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\begin{document}

\title{Flexible endoscopy with noninvasive ventilation assesses and manages
infants with severe bronchopulmonary dysplasia}



\author[1]{Wen-Jue Soong}%
\author[2]{Pei-Chen Tsao}%
\author[3]{Chia-Feng Yang}%
\author[2]{Yu-Sheng Lee}%
\author[4]{Chieh-Ho Chen}%
\author[5]{Chien-Heng Lin}%
\author[2]{Yi-Hung Sung}%
\affil[1]{Children's Hospital, China Medical University }%
\affil[2]{Taipei Veterans General Hospital}%
\affil[3]{Taipei veterans general hospital}%
\affil[4]{China Medical University}%
\affil[5]{China Medical University Hospital}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objectives Flexible endoscopy (FE) assessed the whole approachable
aeroesophageal (AE) tracks and changes of management in infants with
severe bronchopulmonary dysplasia (sBPD). Methods A 10 years (2011-2020)
retrospective study of sBPD infants who had FE with and without
artificial airway in AE tracks. FE with noninvasive ventilation (FE-NIV)
of pharyngeal oxygen with nose-close and abdomen-compression was
supported. Data of found pathologies, changes of consequent management
and therapeutic interventions were collected and analyzed. Results Total
42 infants enrolled. Two scopes of 1.8mm and 2.6mm were used. FE
revealed 129 AE pathologies in 38 (90.5\%) infants. Twenty-eight
(66.7\%) infants detected more than one lesion. In 35 (83.3\%) infants
with 111 airway lesions, bronchial granulations (28, 25.2\%),
tracheomalacia (18, 16.2\%) and bronchial granulations (15, 13.5\%) were
the leadings. Fifteen (35.7\%) infants had 18 esophageal lesions. No
significant FE-NIV complication noted. FE findings resulted consequent
changes of management in all 38 infants. Thirty-six (85.7\%) infants
involved respiratory care of pressure titrations (29, 45.3\%), shorten
suctioning depth (17, 26.6\%), changed endotracheal or tracheostomy tube
depth (10, 15.6\%) and extubation (8, 12.5\%). Twenty-one (50\%) infants
had 50 medication changes included add steroids, anti-reflux medicine,
antibiotics and stop antibiotics. Eighteen (42.8\%) infants had received
37 therapeutic FE-NIV procedures which included 14 balloon dilatation,
13 laser-plasty and 10 stent implantations. Seven (16.7\%) infants had
surgeries included 4 tracheostomies and 3 fundoplications. Conclusion
FE-NIV can be a safe and valuable modality for direct visual assessment
of AE pathologies which contributed subsequent changes of clinical
management in sBPD infants.%
\end{abstract}%



\sloppy


Title pages

\textbf{Flexible endoscopy with noninvasive ventilation assesses and
manages infants with severe bronchopulmonary dysplasia}

Wen-Jue Soong\textsuperscript{1,2,3} , Pei-Chen
Tsao\textsuperscript{2,4}, Chia-Fang Yang\textsuperscript{2,4}, Yu-Sheng
Lee\textsuperscript{2,4}, Chien-Heng Lin\textsuperscript{1}, Chieh-Ho
Chen\textsuperscript{1}, Yi-Hung Sung\textsuperscript{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, Tri-Service General
Hospital, National Defense Medical Center, Taipei, Taiwan;}

\emph{\textsuperscript{4}Department of Pediatrics, School of Medicine,
National Yang-Ming Chiao Tung University; Taipei, Taiwan;}

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

\emph{\textbf{Abbreviated title:} Bronchoscopy effects in severe BPD
infants}

\textbf{Key words} : Bronchopulmonary dysplasia, flexible bronchoscopy,
premature infant, noninvasive ventilation, Soong's ventilation

Corresponding 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: \emph{wjsoong3@gmail.com}

