\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,greek,english]{babel}



\usepackage{float}








\begin{document}

\title{A novel respiratory device and the application of cardiorespiratory
performance to hemodialysis patients}



\author[1]{Kornanong Yuenyongchaiwat}%
\author[2]{Chusak  Thanawattano}%
\author[2]{Chatchai  Buekban}%
\author[1]{Noppawan  Charususin}%
\author[1]{Karan  Pongpanit}%
\author[1]{Somrudee  Hanmanop}%
\author[1]{Phuwarin  Namdang}%
\author[3]{Opas  Traitanon}%
\affil[1]{Thammasat University - Rangsit Campus}%
\affil[2]{National Electronics and Computer Technology Center}%
\affil[3]{Thammasat University Faculty of Medicine}%


\vspace{-1em}



  
  \date{May 10, 2024}


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





\selectlanguage{english}
\begin{abstract}
Background: Muscle wasting and limitation in physical activity have been
reported in patients with hemodialysis; this leads to poor quality of
life at the end. Objective: To develop the respiratory training device
and to determine the efficiency of the prototype on respiratory muscle
strength, functional capacity and dyspnea perception in hemodialysis
patients. Design, setting and participants: the development of
respiratory device was created and then effects of respiratory device
were examined in hemodialysis patients. A total of 25 patients with
quasi experimental study was recruited in the present study with aged [?]
35 years old. All participants had a history of hemodialysis 3 days per
week. Outcome measurements and statistical analysis: The protocol was
conducted 15 inhales, three set per day with 40\% of maximal inspiratory
pressure; totally 45 inhales. The participants were asked to perform for
three times per week during on hemodialysis. Respiratory muscle
strength, the 6minute walk test and rate of dyspnea scores were assessed
before and after 8-week intervention program. Paired t-tests was used to
compare between initial values and follow-up values in respiratory
prototype. Results: Of 25 patients at initially was enrolled, 22
individuals (88\%) completed in the 8-week program. Significant improve
in inspiratory muscle strength, 6minite walk distance and rate of
dyspnea was observed after 8-week intervention (?12.44\selectlanguage{ngerman}± 3.55 cmH2O,
\selectlanguage{english}?24.78 +- 8.89 meters, and \selectlanguage{english}?0.50 +- 0.19, respectively). Conclusion: Using
porotype of respiratory device can effectively improve cardiorespiratory
performance which is marked by increasing inspiratory muscle functional
capacity and rate of dyspnea in hemodialysis patients after 8-week
training program.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{A novel respiratory device and the application of
cardiorespiratory performance to hemodialysis patients}

\textbf{Abstract:}

\textbf{Background:} Muscle wasting and limitation in physical activity
have been reported in patients with hemodialysis; this leads to poor
quality of life at the end.

\textbf{Objective:} To develop the respiratory training device and to
determine the efficiency of the prototype on respiratory muscle
strength, functional capacity and dyspnea perception in hemodialysis
patients.

\textbf{Design, setting and participants:} the development of
respiratory device was created and then effects of respiratory device
were examined in hemodialysis patients. A total of 25 patients with
quasi experimental study was recruited in the present study with aged [?]
35 years old. All participants had a history of hemodialysis 3 days per
week.

\textbf{Outcome measurements and statistical analysis:} The protocol was
conducted 15 inhales, three set per day with 40\% of maximal inspiratory
pressure; totally 45 inhales. The participants were asked to perform for
three times per week during on hemodialysis. Respiratory muscle
strength, the 6minute walk test and rate of dyspnea scores were assessed
before and after 8-week intervention program. Paired t-tests was used to
compare between initial values and follow-up values in respiratory
prototype.

