\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[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Objective measurement and patient-reported evaluation of the nasal
airway -- is correlation dependent on symptoms or on nasal airflow?}



\author[1]{Rui Xavier}%
\author[2]{Sofia Azeredo}%
\author[3]{Dirk Jan Menger}%
\author[1]{Henrique Carvalho}%
\author[4]{Jorge Spratley}%
\affil[1]{Universidade do Porto Instituto de Ciencias Biomedicas Abel Salazar}%
\affil[2]{Universidade Nova de Lisboa Faculdade de Ciencias Medicas}%
\affil[3]{University Medical Center Utrecht}%
\affil[4]{Universidade do Porto Faculdade de Medicina}%


\vspace{-1em}



  
  \date{May 15, 2024}


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





\selectlanguage{english}
\begin{abstract}
Abstract Background: Evidence showed that the sensation of nasal
breathing is related to variations in nasal mucosa temperature produced
by airflow. An appropriate nasal airflow is necessary for changing
mucosal temperature. Therefore, the correlation between objective
measurements of nasal airflow and patient-reported evaluation of nasal
breathing should be dependent on the level of nasal airflow. Objectives:
To find if the correlation between patient-reported assessment of nasal
breathing and objective measurement of nasal airflow is dependent on the
severity of symptoms of nasal obstruction or on the level of nasal
airflow. Methods: The airway of 79 patients was evaluated using NOSE
score and peak nasal inspiratory flow (PNIF). Three subgroups were
created based on NOSE and three subgroups were created based on PNIF
level to find if correlation was dependent on nasal symptoms or airflow.
Results: The mean value of PNIF for the 79 patients was 92.6 l/min (SD
28.1 l/min). The mean NOSE score was 48.4 (SD 24.4). The correlation
between PNIF and NOSE was statistically significant (p=0.03), but with a
weak association between the two variables (r=-0.248). Evaluation of
correlation based on symptoms demonstrated a weak or very weak
association in each subgroup (r=-0.250, r=-0.007, r=-0.104). Evaluation
of correlation based on nasal airflow demonstrated a very weak
association for the subgroups with middle-level and high PNIF values
(r=-0.190, r=-0.014), but a moderate association for the subgroup with
low PNIF values (r=-0.404). Conclusions: This study demonstrated a weak
correlation between NOSE scores and PNIF values in patients non-selected
according to symptoms of nasal obstruction or to airflow. It
demonstrated that patients with symptoms of nasal obstruction have
different levels of nasal airflow and that low nasal airflow prevents
the sensation of good nasal breathing. Therefore, patients with symptoms
of nasal obstruction may require improving nasal airflow to improve
nasal breathing sensation.%
\end{abstract}%



\sloppy


\textbf{Keywords}

Nasal airway evaluation, Objective and Patient-Reported evaluation
correlation, Correlation based on symptoms, Correlation based on
airflow, NOSE, PNIF

\textbf{Keypoints}

\begin{itemize}
\tightlist
\item
  Evidence has shown that the sensation of nasal breathing is related to
  nasal mucosa temperature variation produced by airflow. An appropriate
  nasal airflow is necessary for changing mucosal temperature.
  Therefore, the correlation between objective measurements of nasal
  airflow and patient-reported evaluation of nasal breathing should be
  correlated to the level of nasal airflow.
\item
  The airway of 79 patients was evaluated using NOSE score and peak
  nasal inspiratory flow (PNIF). Three subgroups were created based on
  NOSE score and three subgroups were created based on PNIF level to
  find if correlation between NOSE and PNIF was dependent on nasal
  symptoms or on nasal airflow.
\item
  The mean value of PNIF for the 79 patients was 92.6 l/min (SD 28.1
  l/min). The mean NOSE score was 48.4 (SD 24.4). The correlation
  between PNIF and NOSE was statistically significant (\emph{p} =0.03),
  but with a weak association between the two variables (\emph{r}
  =-0.248). Evaluation of correlation based on symptoms demonstrated a
  weak or very weak association in each subgroup (\emph{r} =-0.250,
  \emph{r} =-0.007, \emph{r} =-0.104). Evaluation of correlation based
  on nasal airflow demonstrated a very weak association for the
  subgroups with middle-level and high PNIF values (\emph{r} =-0.190,
  \emph{r} =-0.014), but a moderate association for the subgroup with
  low PNIF values (\emph{r} =-0.404).
\item
  This study has shown a weak correlation between objective measurement
  of nasal airflow and patient-reported evaluation of nasal breathing in
  patients not selected according to symptoms of nasal obstruction or to
  the level of nasal airflow.
\item
  This study has shown that a low nasal airflow prevents the sensation
  of a good nasal breathing. Therefore, patients with symptoms of nasal
  obstruction and inappropriate nasal airflow may require improving
  nasal airflow as an essential step to improve nasal breathing
  sensation.
\end{itemize}