\textbf{Financial disclosure:}

\begin{itemize}
\tightlist
\item
  This study was approved by Ethical committee review board
  of\emph{Taipei Veterans General Hospital} (IRB-TPEVGH
  No.:2021-08-015BC).
\item
  There is no support from any 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{Authorship 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{Affiliations}\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
\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, Tri-Service General Hospital, National Defense Medical
Center, Taipei, Taiwan;} \emph{\textsuperscript{4}School of Medicine,
National Yang-Ming University; Taipei, Taiwan;}
\emph{\textsuperscript{5}Department of Medical Education, MacKay
Memorial Hospital, Taipei, Taiwan;}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Pei-Chen Tsao\textsuperscript{2,4}}\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\ldots{}\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{2,4}\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{Cfyang3@vghtpe.gov.tw} Orcid id: 0000-0001-5739-5216\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Investigation, Project administration\ldots{}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Yu-Sheng Lee\textsuperscript{2,4}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
PhD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{leeys@vghtpe.gov.tw} Orcid id: 0000-0003-0438-0082\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Investigation, Project administration\ldots{}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Chien-Heng Lin\textsuperscript{1}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{Lch227@ms39.hinet.net} Orcid id: 0000-0002-9278-5911\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Investigation, Project administration\ldots{}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{Chieh-Ho Chen\textsuperscript{1}}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
MD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{pedlungcmu@gmail.com} Orcid id: 0000-0003-4486-7464\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Investigation, 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
\textbf{Yi-Hung Sung\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
\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
\bottomrule
\end{longtable}



\textbf{Flexible endoscopy with noninvasive ventilation assesses and
manages infants with severe bronchopulmonary dysplasia}

\textbf{Background}

Successful management of severe bronchopulmonary dysplasia (sBPD)
requires a multidisciplinary approach to optimize respiratory care,
proper pharmacotherapy, adequate nutrition, offer appropriate
interventions and search for comorbidities. Much importance is placed on
identifying the pathologies in each infant with sBPD and accordingly
adjust their individualized managing strategies in an evidence-based
fashion. Flexible endoscopy (FE) is a well-established and safe tool for
direct visual inspection and evaluation of dynamic aero-esophageal (AE)
anomalies for patients in the endoscopy room or intensive care unit
(ICU) setting.\textsuperscript{1-3} Infants with sBPD typically have
prolonged hospitalization course requiring numerous invasive managing in
the AE tract which include invasive positive pressure ventilation (PPV),
multiple attempts of intubation and extubation of endotracheal tube (ET)
and feeding tube, noninvasive ventilation (NIV) and airway suctioning
during hospitalization.\textsuperscript{4,5} As result, they are
vulnerable and risky for iatrogenic AE lesions such as subglottic
stenosis, tracheomalacia (TM), bronchomalacia
(BM)\textsuperscript{6-8}and gastroesophageal reflux disease
(GERD).\textsuperscript{9-11}Studies reported that only less than 5\% of
patients with BPD had normal airway evaluations.\textsuperscript{12}
Thus, it is important to perform a detailed FE of AE tract so that
pathologies can be fully identified. However, the existed AE anomalies
and associated cardiopulmonary dysfunction remain challenging for
performing the invasive FE procedures and consequent FE-related
interventions.

``Pharyngeal oxygen with optional nose-closure and abdomen-compression
(PhO\textsubscript{2}-NC-AC)'' is a novel model of NIV with advantages
of providing PPV without using artificial device such as Ambu-bag, face
or nasal mask, laryngeal mask airway, ET or mechanical ventilator.
Previous studies have demonstrated its efficacy in providing adequate
oxygenation and ventilation during FE assessment of entire AE tract in
pediatric patients with risk of hypoxemia or even respiratory
failure.\textsuperscript{13-17} To our knowledge, there is no study
dealing the modality of FE with this NIV (FE-NIV) support to evaluate
infants with sBPD.