\textbf{Results:} Of 25 patients at initially was enrolled, 22
individuals (88\%) completed in the 8-week program. Significant improve
in inspiratory muscle strength, 6minite walk distance and rate of
dyspnea was observed after 8-week intervention (\selectlanguage{greek}Δ\selectlanguage{english}12.44\selectlanguage{ngerman}± 3.55
cmH\textsubscript{2}O, \selectlanguage{greek}Δ\selectlanguage{english}24.78 \selectlanguage{ngerman}± 8.89 meters, and \selectlanguage{greek}Δ\selectlanguage{english}0.50 \selectlanguage{ngerman}± 0.19,
respectively).

\textbf{Conclusion:} Using porotype of respiratory device can
effectively improve cardiorespiratory performance which is marked by
increasing inspiratory muscle functional capacity and rate of dyspnea in
hemodialysis patients after 8-week training program.

\textbf{Keywords:} respiratory device, hemodialysis, dyspnea,
respiratory muscle, functional capacity, rehabilitation

Thai Clinical Trials Registry (TCTR) number is TCTR20171107003.

\textbf{Introduction}

Muscle wasting and limitation in physical activity have been reported in
patients with end stage renal disease. In addition, myopathy uraemia has
been described in chronic renal failure (CRF), and this leads to decline
in muscle strength including respiratory muscle. It has been reported
that respiratory muscle training in CRF patients could increase in
respiratory muscle strength and thereby increase in functional
capacity\textsuperscript{1}. Pellizzaro et al reported the effect of
respiratory muscle training in CRF patients during hemodialysis and
found that respiratory muscle strength and functional capacity had a
significantly improvement while the control group who did not any
intervention were not improved \textsuperscript{1}. In addition, a
correlation was found between inspiratory muscle strength and functional
capacity (defined as the 6-minute walk test). Inspiratory muscle
training (IMT) commonly performs a threshold loading IMT such as
POWERbreathe. Using the threshold loading IMT should inspire through a
mouthpiece with adjusted or different resistance in the inspiration.
Therefore, inspiratory muscle training might be carried by using
accessory muscle for example scalene muscle or sternocleidomastoid
muscle. According to the previous study, we created a respiratory
prototype (named TU-Breath Training) that attached on the lower costal
muscle instead. Further, it has been shown that training with TU-breathe
could reduce blood pressure in hypertensive participants
\textsuperscript{2}. Therefore, the study was aimed to design and
develop a new prototype of respiratory version II and explore the effect
of the prototype version II on cardiorespiratory performance (i.e.,
respiratory muscle strength, functional capacity) and dyspnea score
among hemodialysis patients.

\textbf{2. Materials and Methods}

The Research has been approved from the Ethics Committee on Human
Subject of Thammasat University and the Ethics in Human Research
Committee of the Thammasat University Hospital, according to the
principles of the Declaration of Helsinki 1975.

Participants were adults aged 30-75 years old both males and females.
Further, those had been diagnosed end stage renal failure at stage 5 and
receiving hemodialysis more than three months, undergoing hemodialysis
three times a week for 3-4 hours per day. The exclusion criteria were
participants who had been resting systolic blood pressure greater than
200 mmHg and/or diastolic blood pressure greater than 120 mmHg, had
neurological problems (e.g., stroke, had musculoskeletal problems (e.g.,
severe osteoarthritis, ambulation), uncontrolled pulmonary disease,
mental health problems (diagnosis from doctor or psychiatrist) and
cognitive impairment.

Prior to the training program, the participants were explained the
objective and methodology of the study. Next, participants were asked to
sign the informed consent and fill in a questionnaire, such as medical
history, duration of hemodialysis, history of drinking and smoking.
Participants performed respiratory muscle strength testing. Maximal
inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were
measured by a mouth pressure meter (Micromedical generation, micro DL
no.2, Carefusion company). Participants were asked to sit on a chair
comfortably and the noseclip was attached. After that, individuals were
requested to take a deep breath near to residual volume and inhale
deeply with hold on 1.5 seconds this could be defined as MIP. Next, for
the MEP, participants take a deep breath near to total lung capacity and
exhale fast and then hold on 1.5 seconds. Participants were requested to
repeat the tests for three to five times and maximal value was
recorded\textsuperscript{3}. Participants rest for five minutes or rest
until heart rate recovery. Prior to the functional capacity testing
(i.e., the 6-minute walk test: 6MWT), the participants were recorded
blood pressure, heart rate, rate perceived exertion (RPE: modified Borg
scale 0-10) and oxygen saturation Participants performed the 6MWT which
is long level corridor 30 meters and walk within six
minutes\textsuperscript{4}. Blood pressure, heart rate, RPE and oxygen
saturation were re-assessed after 6MWT. The perception of breathlessness
is rated on a Likert scale between 1 (very difficult to breath) and 5
(not difficult to breath). Participants were asked to complete how
difficult breath during the past month.

