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\begin{document}

\title{Early detection of laryngeal cleft in infants by novel technique of
flexible endoscopy with sustained pharyngeal inflation}



\author[1]{Wen-Jue Soong}%
\author[2]{Chia-Feng Yang}%
\author[3]{Pei-Chen Tsao}%
\author[4]{Yi-Hung Sung}%
\author[5]{Yen-Hui Soong}%
\affil[1]{Children's Hospital, China Medical University }%
\affil[2]{Taipei veterans general hospital}%
\affil[3]{Veteran general hospital, Taipei, Taiwan (ROC)}%
\affil[4]{Mackay Memorial Hospital}%
\affil[5]{Michigan State University College of Human Medicine}%


\vspace{-1em}



  
  \date{May 15, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: Report a novel technique of flexible endoscopy (FE) with
noninvasive ventilation (NIV) and sustained pharyngeal inflation
(FE-NIV-SPI) in assessing aeroesophageal tracts (AET) to facilitate
early detect laryngeal clefts (LC). Methods: Medical charts and FE
videos of the children who were diagnosed as LC in a tertiary care
hospital between 2000 and 2020 were retrospectively reviewed and
analyzed. FE-NIV-SPI technique was applied for all the reviewed
children. Results: Of all the FE videos reviewed, twelve infants with
laryngeal clefts were collected. This equates to a prevalence of 0.28\%
in all the children underwent FE at our institution. Their mean age was
5.0 \selectlanguage{ngerman}± 4.9 month-old and the mean body weight was 4.7 ± 2.3 kg. Nine
(75\%) infants were referred in without LC diagnosis, which was missed
by 11 prior bronchoscopy and 5 computer tomography exams. With
FE-NIV-SPI, the pharyngolaryngeal space could be pneumatically expanded
and allowed detailed assessment. All LC types and coexisted AET lesions
were visualized at the first FE-NIV-SPI examination with a mean time of
4.2 ± 0.9 minutes. They were eight type I, two type II and one type III.
Ten (83.3\%) infants coexisted airway malacia. Conclusion: Routinely
using the FE-NIV-SPI technique can help detect the LC defect and
associated AET lesions at the first assessment.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


Title pages

\textbf{Early detection of laryngeal cleft in infants by novel technique
of flexible endoscopy with sustained pharyngeal inflation}

\emph{\textbf{Wen-Jue Soong,\textsuperscript{\emph{1,2,3}}}
\textbf{Pei-Chen Tsao,\textsuperscript{\emph{2,3}}} \textbf{Chia-Feng
Yang,\textsuperscript{\emph{2,3}}} \textbf{Yi-Hung
Sung,\textsuperscript{\emph{4}}Yen-Hui Soong\textsuperscript{\emph{5}}}}

\emph{\textsuperscript{1}Division of Pediatric Pulmonology, Children's
Hospital, China Medical University, Taichung, Taiwan;}

\emph{\textsuperscript{2}Department of Pediatrics, Taipei Veterans
General Hospital, Taipei, Taiwan;}

\emph{\textsuperscript{3}Department of Pediatrics, School of Medicine,
National Yang Ming Chiao Tung University; Taipei, Taiwan;}

\emph{\textsuperscript{4}Pulmonary and critical care, Paloma Medical
Group; Los Angles, California, USA;}

\emph{\textsuperscript{5}Department of Medical Education, MacKay
Memorial Hospital, Taipei, Taiwan}

\textbf{Key words} : bronchoscopy, flexible endoscopy, flexible
laryngoscopy, laryngeal cleft, noninvasive ventilation, sustained
pharyngeal inflation, Soong's ventilation

\textbf{Abbreviated title:} \emph{Flexible endoscopy with sustained
pharyngeal inflation detect laryngeal cleft}

Corresponding (reprint request) author:

\textbf{Wen-Jue Soong, MD}

Division of Pediatric Pulmonology, China Medical University Children's
Hospital, Taichung, Taiwan.

No. 2, Yuh-Der Road, Taichung 40447, Taiwan.