The primary objectives of this study were 1) to describe the diagnostic
findings of FE-NIV for assessment of AE lumens and 2) the resultant
changes in clinical management of infants with sBPD.

\textbf{Methods}

This was a 10-years retrospective review of infants with sBPD at a
tertiary and transferred medical center, \emph{Taipei Veterans General
Hospital} in Taiwan, who underwent FE from January 2011 to December
2020. Only FE performed after made sBPD diagnosis during the
hospitalization were included for this analysis. Written informed
consent was obtained from parents/legal guardians before the FE
procedure. Ethical committee review board of hospital approved this
study (IRB-TPEVGH No.:2021-08-015BC).

Patient enrolled

Patients were diagnosed with sBPD if they met the following
criterias\textsuperscript{7} described by National Institute of Child
Health and Development (NICHD). An infants is diagnosed with sBPD if 1)
born prior to 32 weeks postmenstrual age (PMA) and required supplemental
oxygen for [?]28 days and [?]30\% oxygen concentration or PPV at 36 weeks
PMA, 2) born after 32 weeks gestational age and prior to 37 weeks
gestational age who required supplemental oxygen for [?]28 days and [?]30\%
oxygen concentration or PPV at 56 days of life. As the use high flow
nasal cannula (HFNC) was not specified, infants born prior to 32 weeks
PMA or born after 32 weeks but prior to 37 weeks PMA were defined as
having sBPD if on \textgreater{}2 LPM with any inspired oxygen at 36
weeks PMA or 56 days of life respectively. Failure of extubation was
defined by a need for re-intubation within 48 hours of extubation.
Infants with congenital cardiovascular disease were excluded from this
study.

Patient preparation

All FE's were performed at bedside of neonatal intensive care unit (ICU)
or Pediatric ICU. Procedural sedation was administered with intravenous
midazolam (0.1-0.2mg/kg) with or without ketamine (1-2 mg/kg) while
maintaining spontaneous breathing. Topical anesthesia of 2\% lidocaine
solution (1-2 ml/kg) was applied via ET into distal airways. For infants
without ET or just extubation, the lidocaine solution was applied into
nostrils, larynx and tracheal lumen with a syringe catheter (a trimmed
suction catheter attached to a 5-ml syringe) under rigid laryngoscopy.
Continuous vital signs, including non-invasive blood pressure every 5
minutes, were monitored throughout the FE-NIV procedure.

NIV support

Infant's original respiratory devices including nasal cannula, nasal
prongs, artificial airway and mechanical ventilator, if presented, were
replaced with the following NIV support. The tracheostomy stoma, if
presented, was sealed closely sealed with tape.

NIV support using PhO\textsubscript{2}-NC-AC
approach\textsuperscript{13,15} throughout the whole FE course which was
described below. A continuous, warmed and humidified pure oxygen flow
(1.0 L/kg/min) was delivered through a nasopharyngeal catheter
(preferably right nostril) to fill the upper airway cavity. In this NIV,
sustained pharyngeal inflation (SPI) with duration of nose-closure (NC)
of 0 to 3 seconds was optionally applied. With infant's mouth closed by
hooking endoscopist's right index finger at submental bone, following
maneuvers were performed to deliver the PPV: (1) Inspiration phase was
accomplished by NC with thumb and mid-finger (Figure 1a). Cricoid
pressure might also be applied concurrently with endoscopist's
ipsilateral little finger. SPI was performed for 0 to 3 seconds. (2)
Expiration phase (Figure 1b) was started passively with the release of
NC and cricoid pressure, which could be facilitated with simultaneous
abdomen-compression (AC) over umbilical region. Above steps were
performed optionally at a rate of 5--10 cycles per minute. Endoscopist
could simultaneously doing both the FE and NC (release) maneuver, while
an assistant (if present) might give the AC (release).

