\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{Bronchopleural fistula associated persistent pneumothorax in a patient
recovering from COVID-19 pneumonia: A case report}



\author[1]{Milan Regmi}%
\author[1]{Anurag Karki}%
\author[1]{Moon Shrestha}%
\author[1]{Nibesh  Pathak}%
\author[1]{Sanjeev Bhandari}%
\author[1]{Niraj Sharma}%
\author[1]{Pankaj  Pant}%
\affil[1]{Tribhuvan University Institute of Medicine}%


\vspace{-1em}



  
  \date{May 18, 2024}


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








\sloppy


\textbf{Introduction}

Coronavirus belongs to RNA viruses that cause respiratory, neurologic,
enteric, and hepatic diseases distributed among mammals, including
humans and birds (1). A novel coronavirus discovered in late 2019 in
China caused Coronavirus Disease 2019 (COVID-19). It is associated with
complications like severe viral pneumonia, ARDS, AKI, cardiac injury,
liver dysfunction, spontaneous pneumothorax, lung cavitation, pleural
effusion, pericardial effusion, along with other minor ailments like
fever, loss of smell, myalgia, dry cough, lymphadenopathy (2) (3).

Pneumothorax due to COVID-19 pneumonia is very rare, and few cases are
reported with bronchopleural fistula-associated persistent pneumothorax
while recovering from COVID-19 pneumonia (4) (5) (6).

\textbf{Case History}

A 57-year-old male with shortness of breath, fever, dry cough, and chest
pain was admitted to our center. Six weeks back, he was diagnosed with
COVID-19 on RT-PCR and was being managed at another center with oxygen
via nasal cannula at 2L/minute. However, due to the increased severity
of his symptoms, he was referred to our center.

His medical history was notable for type 2 diabetes mellitus and
hypertension for six years. He had been non-compliant with his
medication for one year. He had a myocardial infarction two years back,
for which coronary artery grafting was performed. He also had features
of hypertensive heart disease with mild concentric left ventricular
hypertrophy and grade 2 left ventricular diastolic dysfunction.

The physical examination at admission revealed an ill-looking patient
with bilateral crepitations. Blood investigations showed a fasting blood
glucose level of 165.3 mg/dl and a post-prandial glucose level of 226.6
mg/dl. He was managed with IV antibiotics, heparin, insulin on a sliding
scale, and other supplemental medications. He developed an acute kidney
injury with hyperkalemia during the course, which resolved after three
days.

On the 10th day of admission, he had worsening shortness of breath and
an inability to maintain saturation at an oxygen flow rate of 2Lit/min.
Therefore, a chest X-ray (Figure: 1a) was performed, which showed a
right-sided pneumothorax associated with bilateral lung opacities.
However, a chest X-ray performed six days after admission showed no
findings suggesting pneumothorax (Figure 1b).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Figure 1a. Chest X-ray showed bilateral lung opacities with a
visible visceral pleural line, absent lung markings, and peripheral
radiolucency on the right side, suggesting pneumothorax.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 1b. Chest X-ray showing bilateral lung opacities (before
pneumothorax)}

The patient was managed with a non-rebreather face mask with an oxygen
flow rate of 15 L/minute, and a chest tube was inserted at the fourth
intercostal space to drain the pneumothorax. Despite those measures, he
deteriorated, for which an HRCT chest was ordered. HRCT scan (Figure 2a,
Figure 2b.) revealed a right hydropneumothorax with passive right lung
atelectasis and an intermediate walled cavity in the right lower lobe
with bronchopleural fistula. Also, multifocal ground glass
consolidations were seen predominantly in bilateral peripheral lung
fields with fibro-bronchiectatic changes with crazy pavement patterns
suggesting sequelae of COVID-19 pneumonia.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 2a.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 2b.}

\textbf{Figure 2a and Figure 2b are HRCT scans showing right-sided
hydropneumothorax with an intermediate walled cavity in the right lower
lobe with BPF and multifocal consolidation with ground glass in
bilateral lung fields with fibro bronchiectatic changes and crazy
pavement patterns.}

