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Nasal
Physiology and
Pathophysiology
ofNasal Disorders
ÖzlemÖnerciCelebi
T.MetinÖnerci
Editors
SecondEdition
123

Nasal Physiology and Pathophysiology
of Nasal Disorders

Özlem ÖnerciCelebi • T. Metin Önerci
Editors
Nasal Physiology and
Pathophysiology of
Nasal Disorders
Second Edition

Editors
Özlem ÖnerciCelebi
Department of Otoloaryngology Head
and Neck Surgery
University of Health Sciences, Istanbul
Training and Research Hospital
Istanbul, Turkey
T. Metin Önerci
Faculty of Medicine
Hacettepe University
Ankara, Turkey
ISBN 978-3-031-12385-6 ISBN 978-3-031-12386-3 (eBook)
https://doi.org/10.1007/978-3-031-12386-3
© Springer Nature Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher,
whether the whole or part of the material is concerned, specically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms or in any
other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specic statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To our teachers whom we owe all our knowledge and the way
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to think scientically, to our colleagues who shared their
experience and inspire us to learn, to our students who inspire
us to teach.

Preface
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It is with great pleasure that we present the second enlarged edition of the
book Nasal Physiology and Pathophysiology of Nasal Disorders. The rst
edition was accepted with great enthusiasm and received very good feedback.
It was sold out. Since its online publication on 2013, there have been more
than 99,000 downloads for the eBook on SpringerLink and it was among the
top most downloaded eBooks in its respective eBook Collection in 2019.
There is so much new information that we felt the need to make a second
edition.
The diseases can be better understood and managed if we know the pathophysiology of the diseases. This is very closely related to the changes in the
physiology. The progress only can be made by studying the physiology and
pathophysiology of the diseases. The great interest for this book is perhaps
due to the wish of our colleagues to learn more and more on this topic.
We want to thank the distinguished authors of this book who are experts in
their elds and gave their valuable time to prepare their chapters with the
recent information. We tried to cover all aspects of nasal physiology and
pathophysiology.
We hope that the second edition with its new, enlarged and updated chapters will ll the gap on this topic.
Istanbul, Turkey ÖzlemÖnerci Celebi
Ankara, Turkey T.MetinÖnerci
August, 2021
vii

Contents
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1 Mucus, Goblet Cell, Submucosal Gland . . . . . . . . . . . . . . . . . . . . 1
Takeshi Shimizu
2 The Coagulation System and Rhinosinusitis . . . . . . . . . . . . . . . . 15
Takeshi Shimizu and Shino Shimizu
3 Cilia, Ciliary Movement, and Mucociliary Transport . . . . . . . . . 29
Mark Jorissen and Martine Jaspers
4 Functional Defense Mechanisms of the Nasal Respiratory
Epithelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Robert C. Kern and Jennifer R. Decker
5 Local B-Cell and T-Cell Populations in the Pathophysiology
of Chronic Rhinosinusitis with Nasal Polyposis . . . . . . . . . . . . . . 61
Kent K. Lam and Amber U. Luong
6 Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Hirohisa Saito
7 Macrophage and Mast Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Hideyuki Kawauchi
8 The Neutrophil and Chronic Rhinosinusitis . . . . . . . . . . . . . . . . . 91
Martin Y. Desrosiers and Shaun J. Kilty
9 Eosinophils in Rhinologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . 97
Jens Ponikau, Mary Twarog, David Sherris, and Hirohito Kita
10 Biologic Therapies for Chronic Rhinosinusitis . . . . . . . . . . . . . . . 115
Michael J. Aw and Shaun J. Kilty
11 Nasal NO and Its Role in the Physiology of the Nose
and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Peter W. Hellings and Glenis K. Scadding
12 Physiology and Pathophysiology of Sneezing and Itching:
Mechanisms of the Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Murat Songu and T. Metin Onerci
13 The Dry Nose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Rainer K. Weber, Tanja Hildenbrand, Detlef Brehmer,
and Jochen A. Werner
ix

x
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14 Physiology of the Aging Nose and Geriatric Rhinitis . . . . . . . . . 157
Yazan Eliyan, Victoria E. Varga-Huettner,
and Jayant M. Pinto
15 Nutrition and the Upper Respiratory Tract . . . . . . . . . . . . . . . . . 179
Jim Bartley
16 Physiology of Lacrimal Drainage . . . . . . . . . . . . . . . . . . . . . . . . . 185
Ali Riza Cenk Çelebi and Özlem Önerci Celebi
17 Intranasal Trigeminal Perception . . . . . . . . . . . . . . . . . . . . . . . . . 193
Philippe Rombaux, Caroline Huart, Basile Landis,
and Thomas Hummel
18 Sinus Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Jim Bartley
19 Computational Fluid Dynamics of the Nasal Cavity . . . . . . . . . . 215
Ralph Mösges
20 Physiology and Pathophysiology of Nasal Breathing . . . . . . . . . . 225
Achim G. Beule, Giorgi Gogniashvili, and Gunter H. Mlynski
21 Function of the Turbinates: Nasal Cycle . . . . . . . . . . . . . . . . . . . . 245
Achim G. Beule and Rainer K. Weber
Contents
22 Nasal Physiology and Pathophysiology and Their
Relationship with Surgery: The Nasal Valves. . . . . . . . . . . . . . . . 255
Oren Friedman and Kevin Wang
23 Nose and Sleep Breathing Disorders . . . . . . . . . . . . . . . . . . . . . . . 269
Anne-Lise Poirrier, Philippe Eloy, and Philippe Rombaux
24 Pathophysiology of Obstructive Sleep Apnea . . . . . . . . . . . . . . . . 289
Kivanc Gunhan
25 Rhinomanometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Zeynep Onerci Altunay
26 Acoustic Rhinometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Evren Hizal and Ozcan Cakmak
27 New Measurement Methods in the Diagnostic
of Nasal Obstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Gunter H. Mlynski, Giorgi Gogniashvili, and Achim G. Beule
28 Testing of Transport and Measurement of Ciliary Activity . . . . 363
Mark Jorissen and Martine Jaspers
29 Nasal Defensive Proteins: Distribution and
a Biological Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
Hideyuki Kawauchi
30 Olfaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Huart Caroline, Philippe Eloy, and Philippe Rombaux

