\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Bilateral refractory pneumothorax treated by pleurodesis and bronchial
occlusion in a COVID-19 patient}



\author[1]{Satoshi Tanaka}%
\author[1]{Yoshihiro Takayama}%
\author[1]{Riiko Kitou}%
\author[1]{Ryo Asakawa}%
\author[1]{Satoshi Tobita}%
\author[1]{Akihiro Ike}%
\author[1]{Masahiro Kawada}%
\author[1]{Suguru Yamamoto}%
\author[1]{Kiyonobu Ueno}%
\affil[1]{Osaka General Medical Center}%


\vspace{-1em}



  
  \date{June 02, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Coronavirus disease 2019 (COVID-19) can cause various complications.
Pneumothorax secondary to COVID-19 is relatively uncommon and bilateral
pneumothorax is even more so. In patients with poor general health to
undergo surgery for pneumothorax, internal treatments are essential to
relieving refractory pneumothorax.%
\end{abstract}%



\sloppy


\textbf{CASE REPORT}

\textbf{Bilateral refractory pneumothorax treated by pleurodesis and
bronchial occlusion in a COVID-19 patient}

Satoshi Tanaka, MD\textsuperscript{1}; Yoshihiro Takayama,
MD\textsuperscript{1}; Riiko Kitou, MD\textsuperscript{1}; Ryo Asakawa,
MD\textsuperscript{1}; Satoshi Tobita, MD\textsuperscript{1}; Akihiro
Ike\textsuperscript{2}; Masahiro Kawada, MD \textsuperscript{3}

Suguru Yamamoto, MD, PhD\textsuperscript{1}; Kiyonobu Ueno, MD,
PhD\textsuperscript{1}

\textsuperscript{1}Department of Respiratory Medicine, Osaka General
Medical Center, Osaka, Japan

\textsuperscript{2}Department of Thoracic surgery, Osaka General Medical
Center, Osaka, Japan

\textsuperscript{3}From the Division of Trauma and Surgical Critical
Care, Osaka General Medical Center

\textbf{ABSTRUCT}

\textbf{Coronavirus disease 2019 (COVID-19) has become a worldwide
outbreak, and it can cause various complications. However, pneumothorax
secondary to COVID-19 is relatively uncommon. We herein report a
60-year-old man with bilateral refractory pneumothorax with severe
COVID-19. In patients with poor general health to undergo surgery for
pneumothorax post COVID-19, internal treatments such as chest drainage,
bronchial occlusion and pleurodesis are essential to relieving
refractory pneumothorax. It also indicates that autologous blood patch
pleurodesis is a useful method in terms of efficacy and side effects.}

\textbf{1 INTRODUCTION}

The outbreak of coronavirus disease 2019 (COVID-19) infection has been
widespread all over the world. COVID-19 infection can cause various
complications and pneumothorax secondary to COVID-19 is relatively rare.
Pneumothorax as a complication of COVID-19 infection occurs in 1\% of
hospitalized COVID-19 patients\textsuperscript{1} and 2\% of COVID-19
patients in intensive care unit\textsuperscript{2}. Simultaneous
bilateral spontaneous pneumothorax is an extremely rare condition that
is found in only 1\% of all patients with spontaneous
pneumothorax\textsuperscript{3}. There have been few reports of
bilateral pneumothorax due to COVID-19. There is no treatment strategy
for secondary spontaneous pneumothorax due to COVID-19. In patients with
poor general condition and who are not fit for surgery, refractory
pneumothorax must be cured by internal therapies (chest drainage,
bronchial occlusion and pleurodesis, and so on). There are various drugs
in pleurodesis and autologous blood is a better adhesion in terms of
efficacy and side effects. We herein report a rare case of a severe
COVID-19 patient with bilateral refractory pneumothorax treated by
combining internal treatments.