Phone: +886-4-22052121 ext. 4648;

Fax.: +886-4-22032798;

Cell phone: +886-921067989;

E-mail: wjsoong3@\emph{gmail.com}

\textbf{Financial disclosure:}

\begin{itemize}
\tightlist
\item
  This study was \emph{granting supported} and \emph{IRB proved} by
  Taipei-Veterans General Hospital (VGHIRB: No. 2018-11-002BC).
\item
  There is no support from any commercial manufacture or company about
  this study.
\item
  The first author, \emph{Wen-Jue Soong,} wrote the first draft of the
  manuscript.
\item
  Report to \emph{Pediatric Pulmonology} : on behalf of all authors, the
  corresponding author states that there is no conflict of interest with
  any person or company.
\end{itemize}

\textbf{Authors list}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Name}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Highest academic degree}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{E-mail}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Contribution statement}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Affiliation}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Wen-Jue Soong\textsuperscript{1,2,3}}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD.\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{wjsoong3@gmail.com} Orcid id: 0000-0002-8397-4956\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Conceptualization, Methodology, Investigation, Resources,
Writing-original draft, Supervision\ldots{}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Division of Pediatric Pulmonology Children's Hospital, China Medical
University Taichung, Taiwan. Department of Pediatrics, Taipei Veterans
General Hospital, Taipei; School of Medicine, National Yang-Ming
University; Taipei, Taiwan Department of Medical Education, Taipei
Veterans General Hospital, Taipei, Taiwan Paloma Medical Group, Los
Angles, California, USA;\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Pei-Chen Tsao\textsuperscript{2,3}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD, PhD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{tsao3840@gmail.com} Orcid id: 0000-0003-1613-653\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Investigation, Project administration,\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Chia-Feng Yang\textsuperscript{2,3}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD, PhD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{pum\_chia@yahoo.com.tw} Orcid id: 0000-0001-5739-5216\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Software, Formal analysis,\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Yi-Hung Sung\textsuperscript{4}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{yheddysung@gmail.com} Orcid id: 0000-0002-8423-5223\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Writing-review \& editing\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Yen-Hui Soong\textsuperscript{5}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
msoongy@gmail.com Orcid id: 0000-0001-8640-8784\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Validation, Writing-review \& editing\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{}

\textbf{Introduction}

Laryngeal cleft (LC), a fissure defect between laryngotrachea and upper
esophagus, is a rare congenital anomaly occurring in less than 0.1\% of
the general population.\textsuperscript{1-3} LC is important to be early
recognized to prevent unnecessary diagnostic work-up, medication and
associated morbidities. The main presenting symptoms of stridor, chronic
cough and recurrent aspiration are non-specific. Direct visual
confirming its presence and identifying type are clinically challenging.
Rigid endoscopy (RE) is capably separating and inspecting
inter-arytenoids and hypopharyngeal region, therefore, being recommended
as confirmatory diagnosis of LC.\textsuperscript{3-7} However, due to
the need for general anesthesia, lack of RE expertise in many centers,
the application of RE can be challenging in common practices for
diagnosing LC.

Flexible endoscopy (FE) allows direct inspection of the dynamic
structures of pharyngolaryngeal space (PLS) and aeroesophageal tracts
(AET), therefore is the preferred first-line visual
examination.\textsuperscript{8,9} However, defects in the posterior
larynx may not be readily noticeable due to the inherent collapse
hypopharynx, which usually displays a normal appearance. Even with
apparent symptoms and a high index of suspicion, LC could still be
overlooked by experienced operator using traditional FE
technique.\textsuperscript{3,10,11} Trachsel's group published a report
of FE assisted with using continuous positive airway pressure via an
endoscopy face mask for the diagnosis of LC.\textsuperscript{12} We here
like to share our experiences by applying a more simple technique of
positive airway pressure (PPV) to evaluate LC.

