were extracted from the electronic medical records (\emph{Table
1} ). Follow-up of respiratory symptoms was done by the Liverpool
respiratory symptom questionnaire (LRSQ) after 3 months.~~Throat swabs
were used to evaluate lower airway microorganisms. A throat swab and a
completed LRSQ after 3 months were received from 79 children with CP.
Most children had a GMFCS of I (24.1\%) or V (24.1\%). Feeding
difficulties, malnutrition, cough efficiency, airway clearance therapy
and epilepsy were statistically significant associated with GMFCS
stages. Twenty-eight patients (35\%) were found to have at least one
positive respiratory culture. Only 4 patients (5\%) were infected with
PA. Gram negative bacteria were isolated in 22\% of the positive throat
swabs, S. aureus was found in 14\%. Most pathogens were found in
patients with higher GMFCS score (GMFCS III, IV and V) (\emph{Table 2}
). Results of the LRSQ showed that 52\% of these patients reported
having 1 cold in the past 3 months. Only 3 patients were admitted to the
hospital, none of these patients were colonized with PA. No
statistically significant relation could be found between the number of
colds and/or pneumonia, the use of antibiotics or hospitalization,
and having a positive culture, colonization with S. aureus, P.
aeruginosa or gram-negative bacteria.

Although respiratory disease is an important risk factor for morbidity
and mortality in children with CP, we demonstrated that the prevalence
of PA in our population of children with CP without known chronic lung
disease is low. Despite several study limitations, colonization with PA
or other bacteria in a large sample of children with CP does not seem to
be a major cause of respiratory morbidity and mortality. Previous
studies, including the study by Gerdung et al. showed that children with
CP with a positive culture for gram-negative bacteria, and mainly PA,
had more severe respiratory disease, more Paediatric Intensive Care Unit
(PICU) hospitalizations, more need for mechanical ventilation, larger
pleural effusions and a longer hospitalization (2). Our study showed
that there is a correlation between GMFCS score and colonization with
gram-negative bacteria. The short-term respiratory consequences of being
colonized with these bacteria were limited in our prospective study. We
could not demonstrate a statistically significant correlation between
number of colds, pneumonia, the use of antibiotics or hospitalization
with having a positive culture, colonization with S. aureus, P.
aeruginosa or gram-negative bacteria. Possible explanations for this
could be the COVID-19 pandemic with two lockdowns and therefore less
exposure to pathogens due to less social contact and extensive hygienic
measures, no visitors in specialized day-care centers and closed
schools.

As we know life expectancy in CP can improve by both preventive
measurements as initiation of early therapy concerning respiratory
morbidity. The prevalence of PA in this prospective study of children
with CP is low, gram-negative bacteria were most commonly found.
Therefore, it is recommended to repeat and expand this study since the
prevalence of respiratory tract infections is again increasing in the
post-covid era.



\textbf{Table 1}

\textbf{Patient characteristics n = 79}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Age (years) & Mean & 8.44 (SD\textsuperscript{1} \selectlanguage{ngerman}±~ 4.74)\tabularnewline
Gender & M : F & 37 : 42\tabularnewline
Gross Motor Function Score & Level I & 19 (24.1\%)\tabularnewline
& Level II & 18 (22.8\%)\tabularnewline
& Level III & 9 (11.4\%)\tabularnewline
& Level IV & 14 (17.7\%)\tabularnewline
& Level V & 19 (24.1\%)\tabularnewline
\textbf{Respiratory characteristics} & &\tabularnewline
OSA\textsuperscript{2} & Yes : No & 4 : 75 (5.1\% :
94.9\%)\tabularnewline
Asthma & Yes : No & 2 : 77 (2.5\% : 97.5\%)\tabularnewline
Bronchiectasis & Yes : No & 1 : 78 (1.3\% : 98.7\%)\tabularnewline
Antibiotic prophylaxis & Yes : No & 3 : 76 (3.8\% :
96.2\%)\tabularnewline
Chronic respiratory medication\textsuperscript{3} & Yes : No & 9 : 70
(11.4\% : 88.6\%)\tabularnewline
Chronic airway clearance therapy (e.g. Physiotherapy) & Yes : No & 9 :
70 (11.4\% : 88.6\%)\tabularnewline
Chronic oxygen therapy & Yes : No & 1 : 78 (1.3\% :
98.7\%)\tabularnewline
NIV\textsuperscript{4} & Yes : No & 5 : 74 (6.3\% :
93.7\%)\tabularnewline
\textbf{Comorbidities} & &\tabularnewline
GER\textsuperscript{5} & Yes : No & 10 : 69 (12.7\% :
87.3\%)\tabularnewline
Feeding difficulties & Yes : No & 34 : 45 (43\% : 57\%)\tabularnewline
Malnutrition & Yes : No & 12 : 67 (15.2\% : 84.8\%)\tabularnewline
Scoliosis \emph{(missing n = 1)} & Yes : No & 7 : 71 (8.9\% :
89.9\%)\tabularnewline
Epilepsy \emph{(missing n = 1)} & Yes : No & 28 : 50 (35.4\% :
63.3\%)\tabularnewline
\bottomrule
\end{longtable}