\textbf{2 CASE HISTORY}

A 60-year-old Japanese man with no medical, family, or smoking history
was diagnosed with coronavirus disease 2019 (COVID-19). Two weeks later,
he was bought to our hospital in an ambulance because of high fever and
dyspnea. He required oxygen supplementation at 15 L/min via an oxygen
mask with an oxygen reservoir and he was immediately intubated. Computed
tomography (CT) revealed bilateral diffuse infiltrations (Fig.1A, 1B)
and he was diagnosed as having bacterial and secondary organizing
pneumonia following COVID-19 infection. He was treated with antibiotics,
methylprednisolone, and heparin sodium. His respiratory condition
improved gradually, and mechanical ventilation was discontinued on day
15. He complained of right chest pain on day 22, and CT revealed
right-sided pneumothorax. A chest drain was inserted immediately, which
was removed on day 29 after pleurodesis with minocycline (MINO) 200 mg
and OK-432 5KE. However, the right-sided pneumothorax recurred on day
50, and a left-sided pneumothorax appeared on day 56. Chest drainage was
performed on both sides, and an additional drain was placed on the right
side (Fig. 1C). He underwent pleurodesis on both sides (right side:
twice with MINO 200 mg and OK-432 5KE and twice with 100mL of autologous
blood, left side: twice with 100mL of autologous blood); however, the
air leak persisted. There were more leaks on the left side than on the
right side; therefore, we performed a bronchial occlusion procedure
using Endobronchial Watanabe
Spigots\selectlanguage{ngerman}\textsuperscript{®}(EWS\textsuperscript{®}; Novatech, La Ciotat,
France) for the left-sided pneumothorax on day 68. We inserted a 6-mm
EWS\textsuperscript{®} into B8b\selectlanguage{english}i and a 7-mm EWS\textsuperscript{(r)} into
B8b\selectlanguage{english}ii on the left (Fig. 1D). Bronchial occlusion procedure was performed
using flexible bronchoscopes (1T290 and P290, Olympus, Tokyo, Japan) and
curette (CC-4CR-1, Olympus, Tokyo, Japan). The right lung expanded fully
after bronchial occlusion and pleurodesis with 100mL of autologous blood
added on both sides, performed once on the right side and twice on the
left side. Thereafter the air leaks on both the sides stopped, and
bilateral pneumothorax improved. The right drain was removed on day 73
and the left drain on day 75. Thereafter, there was no recurrence of
pneumothorax and he was discharged on day 202 after rehabilitation for
ICU-acquired weakness.

\textbf{3 DISCUSSION}

Bilateral pneumothorax due to COVID-19 has not been widely reported in
the literature so far. The pathophysiology for the development of
pneumothorax in patients with COVID-19 is unclear; however, cystic and
fibrotic structural changes caused by COVID-19 may be
related\textsuperscript{4}. In addition to this, treatment with positive
pressure by non-invasive or mechanical ventilation in patients with
severe COVID-19 infection may contribute to the development of
pneumothorax\textsuperscript{5}. Systemic corticosteroids exhibit
anti-inflammatory and anti-fibrotic effects in patients with severe
COVID-19 infection. However, corticosteroid therapy may also cause a
delay in the wound healing process of pneumothorax\textsuperscript{6}.
There is no established treatment strategy for secondary spontaneous
pneumothorax due to COVID-19. Surgical intervention presents a better
outcome than tube thoracostomy in simultaneous bilateral primary
spontaneous pneumothorax\textsuperscript{7}. However, in some patients
surgical intervention for pneumothorax may pose high risk from the
perspective of general and respiratory condition. In patients with poor
general condition and who are not fit for surgery, refractory
pneumothorax must be cured by other internal therapies. Internal
treatments for pneumothorax include procedures such as chest drainage,
pleurodesis, endobronchial approach\textsuperscript{8}. In some cases,
it is important to combine multiple methods. We decided that our
patient's general condition was not good enough to operate. Thus, the
combination bronchial occlusion and pleurodesis relieved the patient's
bilateral refractory pneumothorax. Bronchial occlusion using an
EWS\textsuperscript{(r)} is one of the most effective and minimally
invasive treatments for secondary refractory pneumothorax, postoperative
pulmonary fistula, fistulous empyema, and bronchial fistula in patients
with poor general condition. Bronchial occlusion alone or in combination
with pleurodesis for secondary refractory pneumothorax, postoperative
pulmonary fistula, or fistulous empyema enabled drain removal in 57.1\%
to 86.0\% of patients\textsuperscript{9-11}.