\textbf{Introduction}

Nasal obstruction is a common complaint of patients undergoing nasal
surgery. At the present, several methods are available for assessing the
nasal airway. These methods can be divided in two main groups: methods
that objectively measure nasal airflow or nasal airway dimensions, and
methods based on patient-reported evaluation of nasal breathing.

In theory, objective measurements and patient-reported evaluations of
nasal breathing should correlate. If objective methods measure an
appropriate nasal airflow then the patient should experience a suitable
sensation of good nasal breathing. Therefore, the patient-reported
evaluation should reflect that sensation and should correlate with the
objective evaluation. However, previous studies have not found
statistical correlation between objective measurements of nasal airflow
and patient-reported evaluations of nasal breathing (1-10). Some studies
have found correlations between nasal resistance and symptoms of nasal
obstruction in patients symptomatic for nasal obstruction (11-16),
whereas other studies did not find any correlation even in symptomatic
patients (18-20). Hence, there is still a great amount of controversy in
the literature that deserves further investigation.

A growing body of evidence indicates that the sensation of nasal
breathing is more related to variations in nasal mucosa temperature due
to the cooling effect of the airstream than to variations in the nasal
airflow (8,21-23). According to these studies, an adequate nasal airflow
is necessary for providing temperature changes in the nasal mucosa. As
such, the correlation between objective measurements of nasal airflow
and patient-reported evaluation of nasal breathing should be not only
dependent on symptoms of nasal obstruction but should also be dependent
on the level of nasal airflow.

The current study had a three-fold purpose: to find if there is
correlation between patient-reported assessments of nasal breathing and
objective measurements of nasal airflow; to find if this correlation is
dependent on the severity of symptoms of nasal obstruction; and to find
if this correlation is dependent on the level of nasal airflow.

\textbf{Methods}

A series of 79 consecutive Caucasian patients undergoing rhinoplasty was
studied. Nasal airway was evaluated before surgery in each patient of
this group as part of the preoperative assessment.

This series consisted of 53 women and 26 men, with ages between 17 and
68 years old (mean 36.2 y/o). Sixty-five were primary cases and 14 were
revision rhinoplasty cases. All the primary rhinoplasty cases were
looking for an aesthetic improvement of the nose, with 29 also seeking a
functional improvement of the nasal airway. For the 14 patients
undergoing revision rhinoplasty, there were several different aesthetic
indications for the revision surgery, with no functional complaints in
none of the patients in this subgroup.

In each patient the NOSE score (Nasal Obstruction Symptom Evaluation)
(24) was obtained and peak nasal inspiratory flow (PNIF) (25) was
measured before undergoing surgery. The NOSE score was chosen as
patient-reported assessment of nasal obstruction symptoms as it is a
standardized and validated disease-specific quality of life instrument
for measuring nasal obstruction (24). A version validated for the
Portuguese language (26) was used in this study. The PNIF was obtained
in each patient according to the standard rules for measuring PNIF (25).
PNIF was chosen as objective measurement of the nasal airflow as its
results not only measure nasal airflow but also correlate with nasal
resistance (27). Furthermore, this method, together with rhinomanometry,
has been found to strongly reflect both presence and severity of nasal
airway obstruction (28).

Three groups of patients were created according to the symptoms of nasal
obstruction reported by the patients: patients with NOSE score equal to
or less than 35 (N=24), patients with NOSE score between 36 and 64
(N=26) and patients with a NOSE score equal to or higher than 65 (N=29).

Three other groups of patients were created according to the level of
nasal airflow: patients with PNIF equal to or less than 70 l/min (N=20),
patients with PNIF between 71 l/Min and 109 l/min (N=39) and patients
with PNIF equal to or higher than 110 l/min (N=20).

