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\begin{document}

\title{Bronchoscopic Features and Correlative Factor Analysis of Severe
Mycoplasma pneumoniae Pneumonia in Children.}



\author[1]{haiming yang}%
\author[1]{Gan Li}%
\author[2]{Xicheng Liu}%
\affil[1]{Beijing Children's Hospital}%
\affil[2]{Beijing Children's Hospital Capital Medical University}%


\vspace{-1em}



  
  \date{May 16, 2024}


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\selectlanguage{english}
\begin{abstract}
Objectives: We aimed to determine the bronchoscopic features of children
with severe Mycoplasma pneumoniae pneumonia (SMPP), and correlation with
obliterative bronchitis (OB), so as to help early clinical evaluation
and treatment of pediatric SMPP. Methods: 213 pediatric SMPP cases
admitted to Beijing Children's Hospital were included. Medical records
and bronchoscopic manifestations at different SMPP stages were
retrospectively analyzed . Results: Of 213 acute-stage pediatric SMPP
patients, bronchoscopy revealed 22 cases (10.3\%) with subacute-stage or
recovery-stage OB, for an OB incidence rate in cases with mucous embolus
of 48.8\% (22/47), a significantly higher rate than the rate without
mucous embolus (0/166, 0\%) (P \textless{} 0.001). Notably, the OB
incidence rate for children undergoing bronchoscopy within 10 days
(9/142, 6.3\%) of SMPP onset was significantly lower than in children
undergoing bronchoscopy 10 days post-disease onset (13/71, 76.5\%) (P
\textless{} 0.007). Conclusions: In pediatric SMPP patients, airway
mucus and debris from epithelial necrosis and exfoliation can block
airway subbranches, readily leading to OB.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

\emph{Mycoplasma pneumoniae}pneumonia (MPP) is one of the most common
types of community-acquired pneumonia (CAP) in
children.\textsuperscript{1} Macrolide antibiotics are effective
treatments for most patients, but in some cases MPP may progress to
severe MPP (SMPP). SMPP patients exhibit poor responses to single
macrolide antibiotics and progression of disease that is accompanied by
persistent high fever, aggravation of pulmonary lesions, and additional
complications, such as necrotizing pneumonia, atelectasis,
bronchiectasis, obliterative bronchiolitis (OB), and other disorders.
SMPP complications can lead to repeated infections and decreased quality
of life for afflicted children.\textsuperscript{2,3}

The pathogenesis of SMPP likely involves many processes, such as
excessive immune inflammatory reactions, mixed infections, and so on.
Therefore, the abovementioned factors should be considered during SMPP
treatment to reduce the development of pulmonary sequelae. Notably,
using bronchoscopy we have found that MPP is associated with specific
manifestations such as airway mucus blockage and mucosal necrosis as
main findings that cannot be completely eliminated by conservative
treatments such as antibiotics and glucocorticoids. Indeed, airway
blockage is of particular concern in that it can occur within a short
period of time and progress to permanent atelectasis. Therefore,
avoidance of OB should be an early treatment priority for practitioners
caring for pediatric MPP patients in China, especially in the northern
region.\textsuperscript{4} Consequently, a better understanding of the
effects of early abnormal dynamic inflamed airway changes on later
incidence of airway occlusions and their implications for MMP treatment
have not yet been reported. Such information may be acquired via
bronchoscopy, which can facilitate SMPP diagnosis during acute-phase MMP
by providing bronchial lavage fluid for pathogen detection and
information pertaining to microscopic disease manifestations. Also,
bronchoscopy can reveal complete membranous obstructions within
subsegmental bronchi of OB cases.

In this retrospective study, we analyzed bronchoscopic findings of
pediatric SMPP patients admitted to Beijing Children's Hospital
affiliated with Capital Medical University from October 2017 to January
2019 to reveal correlations between bronchoscopically determined disease
manifestations and SMPP prognosis.