``Pharyngeal oxygen with optional nose-closure and abdomen-compression
(PhO\textsubscript{2}-NC-AC)'' is a novel technique of noninvasive
ventilation (NIV).\textsuperscript{13-15} Clinically, it is a safe and
convenient method of producing PPV without using any ventilation or
airway devices of Ambu-bag, face mask, nasal prong, laryngeal mask
airway, endotracheal tube or ventilator. FE with this NIV (FE-NIV) can
ensure adequate oxygenation during many interventional procedures of AET
in pediatrics, even in severe asphyxiated
status.\textsuperscript{16-18}In this NIV, maneuvers of prolonged
nose-closure, 1 to 5 second, can create sustained pharyngeal inflation
(SPI) with enough, dynamic and controllable PPV to expand the PLS and
allows precise FE assessment.\textsuperscript{19} Over the last two
decades, we have routinely using this FE-NIV and SPI (FE-NIV-SPI)
technique and have successfully detected many LC lesions at their first
FE inspection of larynx.

We like to share our experiences using this novel FE-NIV-SPI technique
alone to screen for LC lesions and report characteristics of our
patients.

\textbf{Methods}

A retrospective study was conducted in Taipei Veterans General Hospital,
a tertiary care medical center. Many pediatric patients in Taiwan and
surrounding countries with complex airway diseases needing bronchoscopy
interventions evaluation. FE number was 400 to 500 per year in the last
two decades. Medical charts and associated FE videos of pediatric
patients who were diagnosed of LC between January 2000 and December 2020
were reviewed and enrolled in this study. Their demographic and clinical
data were collected and analyzed. This study was approved by the
Medico-Ethical Committee of hospital (VGHIRB: No. 2018-11-002BC).

\textbf{FE-NIV preparation}

FE patients followed a standard preparation. Procedural sedation of
intravenous midazolam 0.1-0.2mg/kg, ketamine 1-2mg/kg and atropine
0.01mg/kg was given to keep patient motionless yet still maintain
spontaneous breathing. Topical anesthesia of 2\% lidocaine solution, 1.0
ml/kg, was applied via syringe catheter into patient's nostrils and
trachea. A continuous oxygen flow (1.0 L/Kg/min, maximal 10.0 L/min)
delivered through a small nasopharyngeal catheter as the ``pharyngeal
oxygen, PhO\textsubscript{2}''. PhO\textsubscript{2}-NC-AC technique was
routinely used to ensure adequate oxygenation and ventilation during the
entirety of FE procedure. Vital signs including heart rate, respiration,
oxygen saturation and blood pressure were continuously monitored.

FE performed with a short working-length (30 cm) flexible endoscope,
outer diameter 2.6 mm or 3.2 mm (Olympus, ENF-V2 or ENF-V3), without
inner cannel. Flexible bronchoscope was introduced into the nasal tract
and advanced into the supraglottic region. With chin lift maneuver, the
entire larynx including the epiglottis, arytenoids, vocal cords and
hypopharynx could be visualized. (Figure 1a) During nose-open phase, the
posterior laryngeal commission and hypopharyngeal wall may appose each
other and resulted a collapsed esophageal inlet.

\textbf{FE-NIV-SPI assess AET}

During FE-NIV assessment, SPI was optionally done by right hand of
operator (Figure 1b) with index finger hooked patient's chin to pull and
close patient's mouth, thumb and mid-finger pinch-closed patient's nose.
SPI of 1 to 5 seconds, as required, was applied to gradually inflate and
expand spaces of supraglottis and hypopharynx for clear FE
inspection.\textsuperscript{19} In case of LC, a deep fissure over the
posterior larynx could be observed. The size of the defect and its
relationship with surrounding structures were measured by manipulating
scope tip or using forceps. The scope was then advanced into the
tracheobronchial and the esophageal lumens for further evaluation. Types
of LC were based on the Benjamin and Inglis
classification.\textsuperscript{20} SPI maneuver with duration of 3 to 5
seconds could be repeated as necessary. Between each SPI, patient was
allowed spontaneous breaths or supported with NIV for at least 10
seconds. The time of making a complete diagnosis, from insertion of
endoscope to final confirmation of the LC type, was captured from the
video recording.

After completion of FE procedure, abdomen compressions and gastric
suctions were routinely performed to eliminate air distention. A
post-procedural chest radiography was routinely checked for possible
complications of air leak or damages.