Flexible endoscopy

FE-NIV performed in the following routes.

\begin{enumerate}
\tightlist
\item
  For infants with invasive airways (ET or tracheostomy tube), FE
  proceeded directly via the invasive airway checking lumens inside and
  beyond the tip. Then, extubated and did FE again as below.
\item
  For infants without invasive airway (or after extubation), FE was
  performed via the nostril (left) and examined down to all-approachable
  distal bronchial lumens.
\item
  Finally, the scope withdrew back to pharynx, re-cannulated and
  assessed the esophagus and stomach.
\end{enumerate}

After FE-NIV assessment, infants remained in the ICU care for consequent
clinical management.

Data abstraction and analysis

Infants' characteristics and information were collected from the
electronic medical records. Gross findings of the AE tract and
associated complications were obtained from the FE reports. Airway
malacia was diagnosed when there was greater or equal to 50\% reduction
in the luminal diameter during spontaneous breathing. Categorical
variables are reported as frequency and percentage, while continuous
variables are reported with median and interquartile range. All data
analyses were performed using Stata 13.1 software.

\textbf{Results}

A total of 42 infants were enrolled (Table 1). Thirty-two (76.2\%)
infants were transferred from other medical centers. The mean
gestational age at birth was 27.1 weeks. At the time of FE, infants had
median PMA of 43.2 weeks, median chronological age of 15.1 weeks, and
mean (SD) body weight of 3.4 (0.6) kg. Of the 22/42 (52.4\%) infants who
required respiratory supports with invasive airway, 15/42 (35.7\%) had
ETs and 5/42 (11.9\%) had tracheostomy tubes; PPV with nasal prongs was
used in 16/42 (38.1\%) infants and oxygen cannula was used in 4 (9.5\%)
infants. The leading indications for FE assessment were failure to wean
PPV in 36 (85.7\%), failed ET extubation in 27 (64.3\%) and abnormal
breathing sound in 15 (35.7\%). Thirty-five (83.3\%) infants had more
than one indication.

Endoscopes used

Two thin flexible endoscopies without inner channel, Olympus LFP scope
(out diameter 1.8 mm, working length 60 cm) or Olympus LFP scope (out
diameter 2.6 mm, working length 30 cm), were used for FE-NIV procedures.
Endoscopes of appropriate size were chosen to pass and assess through
2.5 mm to 4.0 mm inner diameters of invasive airway as well as from the
nose to all approachable AE tract in infants without invasive airway.

FE revealed AE tracts pathologies in 38 (90.5\%) infants where total of
129 lesions were identified (Table 2). There included 111 airway lesions
in 35 (83.3\%) infants and 18 esophageal problems in 15 (35.7\%)
infants. Among them, 28 (66.7\%) infants had detected more than one
lesion. Of the 111 airway lesions, most frequently identified were
bronchial granulations (28, 25.2\%), TMs (18, 16.2\%), BMs (15, 13.5\%)
and subglottic stenoses (11, 9.9\%). Bronchial granulations were right
side dominant (right 21, left 10 and bilateral 7), and all at distal
bifurcations of the primary bronchi, contributing to local malacia. The
18 esophageal lesions identified comprised of 12 (66.7\%) loose of
gastroesophageal junction, 3 (16.7\%) esophageal inlet stenoses and 3
(16.7\%) mid-esophageal stenoses.

The mean (SD) duration of FE-NIV procedure for infant with invasive
airway was 102 (33) seconds, whereas for infants without airway tubing,
assessing whole three routes of AE tract was 227 (55) seconds. (Table 3)
Eight (19\%) infants had developed transient desaturation
(\textless{}85\% or less than 10\% of prior baseline level) or
bradycardia (\textless{}100 beat/min) more than than 60 seconds. They
all got recovery within 60 seconds after a brief NIV (NC-AC) maneuvers.
Durations of desaturation or bradycardia were all less than 120 seconds.
No pulmonary air-leak associated with the FE-NIV procedures was noted.
All infants successfully withstood and completed the FE-NIV procedures.