Statistical analysis was made for the total population of this study and
for each of the groups created based on NOSE score and on PNIF value.
Mean and standard deviations (SD) were obtained for the PNIF and NOSE
scores. A multivariable linear regression model was performed in order
to investigate the association between the NOSE scores and the PNIF
values after adjusting for age and gender of the individuals. The
estimated correlation coefficient was obtained for the PNIF score and
NOSE value to check the strength of the association between these
measurements. The nonparametric Spearman's rank correlation coefficient
was employed. A significance level of \selectlanguage{greek}α \selectlanguage{english}= 0.05 was used throughout the
analysis. The statistical analysis was performed using the R statistical
software (29), employing the RStudio environment (30). The graphs were
obtained using the R package \emph{ggplot2} (31). The strength of the
correlation (\emph{r} ) was valued as very week for\emph{r}
\textless{}0.19, week for \emph{r} between 0.20 and 0.39, moderate for
\emph{r} between 0.40 and 0.59, strong for \emph{r} between 0.60 and
0.79 and very strong for \emph{r} between 0.80 and 1 (32).

\textbf{Results}

The mean value of PNIF for this series of 79 patients was 92.6 l/min (SD
28.1 l/min). The mean NOSE score for this group of patients was 48.4 (SD
24.4). The boxplots for these values are displayed in Figure 1 and in
Figure 2, respectively.

The scatter plot and the simple regression line of best fit together
with 95\% confidence bands are shown in Figure 3. It can be observed
that there is a decrease in NOSE scores as PNIF values increase, showing
a negative correlation. This correlation is statistically significant
(\emph{p} =0.03). The multiple linear regression model demonstrated that
for an increase of one unit in NOSE score, PNIF decreases on average
0.25l/min, 95\% CI (-0.51, 0.008) p=0.057, when adjusting for age and
gender (Table 1). The estimated correlation coefficient between NOSE
score and PNIF value was found to be -0.248, which demonstrates a weak
association between PNIF value and NOSE score in the group of 79
patients.

In the groups allotted by the NOSE score, the scatter plot and the
simple regression line of best fit together with 95\% confidence bands
are shown in Figure 4. The estimated correlation coefficient for the
group of 24 patients with a NOSE score equal to or less than 35 was
found to be -0.250, which demonstrates a weak association between PNIF
value and NOSE score. In the group of 26 patients with a NOSE score
between 36 and 64 the coefficient of correlation between PNIF and NOSE
demonstrated a very weak association (\emph{r} =-0.007). The estimated
correlation coefficient for the group of 29 patients with a NOSE score
equal to or higher than 65 was found to be -0.104, which demonstrates a
very weak association between PNIF value and NOSE score.

In the groups allotted by the PNIF value, the scatter plot and the
simple regression line of best fit together with 95\% confidence bands
are shown in Figure 5.

The estimated correlation coefficient for the group of 20 patients with
a PNIF value equal to or less than 70 l/min was found to be -0.404,
which demonstrates a moderate association between PNIF value and NOSE
score. The estimated correlation coefficient for the group of 39
patients with a PNIF value between 71 l/min and 109 l/min was found to
be -0.190, which demonstrates a very weak association between PNIF value
and NOSE score. In the group of 20 patients with a PNIF value equal to
or higher than 110 l/min there was a very weak association between PNIF
value and NOSE score (\emph{r} =-0.014).

\textbf{Discussion}

This study found a statistically significant but weak correlation
between patient-reported evaluation of nasal breathing and objective
measurement of nasal airflow in patients not selected according to
symptoms of nasal obstruction or to the level of nasal airflow. A weak
or very weak correlation between patient-reported evaluation of nasal
breathing and objective measurement of nasal airflow was found in groups
of patients selected according to symptoms of nasal obstruction.

The current investigation supports that a moderate to high nasal airflow
does not necessarily lead to a subjective sensation of a good nasal
breathing, according to the widespread NOSE scores amongst patients with
moderate to high values of PNIF. Moreover, our results also suggest that
a low nasal airflow prevents the sensation of a good nasal breathing to
happen.