Contents
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xi
31 Olfactory Impairement in Disease and Aging . . . . . . . . . . . . . . . 403
Ayşe Elif Özdener-Poyraz and Mehmet Hakan Özdener
32 Electron Microscopy and the Nose . . . . . . . . . . . . . . . . . . . . . . . . 419
Mürvet Hayran
33 Genetic Background of the Rhinologic Diseases . . . . . . . . . . . . . 437
Mehmet Gunduz, Eyyup Uctepe, and Esra Gunduz
34 Vomeronasal Organ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Cemal Cingi, Aytuğ Altundağ, and İsmail Koçak
35 Physiology of the Nasal Cartilages and Their
Importance to Rhinosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
Wolfgang Pirsig
36 Physiology and Pathophysiology of the Growing
Nasal Skeleton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
H. L. Verwoerd-Verhoef, G. J. V. M. van Osch,
and C. D. A. Verwoerd
37 Physiologic Concerns During Rhinoplasty . . . . . . . . . . . . . . . . . . 531
E. B. Kern
38 Nasal Pulmonary Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
Jim Bartley
39 Physiologic and Dentofacial Effects of Mouth Breathing
Compared to Nasal Breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Tulin Taner and Banu Saglam-Aydinatay
40 The Nose and the Eustachian Tube . . . . . . . . . . . . . . . . . . . . . . . . 581
Özlem Önerci Celebi
41 Nanomedicine and the Nose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
Gürer G. Budak✠, Cengiz S. Ozkan, Mihrimah Ozkan,
and T. Metin Önerci

Mucus, Goblet Cell, Submucosal
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Gland
TakeshiShimizu
1
Abbreviations
AP-1 Activated protein-1
AR Allergic rhinitis
AZM Azithromycin
CAM Clarithromycin
CF Cystic brosis
CREB cAMP response element-binding protein
CRS Chronic rhinosinusitis
cysLTs Cysteinyl leukotrienes
EGFR Epidermal growth factor receptor
EM Erythromycin
Foxa2 Forkhead box a2
IL Interleukin
NF-κB Nuclear factor κ-B
RA Retinoic acid
STAT6 Signal transducer and activator of tran-
scription 6
TGF Transforming growth factor
TLR Toll-like receptor
TNF Tumor necrosis factor
Core Messages
Airway mucus is important for the host defense
mechanism, acting as a physicochemical barrier
T. Shimizu (*)
Department of Otorhinolaryngology-Head and Neck
Surgery, Shiga University of Medical Science, Otsu,
Shiga, Japan
e-mail: shimizu@belle.shiga-med.ac.jp
to protect the underlying epithelium from pathogens and particles. The major components of
mucus are glycoproteins called mucins, which
are secreted by epithelial goblet and submucosal
gland cells. Mucins are large heterogeneous
macromolecules containing hundreds of oligosaccharide chains attached to peptide backbones,
which are encoded by several MUC genes.
Hypersecretion of mucus is commonly observed
in various sinonasal inammatory conditions
such as acute rhinitis, chronic rhinosinusitis, and
allergic rhinitis. Mucus hypersecretion, leading
to rhinorrhea, contributes signicantly to the
pathophysiology of these diseases by impairing
mucociliary function, resulting in stagnation of
pathological mucus that contains various inammatory mediators and pathogenic microbes.
1.1 Introduction
Airway mucus blankets all mucosal surfaces,
providing a physicochemical barrier that protects
the underlying epithelium against bacteria,
viruses, and inhaled particles and gases. Mucus
maintains airway hydration and plays an important role in the innate immune system by trapping
foreign and endogenous substances, facilitating
clearance by mucociliary activity. Mucus also
has antioxidant, antiprotease, and antimicrobial
functions. Composed of water, ions, serum protein exudates, epithelial secretions, and glandular
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
Ö. Ö. Celebi, T. M. Önerci (eds.), Nasal Physiology and Pathophysiology of Nasal Disorders,
https://doi.org/10.1007/978-3-031-12386-3_1
1
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