FE findings led to resultant changes in clinical management in 38/42
(90.5\%) infants (Table 4), where a total of 158 changes along with the
respective rationales was tallied. There were 64 changes of respiratory
care among 36/42 (85.7\%) infants, which consisted of titrations of PPV
(29/64, 45.3\%), shallow suctioning (17/64, 26.6\%), ET (or tracheostomy
tube) insertion depth adjustments (10/64, 15.6\%) and ET extubations
(8/64, 12.5\%). Twenty-one (21/42, 50.0\%) infants had changed 50
medications which included addition of systemic steroids (15/50,
30.0\%), addition of anti-reflux medicine (14/50, 28.0\%),
discontinuation of antibiotics (13/50, 26.0\%), and addition of
antibiotics (8/50, 16.0\%). In 18 (42.9\%) infants, 37 therapeutic
interventions were performed with the aid of FE-NIV, which included
balloon dilatations of narrow lumens (14/37, 37.8\%), laser-plasty for
stenotic lesions or granulation ablations (13/37, 35.1\%) and stents
implantation (10/37, 27.0\%) for severe (collapse more than 90\%)
tracheobronchial malacia caused difficult weaning the PPV. In these 10
stents implantations, there were 4 TM, 4 CM (2 right and 2 left) and 2
left main BM. Seven (7/42, 16.7\%) infants received surgical procedures
due to failure of medical management which included 4 tracheostomies for
severe subglottic stenosis and 3 fundoplications for severe GERD.

\textbf{Discussion}

This is the first report in literature on performing FE-NIV assessment
in the whole approachable AE tract in infants with sBPD. FE-NIV is a
practical and well-tolerated modality even in cardiopulmonary
compromised infants. In this study, all infants received complete FE
assessments, and each assessment was safely accomplished in no more than
seven minutes. Transient desaturation or bradycardia that occurred were
all resolved in less than two minutes of applying this NIV maneuvers.

BPD is a clinically challenging condition. Many AE tract pathologies
that resulted in lumen narrowing or incompetency may be frequently
undiagnosed or misdiagnosed due to poor diagnostic value of indirect
radiographic images or intolerance to direct FE procedures without
appropriate support. Airway tissue of premature infants are particularly
vulnerable be injury as they are fragile and
compliant.\textsuperscript{19,20} Since birth, their AE tracts bore
frequent invasive processes such as intubations, suctioning, infections
and barotrauma of prolonged PPV during their complicated and lengthy
hospitalizations. These iatrogenic damages might result in tissue
fibrosis, lumen stenosis and structural
weakness.\textsuperscript{21-23}In addition, infants with sBPD also
encounter recurrent complications such as sepsis, cyanotic episodes,
apnea and difficulty weaning. Therefore, they are best assessed and
managed by a multidisciplinary team specializing in comprehensive care
of the complex disorders.

For infants with invasive airways (ET or tracheostomy tube), we started
the FE assessment through the artificial lumens evaluating
tissue-condition around the tube's tip, where the most iatrogenic trauma
rise. By manipulating FE and invasive airway, we imitate the dynamic ET
tip motion and the suction catheter against the mucosal wall of
tracheobronchial lumens in vivo. The ET or FE tips might embed into a
granuloma, against the main carina, or even block a bronchial branch.
Additionally, the tip of suction catheter might repeatedly striking
against the bifurcations of a branch and resulted in granulation
formations. All of these causes of traumatic striking might be ignored
after extubation. For infants without ET or after extubation,
comprehensive assessment with FE-NIV began from the nostrils down to the
all-approachable bronchi, esophagus, and stomach were performed with
increased focus around the hypopharynx, larynx and supra-stomy region
where majority of ET, tracheostomy tube, suctioning and feeding tube
related injuries might exist.\textsuperscript{24-26} Kurachek, et
al.\textsuperscript{22} reported that that upper airway lesions like
laryngomalacia, subglottic stenosis, TM, BM or tracheobronchial malacia
are the leading causes of extubation failure in pediatric patients. In
this study, majority of infants with sBPD (38/42, 90.5\%) had AE
pathologies detected by FE-NIV. These findings highlight the importance
of performing precise AE tracts evaluation.