It is well established, according to Poiseuille`s Law, that airway
resistance is inversely proportional to the 4\textsuperscript{th} power
of the radius of the space passed through. Yet, several reasons may
explain why a wide nasal airway, as measured by acoustic rhinometry or
by the cross-section dimension on imaging techniques of the nasal
airway, may not necessarily correspond to a good nasal airflow. Firstly,
a nasal airway too wide can prevent the negative pressure necessary to
inhale air to be generated. Secondly, an overly wide nasal cavity may
decrease laminar airflow and significantly increase turbulent airflow,
which may disturb nasal breathing (33-35). And, thirdly, the dimensions
of the nasal airway have no relation to the resilience of the nasal
cavity walls, which is necessary to withstand the negative pressure
generated during inspiration.

Therefore, a wide nasal airway is not the sole factor for obtaining a
suitable and pleasant airflow. Objective measurements of the nasal
airflow do not always correlate with the subjective sensation of nasal
breathing, as reported in our study as well as in others` (1-10),
suggesting that factors other than an appropriate airflow are important
in determining the subjective sensation of a suitable nasal breathing.
Several reports have found that the sensation of nasal breathing is more
related to variations in nasal mucosa temperature due to the cooling
effect of the airstream than to the level of nasal airflow (8,21-23).
The sensation of nasal breathing is delivered to the brain by
non-myelinated trigeminal afferent fibers originating in receptors
located in the nasal mucosa (36-38). In this system, the target
thermoreceptor in the nasal mucosa has been identified as the
non-selective voltage-dependent cation channel transient receptor
potential melastin family member 8 (TRPM8) (39,40). These
thermoreceptors, which are distributed throughout the mucosa of the
nasal cavity (41,42) and mainly in the anterior part of the nasal airway
(37), are sensitive to temperature changes in the nasal mucosa caused by
the airstream. Mucosal cooling directly excites these receptors, as the
airstream passes through the nasal cavity, triggering trigeminal
afferent stimulation and providing perception of nasal breathing
(21-23,38,43,44).

Therefore, for an appropriate sensation of nasal breathing a nasal
cavity wide enough to allow the airstream to cool the nasal mucosa is
necessary. Bailey \emph{et al} (44) found a

negative correlation between nasal resistance and the degree of mucosal
cooling. But also an adequate nasal airflow is necessary for providing
temperature changes in the nasal mucosa. Lindemann \emph{et al} (45)
found that the increased nasal airflow during deep breathing was
associated with greater oscillations in nasal mucosal temperature and
greater sensation of airflow than in quiet resting breathing.

The mean value of PNIF in our series was noticeably lower than the mean
values that have previously been published in series with healthy
populations (26,46-49). This probably reflects the fact that our study
was performed in rhinoplasty-seeking patients, some complaining of nasal
obstruction, and not in a healthy population, as the mean NOSE score of
48.4 (SD 24.4) in our series indicates.

Previous researchers (11-16) have found correlation between
patient-reported assessment of the nasal airway and objective
measurements of nasal airway resistance or of nasal airflow to be
dependent on the severity of symptoms of nasal obstruction. Our
investigation focused on groups of patients that were created in
accordance to the degree of nasal obstruction as reflected by the NOSE
score, and found that this correlation was weak or very weak in each of
these subgroups (\emph{r} =-0.250, \emph{r} =-0.007, \emph{r} =-0.104).
These findings are in line with the results of other publications
(17-20). Our study shows that patients with symptoms of nasal
obstruction have different degrees of nasal airflow, which favors that
symptoms of nasal obstruction are not solely determined by nasal
airflow.

Based on the mean value of PNIF of our study, we split our series of 79
patients into three groups of patients, with low, moderate or high PNIF
values, and tried to find if correlation between patient-reported
assessment of the nasal airway and objective measurements of nasal
airflow was dependent on the degree of nasal airflow. This correlation
was very weak for patients with moderate or high nasal airflow value
(\emph{r} =-0.190, \emph{r} =-0.014). For patients with low PNIF value,
however, there was a moderate correlation between nasal airflow and the
NOSE score (\emph{r} =-0.404), suggesting that a low nasal airflow
prevents a good sensation of nasal breathing. These results are in favor
that an adequate nasal airflow may or may not be associated with
sensation of good nasal breathing, consistent with the assumption that
factors other than airflow play an important role on providing sensation
of nasal breathing. Our findings also suggest that an inadequate nasal
airflow will negatively act on the patient\selectlanguage{ngerman}´s sensation of a suitable
nasal breathing, probably due to insufficient nasal mucosal cooling.
This finding has important outcomes in the way patients with nasal
obstruction should be addressed. If patients with symptoms of nasal
obstruction have inadequate nasal airflow, then improving the airflow is
an essential step towards improving nasal breathing sensation.