Mitsuyama et al. reported that autologous blood patch pleurodesis may be
a treatment option for recurrent and refractory pneumothorax secondary
to COVID-19\textsuperscript{12}. In our case, pleurodesis with MINO and
OK-432 was ineffective, whereas the one with autologous blood was
effective. Pleurodesis with autologous blood has fewer side effects than
that with other drugs such as OK-432, talc, glucose and minocycline
hydrochloride\textsuperscript{13} Therefore, pleurodesis with autologous
blood is a better strategy for refractory pneumothorax in patients with
poor general condition after severe COVID-19 infection. In case of
inoperable patients with refractory pneumothorax after severe COVID-19
infection, bronchial occlusion and pleurodesis can be key treatment
strategies.

\textbf{CONCLUSION}

Bilateral pneumothorax can occur as a complication of COVID-19
infection. Refractory pneumothorax in severe COVID-19 patients with poor
general condition may be inoperable. In such situations, combining
internal treatments such as chest drainage, bronchial occlusion and
pleurodesis is essential for relieving refractory pneumothorax.

\textbf{DISCLOSURE STATEMENT} : The authors declare no conflicts of
interest (COI).

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Chen N, Zhou M, Dong X, et al. Epidemiological and clinical
  characteristics of 99 cases of 2019 novel coronavirus pneumonia in
  Wuhan, China: a descriptive study. \emph{Lancet} . 2020;395:507--513.
\item
  Mallick T, Dinesh A, Engdahl R, et al. COVID-19 complicated by
  spontaneous pneumothorax. \emph{Cureus} . 2020;12:e9104.
\item
  Sayar, A, Turna A, Metin M, et al. Simultaneous bilateral spontaneous
  pneumothorax report of 12 cases and review of the
  literature.\emph{Acta Chir Belg} . 2004;104:572-576.
\item
  Liu K, Zeng Y, Xie P, et al. COVID-19 with cystic features on computed
  tomography: a case report. \emph{Medicine (Baltimore)} .
  2020;99;18:e20175.
\item
  do Lago VC, Cezare TJ, Fortaleza CMCB, et al. Does COVID-19 increase
  the risk for spontaneous pneumothorax? \emph{Am J Med Sci} .
  2020;360:735-737.
\item
  Yamaya T, Baba T, Hagiwara E, et al. Pneumothorax in a COVID-19
  pneumonia patient without underlying risk factors. \emph{Intern Med} .
  2020;59:2921-2925.
\item
  Akcam TI, Kavurmaci O, Ergonul AG, et al. Analysis of the patients
  with simultaneous bilateral spontaneous pneumothorax. \emph{Clin
  Respir J} . 2018;12:1207-1211.
\item
  Dugan KC, Laxmanan B, Murgu S, et al. Management of persistent air
  leaks.\emph{Chest} . 2017;152:417--423.
\item
  Watanabe Y, Matsuo K, Tamaoki A, et al. Bronchial occlusion with
  Endobronchial Watanabe Spigot. \emph{J Bronchol} 2003;10:264-267.
\item
  Kaneda H, Minami K, Nakaho T, et al. Efficacy and long-term clinical
  outcome of bronchial occlusion with endobronchial Watanabe spigot for
  persistent air leaks. \emph{Respir Investig} 2015;53:30-36.
\item
  Lois M, Noppen M. Bronchopleural fistulas: an overview of the problem
  with special focus on endoscopic management.
  \emph{Chest}2005;128:3955-3965.
\item
  Mitsuyama Y, Tanaka S, Ike A et al. Refractory pneumothorax secondary
  to COVID-19 treated by autologous blood patch pleurodesis. \emph{QJM}
  . 2022;114:803-804.
\item
  Aihara K, Handa T, Nagai S, et al. Efficacy of blood-patch pleurodesis
  for secondary spontaneous pneumothorax in interstitial lung
  disease.\emph{Intern Med} . 2011;50:1157-1162.
\end{enumerate}

Figure 1.

A, B: Contrast computed tomography on admission shows infiltration
shadows on both sides

C: Computed tomography shows bilateral pneumothorax after bilateral tube
drainage.

D: Flexible bronchoscopy shows bronchial obstruction using
EWS\textsuperscript{(r)} (a 6-mm EWS\textsuperscript{(r)} into B8b\selectlanguage{english}i and a
7-mm EWS\textsuperscript{(r)} into B8b\selectlanguage{english}ii on the left).

\textbf{Hosted file}

\verb`Bilateral pneumothorax figures submission.pptx`  available at \url{https://authorea.com/users/520608/articles/593881-bilateral-refractory-pneumothorax-treated-by-pleurodesis-and-bronchial-occlusion-in-a-covid-19-patient}

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