\textbf{METHODS}

\emph{Subjects}

This study was a retrospective analysis of pediatric patients afflicted
with SMPP and admitted to the hospital from June 2017 to January 2019.
Diagnostic criteria of MPP were as follows: (1) fever, cough, and other
clinical manifestations; (2) chest image findings indicative of
pneumonia; (3) MPP-specific IgM antibody titer persisting at a level [?]
1:320, or an antibody level that increased 4-fold during convalescent
and acute SMPP phases (passive agglutination method, Fujirebio Inc.,
Japan). Based on MPP diagnosis combined with the latest diagnostic
criteria for severe CAP in China, any one of the following criteria was
used as a reference for the diagnosis of
SMPP:\textsuperscript{5,6}obvious shortness of breath or tachycardia
(criteria: 1-5 years old, RR [?] 40 times/min; \textgreater{}5 years old,
RR [?] 30 times/min, respectively); hypoxemia during inhalation and pulse
oximetry-based oxygen saturation (SaO\textsubscript{2}) less than 0.93;
chest images demonstrating multi-lobe or segment involvement or
pulmonary area involvement of greater than 2/3 of the total lung area;
pleural effusion, atelectasis, pulmonary necrosis, pulmonary abscess,
and other pulmonary complications; complications associated with severe
damage of other systems, such as central nervous system infection, heart
failure, myocarditis, gastrointestinal hemorrhage, obvious
electrolyte/acid-base balance disorder, etc. Exclusion criteria included
previous congenital or secondary immunosuppression or defect, chronic
pulmonary disease, kidney or cardiovascular disease, and connective
tissue disorders, etc. Patients were also excluded if they were infected
with other pathogens within 7 days post-admission or did not receive
bronchoscopy at admission. All recruited children had received treatment
with macrolide antibiotics for one week without noticeable improvement.

\emph{Bronchoscopy}

Bronchoscopy was performed under the following conditions: decreased
respiratory sounds corresponding to the lesion site during auscultation;
ineffective anti-infection treatment; chest image showing large area of
pulmonary consolidation. Bronchoscopic reexamination was conducted when
chest imaging showed poor absorption of lung lesions and the airway
still harbored a mucous embolus one week after bronchoscopy had been
conducted in spite of systemic hormone and anti-MP treatment.

Bronchoscopic procedures were as follows: for each patient, the nasal
cavity and pharynx were locally anesthetized with 1\% lidocaine prior to
the procedure. After sedation via intravenous injection of 0.1-0.3 ml/kg
midazolam, bronchoscopy was performed using either an Olympus BFXP-260F
model (outer diameter 2.8 mm) or Olympus BF P-260F model (outer diameter
4.0 mm) bronchoscope via entry through the nostril. Changes in mucosa of
the nasal cavity, pharynx, trachea, bronchus, and subsegmental mucosa
were observed in turn. If the mesh foreign body basket was blocked by
mucous plugs or the cell brush removed mucus plugs from the airway, deep
subsegmental bronchi lumens were infused with not more than 5 ml/kg
0.9\% sodium chloride according to patient body weight. Routine
examination of lavage fluid was conducted to determine etiology.

The study was approved by the ethics committee of Beijing Children's
Hospital. All parents or legal guardians provided written informed
consent before conducting the study and any study-related procedures.

\emph{Data Collection}

Bronchoscopic manifestations, time between disease onset and
bronchoscopy, lung images, serum C-reactive protein (CRP), and body
temperature changes were analyzed retrospectively. The following data
were assessed: bronchoscopic manifestations of pediatric SMPP patients
with different imaging findings; lavage fluid pathogen detection; time
of body temperature recovery to normal, and total fever course after
bronchoscopy; OB incidence, time to OB onset, and disease
characteristics; pulmonary imaging results, including lesion site, type,
imaging findings, and therapeutic outcome; duration of fever during
disease course and after bronchoscopy; inflammatory indexes, such as
routine blood and CRP test results.

\emph{Statistical Analysis}

SPSS statistics Version 22.0 (International Business Machines (IBM)
Corporation) was employed for data analysis. Enumeration data were
expressed as percentages and the \selectlanguage{greek}χ\selectlanguage{english}2 test was used for comparisons
between groups. Measurement data conforming to the normal distribution
were expressed as the mean \selectlanguage{ngerman}± standard deviation (SD) and the t-test was
used to make comparisons between two groups. The median {[}interquartile
range (IQR) M(P\textsubscript{25}-P\textsubscript{75}){]} was used for
measurements of data not conforming to the normal distribution and the
rank-sum test was used to make comparisons between two groups. Count
data were expressed by rate or constituent ratio and chi-squared testing
was performed. A value of P \textless{} 0.05 was considered
statistically significant.