The respiratory muscle training program was used by the prototype of
respiratory muscle training version II (TU-breathe V. 2); see Figure 1.
The system composes an air resistive respiration training device
including a respiration sensor. The pressure sensor is connected to the
respiratory sensor and it is sent the pressure value via Bluetooth which
has been installed by a smartphone. The pressure sensor and system have
been described in detail elsewhere \textsuperscript{2}.

The participants were asked to take a deep breath in deeply and the
maximal pressure value was shown and recorded. After that, the
participants were required to take deep breath in for 40\% of maximal
inspiration, 15 times/ sets for 3 sets, interval 60 seconds. Respiratory
muscle strength was reassessed after 4-week intervention for adjusting
respiratory loading. Functional capacity and respiratory muscle strength
were performed after 8-week intervention program.

The data analysis was calculated with SPSS program version 20. The
statistically significance is set \emph{p} value less than 0.05.
Kolmogorov - Smirnov (Goodness of fit) test was used for test of
distribution data. Paired t-test was performed to evaluate the effect of
breathing training on respiratory muscle strength, functional capacity
and sensation of breathlessness in pre and post training program (before
vs. after 8-week intervention).

\par\null

\textbf{3. Results}

A total of 25 participants were enrolled at initial session; however,
three participants who did not complete the program because their busy.
Therefore, results were recruited 22 participants (88.0\%). There were
no significant differences in initial characteristic data between those
who complete the study program and those who did not
(\emph{p\textsubscript{s}} \textgreater{} .005). The demographic,
cardiorespiratory performance and rate of dyspnea of the hemodialysis
patients at baseline and follow-up are shown in table 1.

Paired t-tests was used to compare between initial values and follow-up
values in respiratory prototype (table 2); these indicated that
respiratory training with TU-Breath Training version II had increased
significantly from initial period to the 8 weeks intervention (\selectlanguage{greek}Δ\selectlanguage{english}14.23\selectlanguage{ngerman}±
3.44, 95\%CI = 7.13 to 21.32, p \textless{}.001). The walking distance
was also increased in TU-Breath Training group after 8-weeks (\selectlanguage{greek}Δ\selectlanguage{english}20.09 \selectlanguage{ngerman}±
9.10 meters, 95\%CI = 1.17 to 39.02, \emph{p} = .039). Again, the
efficacy of TU-Breath Training was reported in increased perceived of
dyspnea scores after intervention program (\selectlanguage{greek}Δ\selectlanguage{english}0.50 \selectlanguage{ngerman}± 0.16, 95\%CI = 0.17
to 0.83, \emph{p} = .005).

\textbf{4. Discussion}

The purposes of the study were to develop the respiratory device
training (named TU-Breath Training version II) and examine the effect of
the prototype on cardiorespiratory performance (i.e., respiratory muscle
strength and functional capacity) and rate of dyspnea in hemodialysis
patients. The study reported that use of respiratory prototype program
could improve respiratory muscle strength, functional capacity and rate
of dyspnea in hemodialysis patients. These results are in line with the
previous studies \textsuperscript{1, 5-8}.