\textbf{RESULTS}

Over the 20-year period, a total of 8,125 FE procedures of AET were
performed in 4,227 patients. Among them, 12 infants (7 male, 58.3\%) had
a diagnosis of LC, with an incidence of 0.28\% in our FE patients. Of
these infants, 8 was type I, 3 was type II, and 1 was type III (Table
1). These LC diagnosis were all made in their first FE-SPI examination.
The type III LC was further confirmed with RE. At the time of FE
diagnosis, their mean age was 5.0 \selectlanguage{ngerman}± 4.9 (ranged from 6 hours to 18
months) months old, the mean body weight was 4.7 ± 2.3 (ranged from 2.7
to 10.6) kg.

Nine (10/12, 83.3\%) infants were referred from other hospitals,
included 7 infants from 6 tertiary children's hospitals and 2 infants
from neighboring countries, for management of their refractory
respiratory problems. Among them, before admitted to our hospital, 7
infant's airway were already examined with 11 FE and 5 computed
tomography studies, no LC was found. Nine infants had failure to thrive.
Four infants had tracheal intubation and 3 had prolonged mechanical
ventilation support due to pneumonia, respectively. All 12 FE-SPI
procedures were performed within three hours of admission.

Under FE-SPI inspection, the whole PLS could be gradually lifted and
clearly visualized. In particular supraglottis, bilateral arytenoids
with redundant tissue and cleft itself could be pneumatically separated
and precisely identify its type, included depths of the cleft. All the
LC lesions of these 12 infants were successfully recognized at their
first FE-SPI examination of the larynx before checking the tracheal or
esophageal lumens. The time for a complete diagnosis of LC ranged from
3.0 to 5.5 minutes, with a mean of 4.2 ± 0.9 minutes. Ten (90.9\%)
infants coexisted with airway abnormalities including 9 infants (9/12,
75.0\%) with laryngomalacia and 3 infants (3/12, 25.0\%) with tracheal
or bronchial malacia. Four infants (4/12, 25.0\%) had coexisting
gastroesophageal reflux.

All infants tolerated the FE-SPI procedure. No associated complications
such as oxygen desaturation (\textless{} 90\%), bradycardia (heart beat
\textless{}100/min), ear drum perforation, subcutaneous air leak,
pneumothorax or AET bleeding were noted.

\textbf{DISCUSSION}

FE-NIV-SPI is a safe and simple technique that can be routinely applied
under common procedural setting to detect LC in infants. The usage of
nasopharyngeal catheter to deliver continuous oxygen flow and
application of nose-closure maneuver to generate airway pressure to
expand PLS and AET lumens, allowing detailed visualization of the LC.

Hypoxia and hypoventilation are frequent complications of pediatric FE
interventions, therefore the usage of supplemental oxygen and PPV are
highly recommended.\textsuperscript{21-23} Without pneumatic stenting of
SPI, as traditional method of FE, hypopharynx, posterior larynx and
upper esophagus remain collapsed and the LC may otherwise stay
undetected. Over the past two decades, we have incorporated FE-NIV-SPI
technique as the default method to maintain oxygenation and ventilation
in our endoscopic practice. This allows us to perform many bronchoscopic
interventions that otherwise cannot be safely performed in infants with
severe asphyxia condition.\textsuperscript{13-19} If FE-NIV-SPI is
routinely applied in all FE, this review suggest that it may detect more
LC at the first laryngeal examination. Although the deeper involved
lesions, such as type IV, may still need a RE to confirm, the most
commonly types of I, II and III LC defects can be diagnosed reliable
with FE-NIV-SPI. That may allow waiving more invasive and complicated
procedures of RE, general anesthesia and radiologic examinations.

For LC, an early diagnosis is crucial for subsequent management to
prevent morbidity or mortality. Traditionally, being widely available
and easily handled, FE plays an essential role in exploring lesions that
cause airway and respiratory problems in pediatric
patients.\textsuperscript{24-26} However, FE has not been considered a
commendable tool to evaluate the posterior commissure of the larynx
where lesion as LC may fail to recognize.\textsuperscript{27} RE is more
capable and remains the gold standard for confirmation of
LC.\textsuperscript{3-7} However, there may have technical difficulties
and risky, especially in small infants who already have respiratory
distress, need transfer to operation room and receive general
anesthesia. Their short oral cavity limits in securing the RE
instrument. The review suggests that these disadvantages can be
effectively counteracted by the application of FE-NIV-SPI, especially in
type I, II and III LC.