\textbf{RESULTS}

\emph{Study Population}

A total of 248 cases were diagnosed with SMPP, of which 213 cases met
the enrollment criteria. The average time period that elapsed from
disease onset to first bronchoscopy was 8.9 ± 2.4 days, with the average
number of prior bronchoscopies found to be 2.2 ± 1.8. Of the enrolled
cases, 142 cases (142/213, 66.7\%) had their first bronchoscopy within
10 days post-disease onset, while 71 cases (71/213, 33.3\%) had their
first bronchoscopy 10 days post-onset of disease. 183 cases (183/213,
85.9\%) underwent bronchoscopy no more than twice, while 30 cases
(30/213, 14.0\%) underwent bronchoscopy at least three times (Table 1).

\emph{Clinical and Bronchoscopic Manifestations}

In this study, disease course was assessed based on clinical
manifestations, lung imaging, and bronchoscopic findings then was
classified into three disease course categories: acute-stage,
subacute-stage, and recovery-stage.

Symptoms during acute-stage SMPP included fever, elevated CRP, and large
areas of consolidation detected via lung imaging. Generally, detection
of bronchial mucosal congestion with or without airway mucosal
follicular hyperplasia and bronchial secretions increased with use of
bronchoscopy. Symptoms of subacute-stage SMPP were characterized by
decreased or normal fever peak, improved signs as assessed via lung
imaging, increased blood CRP, and decreased bronchial secretions and
airway blockages accompanied by mucous membrane necrosis and exfoliation
found via bronchoscopy. Symptoms of recovery-stage SMPP included normal
body temperature, normal blood CRP, and either improved findings via
lung imaging or atelectasis.

Bronchoscopic manifestations of acute-stage SMPP: all cases exhibited
different degrees of congestion and roughness of tracheal and bronchial
mucosa, mucosal longitudinal fold changes, and mucinous secretion.
During the first bronchoscopy, follicular hyperplasia of airway mucosa
was found in 162 cases (162/213, 76\%), with lung lesions located in
grade I and grade II trachea. Erosion of airway mucosa was found in 105
cases (49.2\%), with lesions located in grade III or lower grade
bronchi. Mucous plug blockages involving grade III or lower bronchi were
found in 47 cases (47/213, 22.0\%). The mean disappearance time of
mucous plugs was 15 ± 1.7 days. The mean number of previous
bronchoscopies was 2.6 ± 3.5. Of cases with mucous plugs, 8 cases
(8/213, 3.8\%) had severe mucous plug obstruction (with tree-like
bronchial-shaped changes). Locations of lesions were as follows: lesions
of 11 cases (11/213, 10.5\%) were in the left upper lung, of 15 cases
were in the left lingual lobe (15/213, 14.3\%), of 48 cases were in the
left lower basal segment (48/213, 45.7\%), of 13 cases (13/213, 12.4\%)
were in the right upper lobe, of 10 cases (10/213, 9.5\%) were in the
right middle lobe, of 64 cases (64/213, 60.9\%) were in the right lower
basal segment, of 63 cases (63/213, 60\%) were in one lobe, of 32 cases
(32/213, 30.5\%) were in two lobes, of 7 cases (7/213, 6.7\%) were in
three lobes, of 3 cases (3/213, 2.8\%) were in four lobes; no cases
involved five lobes.

Bronchoscopic manifestations in subacute and recovery stages: 22 cases
(22/213, 10.3\%) had OB, including 13 males (13/22, 59\%) and 9 females
(9/22, 41\%). The median time to diagnosis of Sub-bronchial stenosis was
15 days {[}IQR 12-18{]}. The initial obstruction was a thin film that
was easily broken with biopsy forceps in order to reopen the airway.
With time, the untreated occluded airway section gradually thickened and
the center became concave and became associated with a peripheral radial
hyperplasia-like obstruction. Proximal tracheal examination revealed the
presence of fishbone-like bronchiectases that were difficult to reopen
using biopsy forceps (Figures 1 and 2).