This study was accomplished in a non-homogeneous group of patients, with
predominance of female patients. Also, the groups of patients created
based on the NOSE score and on the PNIF level were relatively small in
number, which may have influenced the low coefficients of correlation in
some of these groups. Likewise, all the patients included in the series
were rhinoplasty-seeking patients, and not randomly selected
individuals. This may have interfered on the difference between the mean
value of PNIF of this series when compared to previously published
series in healthy populations. Moreover, some of the patients included
in the study had already been submitted to nasal surgery, which may have
changed the perception of nasal breathing reflected by the NOSE score
and nasal airflow reflected by PNIF value. Nevertheless, none of the
patients undergoing revision rhinoplasty had complaints of nasal
obstruction. Lastly, the NOSE score is currently the most frequently
used patient-reported assessment of symptoms of nasal obstruction,
though having initially been developed as a patient reported outcome
measurement of the effect of septoplasty on nasal obstruction (24).

\textbf{Conclusion}

This study has shown a weak correlation between objective measurement of
nasal airflow and patient-reported evaluation of nasal breathing in
patients not selected according to symptoms of nasal obstruction or to
the level of nasal airflow. It has also been demonstrated that patients
with symptoms of nasal obstruction have different degrees of nasal
airflow, indicating that the sensation of nasal obstruction is not
solely determined by nasal airflow.

The findings of this study also suggest that a low nasal airflow
prevents the sensation of a good nasal breathing. According to this,
patients with symptoms of nasal obstruction and inappropriate nasal
airflow may require improving nasal airflow as an essential step towards
achieving an optimal functional result.

Conflict of Interests Declaration:

The Authors declare that they have no conflicts of interest

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Andre R, Vuyk H, Ahmed A, \emph{et al} . Correlation between
  subjective and objective evaluation of the nasal airway - a systematic
  review of the highest level of evidence. Clin Otolaryngol 2009;
  34(6):518--525
\item
  Barnes M, White P, Gardiner Q. Correlation between subjective and
  objective evaluation of the nasal airway. Clin Otolaryngol 2010;
  35(2):152--153
\item
  Eccles R, Doddi N, Leong S. Correlation Between Subjective And
  Objective Evaluation Of The Nasal Airway. Clin Otolaryngol 2010;
  35(2):149
\item
  Hopkins C. Correlation between subjective and objective evaluation of
  the nasal airway - a systematic review of the highest level of
  evidence. Clin Otolaryngol 2010; 35(2):147--148
\item
  Hopkins C, Earnshaw J, Roberts D. Correlation between subjective and
  objective evaluation of the nasal airway - a systematic review of the
  highest level of evidence. Clin Otolaryngol 2010; 35(4):337--338
\item
  Williams J, Kulendra K, Hanif J. Correlation between subjective and
  objective evaluation of the nasal airway - a systematic review of the
  highest level of evidence. Clin Otolaryngol 2010; 35(2):150--151
\item
  Nivatvongs W, Earnshaw J, Roberts D, \emph{et al} . Correlation
  between subjective and objective evaluation of the nasal airway - a
  systematic review of the highest level of evidence. Clin Otolaryngol
  2011; 36(2):181--182
\item
  Zhao K, Blacker K, Luo Y, Bryant B, Jiang J. Perceiving nasal patency
  through mucosal cooling rather than air temperature or nasal
  resistance. PLoS One 2011; 6(10):e24618
\item
  Jones A, Willat D, Durham L. Nasal airflow: resistance and sensation.
  Jour. Laryng. Otol. 1989; 10:909-911
\item
  Mohan S, Fuller J, Ford S, Lindsay R. Diagnostic and therapeutic
  management of nasal airway obstruction -advances in diagnosis and
  treatment. JAMA Facial Plast Surg. 2018; 20(5):409-418
\item
  Schumacher M, Pain M: Nasal Challenge Testing In Grass Pollen Hay
  Fever. J Allergy Clin Immunol 1979; 64:202--208
\item
  Welch M, Meltzer E, Orgel H, \emph{et al} . Assessment of the
  correlation of rhinometry with the symptoms and signs of allergic
  rhinitis in children. Ann Allergy 1985; 55:577--579
\item
  Vogt K, Jalowayski A, Althaus W, \emph{et al} . 4-Phase-Rhinomanometry
  - Basics and Practice 2010. Rhinol Suppl (21):1--50
\item
  Sipilä J, Suonpää J, Silvoniemi P, \emph{et al} . Correlations between
  subjective sensation of nasal patency and rhinomanometry in both
  unilateral and total nasal assessment. ORL J Otorhinolaryngol Relat
  Spec 1995; 57(5):260--263
\item
  Naito K, Kondo Y, Ohoka E, \emph{et al} . New aerodynamic aspects of
  nasal patency. Rhinology 1995; 33(1):26--29
\item
  Pastorello E, Riario-Sforza G, Incorvaia C, \emph{et al} . Comparison
  of rhinomanometry, symptom score, and inflammatory cell counts in
  assessing the nasal late-phase reaction to allergen challenge. J
  Allergy Clin Immunol 1994; 93(1):85--92
\item
  Naito K: Nasal patency: subjective and objective. Am J Rhinol 1989;
  3(2):93-97
\item
  Kumlien J, Schiratzki H. Methodological aspects of rhinomanometry.
  Rhinology 1979; 17(2):107-114
\item
  Watson W, Roberts J, Becker A, \emph{et al} . Nasal patency in
  children with allergic rhinitis: correlation of objective and
  subjective assessments. Ann Allergy Asthma Immunol. 1995;
  74(3):237-240
\item
  Hirschberg A,~Rezek O. Correlation between objective and subjective
  assessments of nasal patency. - ORL J. Otorhinolaryngol. Relat.
  Spec.1998; 60 (4); 206-211
\item
  Eccles R, Jones A. The effect of menthol on nasal resistance to air
  flow. J Laryngol Otol 1983; 97(8):705--709
\item
  Willatt D, Jones A. The role of the temperature of the nasal lining in
  the sensation of nasal patency. Clin Otolaryngol Allied Sci 1996;
  21(6):519--523
\item
  Sozansky J, Houser S. The physiological mechanism for sensing nasal
  airflow: a literature review. Int Forum Allergy Rhinol. 2014;
  4(10):834-838
\item
  Stewart M, Witsell D, Smith T \emph{et al} . Development and
  validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale.
  Otolaryngol Head Neck Surg 2004; 130(2):157-163
\item
  Ottaviano G, Lund V, Coles S, Staffieri A, Scadding G. Does peak nasal
  inspiratory flow relate to peak expiratory flow?. Rhinology 2008;
  46:200-203
\item
  Bezerra T, Padua F, Pilan R, Stewart M, Voegels R. Cross-cultural
  adaptation and~validation~of a quality of life questionnaire: the
  Nasal Obstruction Symptom Evaluation questionnaire. Rhinology~2011;
  49(2): 227-231
\item
  Taylor G, Macneil A, Freed D. Assessing degree of nasal patency by
  measuring peak expiratory flow rate through the nose. J Allergy Clin
  Immunol 1973; 52(4):193-198
\item
  Van Spronsen E, Ingels K, Jansen A \emph{et al} . Evidence-based
  recommendations regarding the differential diagnosis and assessment of
  nasal congestion: using the new GRADE System. Allergy 2008;
  63(7):820-833
\item
  R Core Team. R: A language and environment for statistical computing.
  Foundation for Statistical Computing, Vienna, 2019
\item
  RStudio Team (2018). RStudio: Integrated Development for R. RStudio
  Inc., Boston 2018
\item
  H. Wickham. ggplot2: Elegant Graphics for Data Analysis.
  Springer-Verlag, New York 2016
\item
  Swinscow T, Campbell M. Statistics at Square One, 10th Ed. London BMJ
  Books, 2002
\item
  Zubair M, Abdullah M, Ismail R \emph{et al} . Review: a critical
  overview of limitations of CFD modeling in nasal airflow. J. Med.
  Biol. Eng. 2012; 32:77-84
\item
  Segal R, Kepler G, Kimbell J. Effects of differences in nasal anatomy
  on airflow distribution: A comparison of four individuals at rest.
  Ann. Biomed. Eng. 2008; 36(11):1870--1882
\item
  Zao K, Jiang J. What is normal nasal airflow? A computational study of
  22 healthy adults. Int. Forum Allergy Rhinology 2014; 4:435-446
\item
  Tsubone H. Nasal 'flow' receptors of the rat. Resp Physiol 1989; 75:
  51-64
\item
  Jones A, Wight R, Durham L. The distribution of thermoreceptors within
  the nasal cavity. Clin Otolaryngol1989; 14(3): 235-239
\item
  Liu S, Lu H, Fan H, Wang H \emph{et al} . The identification of the
  TRPM8 channel on primary culture of human nasal epithelial cells and
  its response to cooling. Medicine 2017; 96:31e7640
\item
  Voets T, Owsianik G, Nilius B. Trpm8. Handb Exp Pharmacol 2007;
  (179):329--344
\item
  Bautista D, Siemens J, Glazer J \emph{et al} . The menthol receptor
  TRPM8 is the principal detector of environmental cold. Nature 2007;
  448(7150):204-208
\item
  Meusel T, Negoias S, Scheibe M, Hummel T. Topographical differences in
  distribution and responsiveness of trigeminal sensitivity within the
  human nasal mucosa. Pain 2010; 151(2):516-521.
\item
  Liu S, Lu H, Cheng L \emph{et al} . Identification of the cold
  receptor TRPM8 in the nasal mucosa. Am J Rhinol Allergy. 2015;
  29(4):112-116.
\item
  Sullivan C, Garcia G, Frank-Ito D, Kimbell J, Rhee J. Perception of
  better nasal patency correlates with increased mucosal cooling after
  surgery for nasal obstruction. Otolaryngol Head Neck Surg. 2014;
  150(1):139-147.
\item
  Bailey R, Casey K, Pawar S, Garcia G. Correlation of nasal mucosal
  temperature with subjective nasal patency in healthy individuals. JAMA
  Facial Plastic Surgery 2017; 19(1):46-52
\item
  Lindemann J, Keck T, Scheitauer M, Leiacker R, Wiesmiller K. Nasal
  mucosal temperature in relation to nasal airflow as measured by
  rhinomanometry. A. J. Rhinol. 2007; 21(1):46-49
\item
  Blomgren K, Simola M, Hytonen M, Pitkaranta A. Peak nasal inspiratory
  and expiratory flow measurements -- practical tools in primary care?.
  Rhinology 2003; 41:206-210
\item
  Starling-Schwanz R, Peake H, Salome C, Toelle B, Ng K, Marks G, Lean
  M, Rimmer S. Repeatability of peak nasal inspiratory flow measurements
  and utility for assessing severity of rhinitis. Allergy 2005;
  60:795-800
\item
  Ottaviano G, Scadding G, Coles S, Lund V. Peak nasal inspiratory flow.
  Normal range in adult population. Rhinology 2006; 44:32-35
\item
  Klossek J, Lebreton J, Delagranda A, Dufour X. PNIF measurement in a
  healthy French population. A prospective study about 234 patients.
  Rhinology 2009; 47:389-392
\end{enumerate}