SPI with simultaneous chin-lift help to pneumatically expand the PLS
including larynx, hypopharynx, esophageal inlet and upper esophagus. In
our prior study\textsuperscript{19} of identical setting, the SPI with
duration of 0 to 5 seconds could create linear correlated positive
pressure levels from 4.1±3.3 to 65.5±18.5 cmH\textsubscript{2}O in PLS.
When the nose was open (SPI 0 second), the intra-PLS pressure around
4.1±3.3 cmH\textsubscript{2}O, the surrounding structures were
relatively collapse included the posterior glottis space. LC may be
inadvertently overlooked as a result of redundant mucosa between
esophagus and trachea apposing each other and sealing the cleft (Figure
2a), as those seven referred infants had done FE in the traditional way.
During the SPI, the intra-PLS pressure gradually rising and sustaining
up to 60 cmH\textsubscript{2}O, which were high enough to open the
collapsed lumens of AET and the esophageal sphincter. These dynamic
changes of pressure levels could be optionally and safely controlled by
operator. The LC, if existed, could be well visualized (Figure 2b, c),
probed and dispersed with the tip of FE or forceps to assess the depth
and grading the cleft. The whole AET lumens, included trachea and
esophagus, could be detail investigated. These dynamic events allowed
for repeat and precise evaluation by FE.

This FE-NIV-SPI technique provides several advantages. 1) Oxygen
insufflation alone through the nasopharyngeal catheter can flush upper
airway dead space, as the effects of ``apneic
oxygenation'',\textsuperscript{28-30} which can significantly prolong
onset of desaturation. 2) Both assist inspiration and expiration can be
achieved by simple maneuvers of nose-closure and abdomen-compression,
respectively, to provide adequate oxygenation and PPV. 3) No other
supplemental instruments such as mask, endotracheal tube, ventilation
bag, or ventilator are needed, therefore it is cost-effective, eliminate
procedural time and provide an unimpeded field for FE manipulation. 4)
In addition to the LC, other coexisted lesions such as
laryngomalacia,\textsuperscript{6} vallecular
cyst,\textsuperscript{18,I9} trachea, bronchial or esophageal
pathologies also can be detected and managed in the same FE
session.\textsuperscript{16,17} 5) Furthermore, it facilitates
therapeutic interventions\textsuperscript{15-18} such as laser ablation,
balloon measurement, stent implantation and repair in cardiopulmonary
compromised children.

There are limitations in this study. 1) Although FE-NIV-SPI is easy for
detecting most type I, II, and III LC, severe type IV LC may difficult
to fully visualize and not with diagnostic certainty. Confirmatory RE is
still necessary to determine the deeper cleft length and guide the
management approach, as it remains the gold diagnostic standard. 2)
Although the technique of FE-NIV-SPI have previously been
reported,\textsuperscript{13-15} this may still be unfamiliar to many
pediatric pulmonologists. Repetitive practice of this technique may be
necessary to develop skill competency. 3) This report is from one single
institution experience and the case number may not enough to make
definitive conclusion. For this rare incidence and occult lesion of LC,
further multi-center cooperative investigations are needed to verify the
early detection with this FE-SPI technique.

\textbf{CONCLUSION}

Routine application of the FE-NIV-SPI technique for AET assessment could
safely and rapidly detect the LC lesion at the first laryngeal
inspection in infants. That may avert using other complicated diagnostic
instruments.

\textbf{ACKNOWLEDGMENTS}

The study was supported by the Taipei Veterans General Hospital
(2018-11-002BC) and the Medicine and Institute of Emergency and Critical
Care Medicines, Medical School, National Yang-Ming Chiao-Tung
University, Taiwan.

\textbf{Declaration of interest}

All authors declare that there is no any con\selectlanguage{english}flict of interests regarding
the publication of this paper.