\emph{Analysis of Factors Associated with SMPP Progression to OB}

Of 47 (46.8\%) pediatric SMPP patients with mucous emboli, 22 patients
developed OB and no OB was found in children without mucous emboli;
thus, OB incidence in children with mucous emboli was significantly
higher than in children without mucous emboli (P \textless{} 0.001). All
8 cases (100\%) with plastic bronchitis determined via bronchoscopy
exhibited different degrees of OB. During the convalescent stage, OB
occurred in 4 of 183 cases (2.2\%) reporting two or fewer prior
bronchoscopies and 18 of 30 cases (60\%) with at least 3 prior
bronchoscopies. The incidence of OB in children with two or fewer
bronchoscopies was significantly lower than OB incidence in children
with at least three prior bronchoscopies (P \textless{} 0.001).
Importantly, of 142 children (6.3\%) who had the first bronchoscopy
within 10 days of disease onset, 9 developed OB (6.3\%); of 71 children
who had their first bronchoscopy on or after 10 days of disease onset,
13 (76.5\%) developed OB. Therefore, OB incidence of children undergoing
bronchoscopy within 10 days of disease onset was significantly lower
than that of children undergoing bronchoscopy at or after 10 days
post-disease onset (P \textless{} 0.007). Moreover, the average chest CT
number for children with acute stage obstructive bronchitis was 26 u,
while the average CT number for children without OB was 19 u. Thus,
chest CT values of children with OB were significantly higher than those
of children without OB, with the difference between groups reaching
statistical significance (P \textless{} 0.05). Notably, OB was found in
all 6 cases afflicted with necrotizing pneumonia (100\%), as detected
via pulmonary imaging (Table 2, Figure 3).

\emph{Adverse Events}

No massive hemorrhage occurred. However, during acute-stage SMPP some
bronchoalveolar lavage or cell brush interventions caused a small amount
of bleeding. In such cases, a local application of 1:10000-diluted
adrenaline may help. No case of pneumothorax was detected.

\textbf{Discussion}

Children afflicted with SMPP have severe clinical symptoms and more
complications than those with MPP, including necrotizing pneumonia,
atelectasis, bronchiectasis, OB, and permanent airway structural damage.
As a result, lung function declines and repeated infections can impact
quality of life for these patients. According to previous studies, main
clinical manifestations of pediatric SMPP include continuous high fever
and the presence of large areas of lung consolidation detected via
pulmonary imaging. These findings reflect an overactive immune response
that often requires hormone therapy for suppression of harmful
inflammatory processes.\textsuperscript{7-9}

The clinicalClinical manifestations of MPP in China differ from those
reported in other countries, with symptoms more serious in China,
especially in northern areas.\textsuperscript{4} In recent years, the
widespread application of pediatric bronchoscopy for SMPP diagnosis and
treatment has led to great progress in treating this disorder in China.
Although some practitioners doubt the value of bronchoscopic findings
for MPP prognosis, the value of bronchoscopy has been demonstrated for
pediatric SMPP prognosis in China. In this study, congestion and
swelling of airway mucosa were obvious in acute-stage cases examined via
bronchoscopy, with some of these findings accompanied by follicular
hyperplasia, a relatively specific MPP-associated manifestation.
Meanwhile, during bronchoscopy bronchoalveolar lavage fluid is readily
collected for use in MPP pathogen detection as a direct and effective
method for achieving differential MPP diagnosis and treatment.
Importantly, acute-stage SMMP mucous plug obstructions should be cleared
bronchoscopically in a timely manner in order to maintain unobstructed
airway subbranches and subsequently control infection. In subacute-stage
SMMP, bronchoscopy can be used to monitor recovery from airway
inflammation and detect OB sequelae for use in guiding treatment and
respiratory rehabilitation planning. Therefore, bronchoscopic
examination and intervention can benefit children with SMMP, with no
significant adverse effects of bronchoscopy found in this study.

OB, a type of chronic airflow obstruction syndrome, mainly involves
small and medium bronchi and is associated with proliferation of fibrous
tissue. The main manifestations of OB are atelectasis and lobar
collapse. Under bronchoscopic examination, the distal obliterans of some
subsegmental and subsubsegmental bronchi of OB patients is accompanied
by atrophy of proximal mucosa, appearance of obvious cartilage rings,
and lumen expansion. OB often occurs secondary to severe pneumonia and
has gradually gained recognition as a common SMPP-associated
sequela,\textsuperscript{10} although few studies in China or abroad
have described OB caused by \emph{M. pneumoniae} infection. With
increasing research attention paid to SMPP airway damage, OB detection
rates have significantly increased and highlight OB as an urgent
clinical problem stemming from processes underlying SMPP development.
Meanwhile, studies have shown that MP infection can result in cellular
and humoral immune dysfunction and disturbances of cytokine networks.
Moreover, an excessive inflammatory reaction causes airway mucosal
epithelial damage followed by airway subbranch injury that leads to scar
contracture and occlusion. In this study, it was observed that OB caused
by SMPP mainly involved grade III bronchi or below. The OB developmental
process could be outlined as follows: in acute-stage disease, diseased
sub-bronchi begin to erode then mucous plugs develop and blockages form.
Next, necrotic epithelium detaches and blocks the airway in the subacute
stage. Afterwards, subsegmental bronchi gradually became narrower,
leading to poor ventilation, insufficient local blood supply surrounding
lesions, then gradual formation of obliterans. The obliterans formation
process supports the conclusion that obliterans are caused by airway
injury. Meanwhile, initial obliterans lesions first appear as a thin
film that is easily reopened using biopsy forceps. Next, the occluded
part gradually thickens to form a barrier that biopsy forceps cannot
reopen in most cases. It has been suggested that it may be possible to
reopen airway branches after choosing the appropriate timing for
bronchoscopic intervention, with further study needed to optimize
interventional timing for improved treatment outcomes.