The study was revealed that an improvement in MIP, 6MWD and sensation of
breathlessness were observed in inspiratory muscle training thought
respiratory prototype (TU-Breath Training version II). Dysfunction in
multiple systems (e.g., musculoskeletal, cardiovascular and respiratory
systems) could be found in patients with CRF. The reduction of systemic
protein and skeletal muscle mass leads to loss of muscle mass whether in
type I or type II fibers in cross-sectional areas. Further, the
proportion of show fibers and also in the size of the fast fibers can
been improved inspiratory muscle training \textsuperscript{9}. Muscle
atrophy in particular type II muscle fibers, results from a reduction of
vascular and capillary blood flow \textsuperscript{10}. These results
are part of uremic myopathy in relation to skeletal muscles including
the diaphragm and intercostal muscle and may present in muscle weakness
(decreased MIP) and poor functional capacity (i.e.,
6-MWT)\textsuperscript{11}. In addition, impaired respiratory muscle by
the uremic neuropathy and myopathy could leads to increases the work of
breathing and also the neuromuscular dissociation \textsuperscript{11}.
Therefore, neuromuscular dissociation might provoke an increase in
respiratory effort and perceived in breathlessness among patients with
chronic renal failure \textsuperscript{12}. In addition, weakness of
inspiratory muscle leads to increase respiratory effort during exercise
or physical activity resulting to increase metabolic stress in
respiratory muscle and metaboreflex stimulation \textsuperscript{13}.
Thus, metaboreflex stimulus and uremic myopathy might partially explain
why respiratory muscle training improved sensation of breathlessness and
cardio-respiratory fitness (i.e., inspiratory muscle strength and
6-MWT).

Regarding to breathlessness, the study found a decrease of dyspnea after
8-week intervention program. Silva et al found an improvement in the
sensation of breathlessness after inspiratory muscle training program in
hemodialysis patients \textsuperscript{8}. Decreased dyspnea is reported
in IMT, it might be a decreasing dynamic hyperinflation of rib cage and
therefore increasing gas exchange \textsuperscript{14}. In addition,
increased respiratory muscle strength can be enhancing the pattern of
maximal thoraco-abodminal motion \textsuperscript{(14)}. Additionally,
Patessio et al reported the relationship between the sensation of
breathlessness and respiratory muscle strength \textsuperscript{15}. MIP
less than 80 cmH20 has been defined as inspiratory muscle
weakness\textsuperscript{3,16}. In the present study, MIP was an average
68.32 cmH2O which is clinically important inspiratory muscle weakness.
However, after training programme for 8-week, the improvement in
inspiratory muscle rose to 82.55 cmH\textsubscript{2}O. Therefore, it
might be, in part, inspiratory muscle training improved the inspiratory
muscle strength and thereby decreased sensation of breathlessness.

Some limitations of the present study should be noted. A relative small
sample size with quasi experimental design which is lack of a control
group. Therefore, further study need to explore the effect of
inspiratory muscle training with a large sample size and randomized
control trails. In addition, the training protocol such as intensity,
frequency and duration of the study should be a consideration that might
affect the result of the study.

\textbf{5. Conclusion}

IMT with the prototype of respiratory device displayed significantly
improved inspiratory muscle, functional capacity and decreased sensation
of breathless after 8-week intervention program.

\textbf{Declaration of conflicting interests}

There are no conflicts of interest in the study.