\textbf{Tables}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& Coefficients Estimates & SE & p-value\tabularnewline
\midrule
\endhead
Intercept & 86.588 & 11.751 & \textless{}0.001\tabularnewline
NOSE - & 0.249 & 0.129 & 0.057\tabularnewline
Age & 0.457 & 0.274 & 0.099\tabularnewline
Sex (male) & 4.567 & 6.574 & 0.486\tabularnewline
\bottomrule
\end{longtable}

Table 1: Estimated regression coefficients, standard error (SE) and
p-values of a multiple linear regression model

\textbf{Legends of Figures}

Figure 1: Boxplot for the registered PNIF values (l/min) (Mean 92.6
l/min SD 28.1 l/min)

Figure 2: Boxplot for the registered NOSE scores

(Mean 48.4 SD 24.4)

Figure 3: Scatter plot and simple regression line of best fit together
with 95\% confidence bands between PNIF values and NOSE scores

Figure 4: Scatter plot and simple regression lines of best fit together
with 95\% confidence bands between PNIF and NOSE for each subgroup of
patients based on NOSE score

Figure 5: Scatter plot and simple regression lines of best fit together
with 95\% confidence bands between PNIF and NOSE for each subgroup of
patients based on PNIF value\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig/Fig}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fih/Fih}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fii/Fii}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fij/Fij}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fik/Fik}

\end{center}
\end{figure}

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