The patient showed no sign of improvement even after placement of the
chest tube for three days. Therefore, a repeat chest X-ray had to be
performed that revealed minimal re-expansion of the right lung,
indicating persistent pneumothorax. For this, the chest tube's
functionality was assessed, which showed signs of leakage, and a second
chest tube had to be inserted. Despite implementing all necessary and
aggressive interventions, the patient's overall condition continued to
deteriorate, necessitating collaboration with the thoracic surgical team
to plan a surgical procedure for repairing the bronchopleural fistula.
Regrettably, despite efforts to stabilize the patient, his condition
deteriorated rapidly, resulting in an unfortunate outcome.

\textbf{Discussion:}

Pneumothorax is the presence of air in pleural space, which can be
broadly classified as spontaneous and traumatic (7). Spontaneous
pneumothorax not associated with any underlying lung disease is called
primary, and those associated with some underlying lung disease are
categorized as secondary (7). Our patient, who was in the recovery phase
of COVID-19, experienced a spontaneous pneumothorax. Given the
association with COVID-19 pneumonia, this condition was classified as a
secondary spontaneous pneumothorax. The occurrence of pneumothorax in
COVID-19 patients varies, with a range of 0.3\% in hospitalized
individuals and a higher prevalence of 12.8\% to 23.8\% among those who
require mechanical ventilation(8). A study by Chong et al. did not
identify age or active smoking status as a risk factor for
COVID-19-related pneumothorax (8). Our patient smoked one pack of
cigarettes daily and stopped just after he was diagnosed with COVID-19.

Studies have shown the development of subpleural bullae that are visible
on X-ray or CT scans before the occurrence of spontaneous pneumothorax.
However, in our patient, a Chest X-ray (Figure 1b.) performed six days
before the development of pneumothorax didn't show any subpleural bullae
(2). Interestingly, the pneumothoraces that are caused due to COVID-19
usually tend to be right-sided and unilateral, as seen in our case as
well (8).

Conservative treatment is recommended to manage asymptomatic
pneumothorax, i.e., without significant breathlessness. Simple
aspiration must be performed for symptomatic cases and should be
admitted and observed for at least 24 hours(10). Intercostal drainage is
recommended for those patients who fail to respond with aspiration and
in all cases of secondary pneumothorax. The procedure is, however, not
recommended for asymptomatic secondary pneumothorax or patients with
apical pneumothorax measuring less than 1cm (10). Weissberg et al.
recommend chest tube drainage when pneumothorax occupies more than 20\%
of pleural space. In our case, more than 50\% of the pleural space on
the right lung was occupied by pneumothorax, which warranted the
placement of a chest tube(11).

However, even with the chest tube in-situ, there was minimal lung
re-expansion, which prompted further investigations to discover the
cause of persistent pneumothorax. An HRCT scan of the lungs showed the
presence of a Bronchopleural Fistula (BPF), an abnormal connection
between a bronchus and pleural space associated with very high morbidity
and mortality. Many factors are related to developing a bronchopleural
fistula, including necrotizing infection of the lungs, persistent
spontaneous pneumothorax, radiotherapy, and chemotherapy(9). Our patient
may have developed the fistula due to persistent spontaneous
pneumothorax. BPF may be associated with empyema of the lungs if it
persists for a long duration, for which chest drainage and long-term
antibiotics are crucial to treatment (6). In our patient, after
visualization of hydropneumothorax on HRCT, surgical consultation was
done to assess the functionality of the previously inserted chest tube
and to manage the BPF surgically. The second chest tube drain was
inserted to give negative suction pressure as the first chest tube was
not functioning correctly. Endobronchial intervention is preferred for
seriously ill patients with small-size fistulas. The endobronchial
intervention included sealing agents like glues, blood patches, or
endobronchial valves. Surgical management is usually indicated for large
bronchopleural fistula measuring more than 8 mm in size or persistent
symptomatic pneumothorax due to the BPF (6). Surgical intervention,
although planned, could not be performed as our patient succumbed to
death due to rapid deterioration, even with appropriate management.