End.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Moungthong G, Holinger L. Laryngotracheoesophageal clefts. \emph{Ann
  Otol Rhinol Laryngol} . 1997;106(12):1002--1011
\item
  Narcy P, Bobin S, Contencin P, et al. Laryngeal anomalies in newborn
  infants: apropos of687 cases. \emph{Ann Otolaryngol Chir Cervicofac} .
  1984;101(5):363--373 {[}in French{]}.
\item
  Roth B, Rose KG, Benz-Bohm G, Gunther H. Laryngotracheoesophageal
  cleft: clinical features, diagnosis and therapy. \emph{Eur J Pediatr}
  . 1983;140(1):41--46
\item
  Neubauer PD, Rosenthal LS, Drake AF, Zdanski CJ, Shah RN. Rigid
  Laryngoscopy Is Necessary to Diagnose Laryngeal Cleft. Otolaryngology
  -- Head and Neck Surgery. 2011;145(2): P245 doi:
  10.1177/0194599811415823a360
  http://oto.sagepub.com/content/145/2\_suppl/P245.2
\item
  Rahbar R, Rouillon I, Rogers G, et al. The presentation and management
  of laryngeal cleft: a 10-year experience. Arch Otolaryngol Head Neck
  Surg. 2006;132(12):1335--1341
\item
  Glossop LP, Smith RJ, Evans JN. Posterior laryngeal cleft: an analysis
  of ten cases. Int J Pediatr Otorhinolaryngol. 1984;7(2):133--143
\item
  Chien W, Ashland J, Haver K, Hardy SC, Curren P, Hartnick CJ. Type 1
  laryngeal cleft: establishing a functional diagnostic and management
  algorithm. Int J Pediatr Otorhinolaryngol. 2006;70(12):2073--2079
\item
  Langmore SE. Evaluation of oropharyngeal dysphagia: which diagnostic
  tool is superior? \emph{Curr Opin Otolaryngol Head Neck
  Surg.}2003;11(6):485--489
\item
  Pezzettigotta SM, Leboulanger N, Roger G, et al. Laryngeal
  cleft.\emph{Otolaryngol Clin North Am.} 2008;41(5):913--933
\item
  Eriksen C, Zwillenberg D, Robinson N. Diagnosis and management of
  cleft larynx: literature review and case report. Ann Otol Rhinol
  Laryngol. 1990;99(9 Pt 1 ):703--708
\item
  Parsons DS, Herr T. Delayed diagnosis of a laryngotracheoesophageal
  cleft. Int J Pediatr Otorhinolaryngol. 1997;39(2):169--173
\item
  Daniel Trachsel D, Hammer J. CPAP to diagnose laryngeal clefts by
  flexible endoscopy in infants. Pediatr Pulmonol 2018
  Sep;53(9):1284-1287. doi: 10.1002/ppul.24117
\item
  Soong WJ, Jeng MJ, Lee YS, Tsao PC, Harloff M, Soong YH. A novel
  technique of non\selectlanguage{english}-invasive ventilation: pharyngeal oxygen with
  nose\selectlanguage{english}-closure and abdominal\selectlanguage{english}-compression\selectlanguage{english}-aid for pediatric flexible
  bronchoscopy. Pediatr Pulmonol. 2015;50:568\selectlanguage{english}-575.
\item
  Peng YY, Soong WJ, Lee YS, Tsao PC, Yang CF, Jeng MJ. Flexible
  bronchoscopy as a valuable diagnostic and therapeutic tool in
  pediatric intensive care patients: a report on 5 years of experience.
  Pediatr Pulmonol. 2011;46:1031\selectlanguage{english}-1037.
  https://doi.org/10.1002/ppul.21464
\item
  Soong WJ. Pediatric interventional flexible bronchoscopy. Pediatr
  Respiro Crit Care Med. 2018;2:38\selectlanguage{english}-44.
\item
  Soong WJ, Tsao PC, Lee YS, Yang CF. Flexible endoscopy for pediatric
  tracheobronchial metallic stent placement, maintenance and long\selectlanguage{english}-term
  outcomes. PLoS One. 2018;13:e0192557.
  https://doi.org/10.1371/journal.pone.0192557
\item
  Soong WJ, Tsao PC, Lee YS, Yang CF. Therapeutic flexible airway
  endoscopy of small children in a tertiary referral center---11 years'
  experience. PLoS One. 2017;12(8):e0183078.
  https://doi.org/10.1371/journal.pone.0183078
\item