In this study, the timing of bronchoalveolar lavage was also
investigated to detect correlations with OB incidence during late-stage
SMPP. Specifically, the incidence of OB in pediatric patients who
received first bronchoalveolar lavage at 10 days post-SMPP onset was
significantly higher than that of children receiving their first
bronchoscopies within 10 days post-disease onset. It has been suggested
that for pediatric patients with persistent fever and large lung
consolidations, atelectasis, and other pulmonary pathological changes
detected via imaging within 10 days of onset, timely bronchoalveolar
lavage is recommended to avoid complications such as OB.

The main components of bronchial mucous plugs include a mixture of mucin
and cellular debris combined with a large number of infiltrating
inflammatory cells that make this mixture extremely viscous. At present,
it is widely recognized that hyperimmune inflammation is one of the main
pathogenic mechanisms underlying SMPP.\textsuperscript{3,11} MP
infection tends to lead to mucosal necrosis and mucus hypersecretion via
a mechanism that may involve direct damage and release of
infection-triggered toxic metabolites that ultimately damage bronchial
epithelial cells and cilia. Such pathological damage may further impair
mucociliary system function and weaken ciliary discharge capacity and
clearance of secretions. Afterwards, tethered secretions that form
within the local airway can trigger airway obstruction, with local
obstruction of the proximal bronchus and various sizes of mucous plugs
occurring within deep subsegmental bronchi in some serious cases. This
study demonstrated that pediatric SMMP patients who also developed OB
during late-stage disease exhibited different degrees of mucous plug
development during acute-stage SMPP that were detected via bronchoscopy.
Therefore, for patients with mixed lesions that are associated mainly
with mucous plugs, mucus necrosis, and particularly with successive
mucus plug development detected upon bronchoscopic reexamination,
localization of mucous plugs should be done as early as possible in
conjunction with administration of systemic treatment. Moreover, regular
bronchoalveolar lavage treatment would facilitate the timely removal of
mucous plugs in order to improve ventilation and secretion clearance at
lesion sites and promote inflammatory absorption.

This study demonstrated that the density of large consolidation areas
was significantly increased during acute-stage SMPP, suggesting that
subbranches can be severely blocked by mucous embolisms. Thus,
bronchoscopy should be performed as soon as possible to remove airway
secretions that in such cases consist of thick viscous mucus that is
difficult to clear away. For conducting a first bronchoscopic
examination of patients with this type of lesion, a bronchoscope with a
larger diameter (such as 4.0 mm) is recommended; because the diameter of
the suction duct is large, it can loosen and brush mucous plugs to the
depth of subsegmental bronchi and can effectively remove mucous plugs
from deeper airways with the help of a cell brush. Due to acute-stage
mucosal damage and congestion, adrenaline can be applied locally to
shrink blood vessels while plugs are slowly and gently brushed to
minimize bleeding during plug removal. During late-stage SMPP recovery
characterized by improved lung imaging findings, the 2.8-mm diameter
bronchoscope could be selected for subsequent inspection and clearance
of deep subsegmental bronchial mucous plugs.

Due to the risk of pneumothorax that may occur during bronchoscopic
examination and treatment of necrotic pediatric SMPP, the use of
bronchoscopy for such cases is still controversial at present. However,
it is worth noting that of 6 patients with late-stage necrotic pneumonia
receiving treatment in this study, all of these patients developed OB
even though they had different degrees of bronchoscopically detected
airway blockage due to mucous plugs and mucinous necrosis. Notably, no
pneumothorax occurred as a result of bronchoscopic treatment.
Nevertheless, owing to the small sample size of this study, it is
impossible to judge the advantages and disadvantages of bronchoscopy for
necrotic SMPP based solely on results of this study.