Failure of extubation or weaning respiratory support in patients with
sBPD due to pathologies involving AE tract have been well reported in
the literature.\textsuperscript{23,27-29} In our study, positive rate of
90.5\% (38/42) was higher than rate of 74.0\% (20/27) from previous
study by Hysinger\textsuperscript{4} in which only airway pathologies
were identified. Utilizing the novel FE-NIV approach, we were safely
take time and able to detailedly examined AE regions including
pharyngolarynx, upper trachea and esophagus, and thus, yielded more
pathologic findings. These findings allowed us to further adjust and
formulate appropriate and individualized treatment strategies for
lesions encompassing not only the airway tracts, but also the esophageal
portions.

Consequent changes of respiratory cares and medication management were
adjustment. For symptomatic or refractory airway lesions such as severe
granulations, stenosis and malacia, we were capable of providing
effective therapeutic interventions through the FE-NIV
procedure,\textsuperscript{15,30} including laser ablation for
granulations and balloon dilatation for lumen stenoses. Additionally, in
selected infants of severe airway malacia with frequent life-threatening
episodes and failed to achieve satisfactory response to such management,
we were able to performed stent placements\textsuperscript{16,30} over
the affected sites with aid of FE-NIV, thus forestalling the need of
more invasive surgical approach. In this study, surgeries of
tracheostomy and gastric fundoplication were reserved for severe,
refractory subglottic stenosis and GERD, respectively.

Performing FE-NIV approach for assessment of sBPD infants provides
several advantages. First, it is a simple and practical skill that
obviates the need for artificial airway devices such as face-mask,
ventilation bag, laryngeal airway mask, ET, ventilator, or equipment as
HFNC that is cost-effective and applicable in resource-limited
situations. Compare to the HFNC, this NIV may be better in less oxygen
flow needed, interface near the larynx, and provide controllable PPV for
effects of splinting airway and oxygenation. Second, in the
``PhO\textsubscript{2}'', the ventilation interface locates near the
larynx which has less death space and it functioning likes the
physiology of ``apneic oxygenation''\textsuperscript{31,32} can prolong
duration of safe oxygen saturation. Third, due to less airway devices
used, workspace for FE handling and manipulation is less occluded,
allowing for smoother procedure, careful measurement and yield more
comprehensive pathologies. Fourth, it can provide direct and dynamic
visual evidence-base information that is valuable to formulate clinical
decisions for individualized management. Fifth, addition of SPI and AC,
it can safely support the PPV, provide a less hurried approach, improve
the FE assessment as well as the more invasive therapeutic procedures,
even in cardiopulmonary compromised infants.\textsuperscript{15-17,29}

There are several limitations presented in this study. 1) Due to
retrospective nature, it was difficult to clarify the complex factors
contributed to these pathologies, especially for infants who were
transferred to our hospital relatively late in their clinical courses.
2) No bronchoalveolar lavage was performed during FE that was due to it
could easily be achieved by direct suction from invasive airway and also
concerned about tracheobronchial colonization in these infants. As
result, we preferred using FE with no inner channel. 3) The sample size
was small and the FE-NIV used in the study was single-center based.
Future multicenter studies of the FE-NIV assessment in whole AE tract
may be needed to more clarify the issues.

\textbf{Conclusion}

This FE-NIV is a simple, safe and valuable procedure for obtaining
direct visuals and complete diagnosis of AE lesions, which could assist
clinicians in formulating appropriate clinical decisions to guide
individualized management in infants with sBPD.

\textbf{Conflict of Interests}

All authors declare that there is no conflict of interests regarding this
paper.

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