\textbf{Funding}

The financial support provided by a research grant from the National
Research Council of Thailand.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Pellizzaro CO, Thomé FS, Veronese FV. Effect of peripheral and
  respiratory muscle training on the functional capacity of hemodialysis
  patients. \emph{Ren Fail} . 2013; 35: 189--197.
\item
  Yuenyongchaiwat K, Thanawattano C, Buranapuntalug, S, Pongpanit K,
  Saengkrut P. Development of respiratory device and the immediate
  effect of prototype of respiratory device on blood pressure in adults
  with high blood pressure. \emph{Interv Med Appl Sci.}2019;11(1):21-26.
\item
  American Thoracic Society/European Respiratory Society. ATS/ERS
  statement on respiratory muscle testing. \emph{Am J Respir Crit Care
  Med} . 2002; 166:518-624.
\item
  American Thoracic Society. ATS statement: guidelines for the
  six-minute walk test. \emph{Am J Respir Crit Care Med} . 2002; 166:
  111-117.
\item
  Figueiredo RR, Castro AAM, Napoleone FMGG, Faray L, de Paula Júnior
  AR, Osorio, RAL. Respiratory biofeedback accuracy in chronic renal
  failure patients: a method comparison. \emph{Clin Rehabil} . 2002; 26:
  724--732.
\item
  Figueiredo PHS, Lima MMO, Costa HS, Martins JB, Flecha OD, Goncalves
  PF, et al. Effects of the inspiratory muscle training and aerobic
  training on respiratory and functional parameters, inflammatory
  biomarkers, redox status and quality of life in hemodialysis patients:
  A randomized clinical trial. \emph{PLos One} . 2018; 13(7): e0200727.
  https://doi.org/10.1371/journal.pone.0200727
\item
  El-Deen HAB, Alanazi FS, Ahmed KT. Effects of inspiratory muscle
  training on pulmonary functions and muscle strength in sedentary
  hemodialysis patients. \emph{J Phys Ther Sci} . 2018; 30:424-427.
\item
  Silva VG, Amara C, Monteiro MB, Nascimento DM, Boschetti JR. Effects
  of inspiratory muscle training in hemodialysis patients. \emph{J Bras
  Nefrol} . 2011; 33: 62--68. pmid:21541465
\item
  Polla B, D'Antona G, Bottinelli R, Reggiani C. Respiratory muscle
  fibres: specialisation and plasiticity. \emph{Thorax.} 2004; 59:
  808--817. doi: 10.1136/thx.2003.009894
\item
  Sakkas GK, Ball D, Mercer TH, Sargeant AJ, Tolfrey K, Naish PF.
  Atrophy of non-locomotor muscle in patients with end-stage renal
  failure. \emph{Nephrol Dial Transplant} . 2003; 18(10) 2074-2081.
\item
  Cury JL, Brunetto AF, Aydos RD. Negative effects of chronic kidney
  failure on lung function and functional capacity. \emph{Rev Bras
  Fisioter} . 2010; 14(2):91- 98.
\item
  Palamidas AF, Gennimata SA, Karakontaki F, Kaltsaka G, Papantoniou I,
  Koutsoukou, A, et al. Impact of hemodialysis on dyspnea and lung
  function in end stage kidney disease patients. \emph{Biomed Res Int} .
  2014; 2014: 212751. doi: 10.1155/2014/212751
\item
  Figueiredo PHS, Lima MMO, Costa HS, Gomes RT, Neves, CDC, de Oliveira
  ES, et al. The role of the inspiratory muscle weakness in functional
  capacity in hemodialysis patients. \emph{PLoS One} . 2017; 12(3):
  e0173159. doi: 10.1371/journal.pone.0173159
\item
  Patessio A, Rampulla C, Fracchia C, Ioli F, Majani U, De Marchi A, et
  al. Relationship between the perception of breathlessness and
  inspiratory resistive loading: report on a clinical trial. \emph{Eur
  Respir J Suppl} . 1998; 7: 587s-591s.
\item
  Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dube BP,
  et al. ERS statement on respiratory muscle testing at rest and during
  exercise. \emph{Eur Respir J} . 2019; 53:1801214, DOI:
  10.1183/13993003.01214-2018
\item
  McConnell AK, Romer LM. Dyspnoea in health and obstructive pulmonary
  disease: the role of respiratory muscle function and
  training.\emph{Sports Med} . 2004; 34: 117--132. doi:
  10.2165/00007256-200434020-00005.
\end{enumerate}

\textbf{Figure Legends}

\emph{Figure 1: prototype of respiratory muscle training version II
(TU-breathe V. 2)}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-prototype-of-respiratory-muscle-training-version-II-(TU-breathe-V/Figure-1-prototype-of-respiratory-muscle-training-version-II-(TU-breathe-V}

\end{center}
\end{figure}

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