  Soong WJ, Yang CF, Lee YS, Tso PJ, Lin CH, Chen CH. Vallecular cyst
  with coexisting laryngomalacia: successful diagnosis and laser therapy
  by flexible endoscopy with a novel noninvasive ventilation support in
  infants. Ped Pulmonol. 2020;55:1\selectlanguage{english}-7. https://doi.org/10.1002/ppul.24796
\item
  Soong W, Chen C, Lin C, Yang CF, Lee YS, Tsao PC, Sung YH, Dhochak N.
  Sustained pharyngeal inflation on upper airway effects in
  children---Flexible bronchoscopy measurement. Pediatric Pulmonology.
  2021;1\selectlanguage{english}-8. https://doi.org/10.1002/ppul.25608
\item
  Benjamin B Inglis A. Minor congenital laryngeal clefts: diagnosis and
  classification. Ann Otol Rhinol Laryngol 1989; 6: 417--420.
\item
  Schnapf BM. Oxygen desaturation during fiberoptic bronchoscopy in
  pediatric patients. Chest1991;99(3):591--594
\item
  Prakash UB, Offord KP, Stubbs SE. Bronchoscopy in North America: the
  ACCP survey. Chest1991;100(6):1668--1675
\item
  Honeybourne D, Neumann CS. An audit of bronchoscopy practice in the
  United Kingdom: a survey of adherence to national guidelines. Thorax.
  1997;52(8):709--713
\item
  Woodhull S, Goh EN, Lin TP, Chay OM. Pediatric flexible bronchoscopy
  in Singapore: a 10-year experience. J Broncho \& Intervent Pul.
  2010;17(2):136--141
\item
  Lee YS, Soong WJ, Jeng MJ, Cheng CY, Shen CM, Sun J, Chen CF, Hwang B.
  Flexible endoscopy of aerodigestive tract in small infants. Pediatric
  Internat. 2003;45(5):530--533
\item
  Chen WT, Soong WJ, Chang HL, Lee YS, Jeng MJ, Hwang B. The safety of
  aerodigestive tract flexible endoscopy as an outpatient Procedure in
  young children. JCMA. 2008;71(3):128--134
\item
  Wood RE. Evaluation of the upper airway in children. Curr Opin
  Pediatr. 2008;20:266--271.
\item
  Soneru CN, Hurt HF, Petersen TR, Davis DD, Braude DA, Falcon RJ.
  Apneic nasal oxygenation and safe apnea time during pediatric
  intubations by learners. Paediatr Anaesth. 2019;29:628\selectlanguage{english}-634.
  https://doi.org/10.1111/pan.13645
\item
  Riva T, Seiler S, Stucki F, Greif R, Theiler L. High\selectlanguage{english}-flow nasal
  cannula therapy and apnea time in laryngeal surgery. Paediatr Anaesth.
  2016; 26:1206\selectlanguage{english}-1208.
\item
  Steiner JW, Sessler DI, Makarova N, et al. Use of deep laryngeal
  oxygen insufflation during laryngoscopy in children: a randomized
  clinical trial. Br J Anaesth. 2016;117:350\selectlanguage{english}-357.
\end{enumerate}



\textbf{Legends}

\textbf{Figure 1.} Illustrations show flexible laryngoscopy with nasal
pharyngeal oxygen. Laryngeal cleft cannot be detected during nose-open
(a), but it become obvious gradually during sustained pharyngeal
inflation by doing nose-closure (b).

\textbf{Figure 2.} Serial images of Laryngeal cleft (LC) with different
durations of sustained pharyngeal inflation (SPI); nearly normal at SPI
of 0 to 1 second (a) and the cleft gradually become obvious at 3 to 5
seconds (b, c).

End.\selectlanguage{english}
\begin{figure}[H]
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\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/Fig-2a,b,c/Fig-2a,b,c}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table 1--202110.docx`  available at \url{https://authorea.com/users/370890/articles/544071-early-detection-of-laryngeal-cleft-in-infants-by-novel-technique-of-flexible-endoscopy-with-sustained-pharyngeal-inflation}

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