In summary, pediatric SMPP patients exhibit certain characteristics
during different disease stages that can facilitate diagnosis. However,
airway mucus and mucosal epithelial necrosis and detachment could lead
to clogging of subbranches and subsequent OB. Thus, it is recommended
that pediatric SMPP patients with mucous plugs undergo timely
bronchoscopy in addition to customary antibiotic treatment. Because this
study did not comprehensively summarize and analyze factors associated
with OB in pediatric SMPP patients, predictive factors predisposing
patients to OB development were not definitively identified. Therefore,
collection of additional clinical data is needed to further evaluate
possible predictors of later OB occurrence that would be used to inform
future clinical practice.

\selectlanguage{english}\textbf{Acknowledgements:} We thank the children and families who
graciously consented to participate in the bronchoscopy of SMPP children
in this study.

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\end{enumerate}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Age(years old)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Male/Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Female /Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Pulmonary consolidation} \textbf{cases/Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Atelectasis} \textbf{cases/Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Pulmonary necrosis(cases)/Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Extrapulmonary complications(cases)/Total cases(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Average fever time (days)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Average postoperative fever time (days)}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
4.2 \selectlanguage{ngerman}± 2.6\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
114/213(53.5)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
99/213(46.4)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
213/213(100)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
189/213(88.7)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6/213(2.8)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
192/213(90.1)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.8\selectlanguage{ngerman}±1.2\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
1.8\selectlanguage{ngerman}±4.4\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{Table 2: \emph{Main factors of influencing obliterative
bronchiolitis: comparison between children with and without obliterans}}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
& \textbf{Time of first bronchoscopy since the onset of the disease} &
\textbf{Time of first bronchoscopy since the onset of the disease} &
\textbf{Times of bronchoscopy} & \textbf{Times of bronchoscopy} &
\textbf{Mucus embolus} & \textbf{Mucus embolus} & \textbf{Tree-like
bronchial shaped changes} & \textbf{Tree-like bronchial shaped changes}
& \textbf{Necrotizing pneumonia} & \textbf{Necrotizing
pneumonia}\tabularnewline
& Within 10 days & After 10 days & [?]twice & [?] three times & Yes & No &
Yes & No & Yes & No\tabularnewline
\textbf{Cases} & 142 & 71 & 183 & 30 & 47 & 166 & 8 & 205 & 6 &
207\tabularnewline
\textbf{Obliterans cases} & 9 & 13 & 4 & 18 & 22 & 0 & 8 & 14 & 6 &
16\tabularnewline
\textbf{P value} & P<0.007 & P<0.007 & P<0.001 & P<0.001 & P<0.001
& P<0.001 & P<0.001 & P<0.001 & P<0.001 & P<0.001\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figures and Legends}

\textbf{Figure 1: \emph{Chest X-ray and high-resolution CT showed large
consolidation shadow in the left lower lung(A,B,C).Obvious hyperemia of
bronchial mucosa and nodular protrusion on the surface of mucosa (D).
Longitudinal fold change of subbronchiolar mucosa and mucus plug
obstruction in the lesion site of bronchial subbranch (E).The
subbronchiolar mucosa looked pale, and necrotic detachment of bronchial
epithelial mucosa blocked lumen opening(F).The subbronchiolar mucosa
were pale in color and occluded with concave center and peripheral
radial hyperplasia in the occluded part(G,H). Plastic mucus plug taken
by cell brush under bronchoscope(I).}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 2: \emph{Chest high-resolution CT showed atelectasis in
the left lower lung three weeks after the onset of the disease(A). The
color of subbronchiolar mucosa was pale and the lumen was occluded(B).
Biopsy forceps were used to recanalize the subbranch occlusion under
bronchoscope(C) and the recanalized airway subbranch(D).Chest
high-resolution CT scan showed that atelectasis in the left lower lung
got better one month after bronchoscopy(E).}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 3: \emph{Chest X-ray and high-resolution CT discovered
large consolidation shadow with liquefactive necrosis and cavity in
right lung (A,B,C). Extensive occlusion in left lower pulmonary bronchus
under bronchoscope(D).}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

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