\textbf{Conclusion}

Pneumothorax and bronchopleural fistula are rare complications of
COVID-19 pneumonia. This case report emphasizes the challenges in
managing these conditions in patients recovering from COVID-19
pneumonia. Early recognition, appropriate diagnostics, and timely
intervention are crucial for optimal outcomes. Close monitoring and
careful management are necessary for pneumothorax and bronchopleural
fistula in COVID-19 patients, with conservative or interventional
approaches based on symptoms and severity.

Further research is needed to understand the underlying mechanisms and
risk factors associated with pneumothorax and bronchopleural fistula in
COVID-19 patients. Improved knowledge in this area will aid in
developing effective management strategies and ultimately improve
patient outcomes. Healthcare providers should remain vigilant for these
complications in COVID-19 patients and be prepared to intervene promptly
to minimize morbidity and mortality.

\textbf{Conflicts of Interest}

The authors have no conflict of interest to declare.

\textbf{Funding}

No funding was received for the study.

\textbf{Authors Acknowledgement}

MR conceptualized the study, reviewed, edited the manuscript, and was in
charge of the case; MS and MR wrote the original, reviewed and edited
the manuscript; AK, NP, NKS, SB, and PP reviewed the manuscript.

\textbf{Data Availability statement}

All the required information is in the manuscript itself.

\textbf{Consent Statement}

Written informed consent was taken from the patient before the
initiation of the study to publish this report.

\textbf{References:}

\textbf{1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel
Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med
{[}Internet{]}. 2020 Jan 24 {[}cited 2021 Jun 11{]}; Available
from:\emph{https://www.nejm.org/doi/10.1056/NEJMoa2001017}}

\selectlanguage{ngerman}\textbf{2. Spiro JE, Sisovic S, Ockert B, Böcker W, Siebenbürger G.
Secondary tension pneumothorax in a COVID-19 pneumonia patient: a case
report. Infection. 2020 Dec 1;48(6):941--4.}

\textbf{3. Ucpinar BA, Sahin C, Yanc U. Spontaneous pneumothorax and
subcutaneous emphysema in COVID-19 patient: Case report. J Infect Public
Health. 2020 Jun 1;13(6):887--9.}

\textbf{4. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al.
Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet.
2020 Feb 15;395(10223):507--13.}

\textbf{5. Sun R, Liu H, Wang X. Mediastinal Emphysema, Giant Bulla, and
Pneumothorax Developed during the Course of COVID-19 Pneumonia. Korean J
Radiol. 2020 May;21(5):541--4.}

\textbf{6. Talon A, Arif MZ, Mohamed H, Khokar A, Saeed AI.
Bronchopleural Fistula as a Complication in a COVID-19 Patient Managed
With Endobronchial Valves. J Investig Med High Impact CaseRep. 2021 Jan
1;9:23247096211013216.}

\textbf{7. Noppen M, De Keukeleire T. Pneumothorax. Respiration.
2008;76(2):121--7.}

\textbf{8. Chong WH, Saha BK, Hu K, Chopra A. The incidence, clinical
characteristics, and outcomes of pneumothorax in hospitalized COVID-19
patients: A systematic review. Heart Lung. 2021 Sep 1;50(5):599--608.}

\textbf{9. Henry M, Arnold T, Harvey J. BTS guidelines for the
management of spontaneous pneumothorax. Thorax. 2003 May;58(Suppl
2):ii39--52.}

\textbf{10. Weissberg D, Refaely Y. Pneumothorax: Experience With 1,199
Patients. Chest. 2000 May 1;117(5):1279--85.}

\textbf{11. Placik DA, Taylor WL, Wnuk NM. Bronchopleural fistula
development in the setting of novel therapies for acute respiratory
distress syndrome in SARS-CoV-2 pneumonia. Radiol Case Rep. 2020 Nov
1;15(11):2378--81}

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