\emph{TABLE 1 demographic characteristics. \textsuperscript{1}Standard
Deviation; \textsuperscript{2}Obstructive sleep apnea;~}

\emph{\textsuperscript{3}Chronic respiratory medication: Salbutamol,
Fluticasone propionate, Salmeterol/Fluticasone propionate,
Acetylcysteine;}

\emph{\textsuperscript{4}Non-invasive
ventilation;\textsuperscript{5}Gastroesophageal reflux~}

\textbf{Table 2}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
& \textbf{Positive culture of any bacteria} & \textbf{Positive culture
of any bacteria} & \textbf{Positive culture of any bacteria} &
\textbf{Gram-negative bacteria} & \textbf{Gram-negative bacteria} &
\textbf{Gram-negative bacteria} & \textbf{S. aureus} & \textbf{S.
aureus} & \textbf{S. aureus}\tabularnewline
\midrule
\endhead
& No & Yes & P value & No & Yes & \emph{P} value & No & Yes & \emph{P}
value\tabularnewline
\textbf{Predictors} & & & & & & & & &\tabularnewline
\textbf{GMFCS} & & & \textbf{.016} & & & \textbf{.006} & & &
\textbf{~~~~~ .040}\tabularnewline
~~~ I-II & 29 (36.7\%) & 8 (10.1\%) & & 34 (43.0\%) & 3 (3.8\%) & & 35
(44.3\%) & 2 (2.5\%) &\tabularnewline
~~~ III-IV-V & 22 (27.8\%) & 20 (25.3\%) & & 28 (35.4\%) & 14 (17.7\%) &
& 33 (41.8\%) & 9 (11.4\%) &\tabularnewline
\bottomrule
\end{longtable}

\emph{TABLE 2 Descriptive statistics and chi square tests for positive
culture, gram-negative bacteria, and S. aureus. A P-value \textless{}
0,05 is considered statistically significant.}



\textbf{References}

1. Boel L, Pernet K, Toussaint M, Ides K, Leemans G, Haan J, et al.
Respiratory morbidity in children with cerebral palsy: an overview. Dev
Med Child Neurol. 2019;61(6):646-53.

2. Gerdung CA, Tsang A, Yasseen AS, 3rd, Armstrong K, McMillan HJ,
Kovesi T. Association Between Chronic Aspiration and Chronic Airway
Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria
in Children with Cerebral Palsy. Lung. 2016;194(2):307-14.

3. Young NL, McCormick AM, Gilbert T, Ayling-Campos A, Burke T, Fehlings
D, et al. Reasons for hospital admissions among youth and young adults
with cerebral palsy. Arch Phys Med Rehabil. 2011;92(1):46-50.

4. Kuo TJ, Hsu CL, Liao PH, Huang SJ, Hung YM, Yin CH. Nomogram for
pneumonia prediction among children and young people with cerebral
palsy: A population-based cohort study. PLoS One. 2020;15(7):e0235069

5. Gibson N, Blackmore AM, Chang AB, Cooper MS, Jaffe A, Kong WR, et al.
Prevention and management of respiratory disease in young people with
cerebral palsy: consensus statement. Dev Med Child Neurol.
2021;63(2):172-82.

6. Silva Filho LV, Ferreira Fde A, Reis FJ, Britto MC, Levy CE, Clark O,
et al. Pseudomonas aeruginosa infection in patients with cystic
fibrosis: scientific evidence regarding clinical impact, diagnosis, and
treatment. J Bras Pneumol. 2013;39(4):495-512.

\textbf{Author names}

Katrien Romaen, MD\textsuperscript{1}*; Isabelle Van Ussel,
MD\textsuperscript{2}*; Carolin Van Rossem\textsuperscript{3}; Sandra
Kenis MD\textsuperscript{1}; Berten Ceulemans MD,
PhD\textsuperscript{1}; Kim Van Hoorenbeeck, MD, PhD\textsuperscript{4};
Stijn Verhulst MD, PhD\textsuperscript{4}

\textbf{Affiliations}

\textsuperscript{1} Department of Paediatric Neurology, Antwerp
University Hospital/University of Antwerp, Belgium.

\textsuperscript{2} Department of Paediatrics, AZ Voorkempen, Malle,
Belgium.

\textsuperscript{3} Department of Pediatrics, ZNA Queen Paola Children's
Hospital, Antwerp, Belgium.

\textsuperscript{4} Department of Paediatric Pulmonology, Antwerp
University Hospital and Lab of Experimental Medicine and Pediatrics,
University of Antwerp, Antwerp, Belgium.

* These authors contributed equally

\textbf{Conflict of interest statement}

No disclosure

\textbf{Correspondence}

Katrien Romaen, department of Pediatric Neurology, Antwerp University
Hospital. Drie Eikenstraat 655 2650 Edegem, Belgium.

E-mail: Katrien.romaen@uza.be

\selectlanguage{english}
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