Laboratory diagnosis 1997-otolaryngology---head-and-neck-surgery

1. Laboratorydiagnosis
BERRYLINJ. FERGUSON,MD,and RICHARDL. MABRY,MD,Pittsburgh, Pennsylvania, and Dallas, Texas
Laboratory studies are performed to confirm or
exclude the presence of a suspected disorder or to
obtain additional information about that disorder. This
section critically reviews the tools that are available to
objectively measure nasal function including patency,
olfaction, and mucociliary transport (Table 1). Also
reviewed are the laboratory tests that are used to diag-
nose sinonasal disorders including allergy, immunode-
ficiency, mucociliary transport abnormalities, genetic
disorders, autoimmune diseases, and disorders of
unknown cause that constitute distinct pathologic enti-
ties (Table 2). Because imaging studies, nasal
endoscopy, and microbiologic cultures are covered
elsewhere in this publication, they are alluded to only
briefly in this section.
NASAL FUNCTION STUDIES
Nasal Patency
Rhinomanometry. Also called nonacoustic rhi-
nometry, rhinomanometry was the first technique
introduced to objectively measure nasal patency.
Rhinomanometry measures transnasal pressure and
airflow simultaneously. With simultaneous measure-
ment of pressure and flow, transnasal resistance may
be calculated with Ohm's law.
The International Committee on Standardization of
Rhinomanometry has recommended that nasal patency
be expressed as resistance (the ratio of transnasal pres-
sure to flow of respiratory air in a patient breathing
exclusively through the nose, expressed in centimeters
of water per liter per second or in pascals per cubic cen-
timeter per second).t The graph of pressure versus flow
is a sigmoid curve (Fig. 1).
Fromthe Departmentof Otolaryngology(Dr.Ferguson),University
of Pittsburgh School of Medicine, and the Department of
Otorhinolaryngology (Dr. Mabry), The University of Texas,
SouthwesternMedicalSchoolat Dallas.
Reprint requests: Berrylin J. Ferguson, MD, the Departmentof
Otolaryngology,UniversityofPittsburghSchoolofMedicine,The
Eye and Ear Institute Building, Suite 500, 200 Lothrop St.,
Pittsburgh,PA15213.
OtolaryngolHeadNeckSurg1997;117:$12-$26.
Copyright© 1997 by the AmericanAcademyof Otolaryngology-
Headand NeckSurgeryFoundation,Inc.
0194-5998/97/$5.00 + 0 23/0/83512
$12
Toble 1. Tools commonly used for the objective
measurement of nasal function
Nasal patency
Acoustic rhinometry
Rhinomanometry
Mucociliary transport
Saccharine method
Radiolabeledor radiopaque tracers
Olfaction
Universityof PennsylvaniaSmell IdentificationTest
(UPSIT)
Various methods can be used to measure both
transnasal pressure and transnasal airflow. Methods of
measuring transnasal pressure can be combined with
any of the methods of transnasal airflow measurement.
The three methods of transnasal pressure measurement
are as follows:
1. Anteriorly, at the nostril, while the patient breathes
exclusively through the contralateral nostril. This
method cannot be used in patients with total uni-
lateral nasal obstruction or septal perforation.2
2. Posteriorly, with a tube in the oropharynx between
the tongue and the palate. The patient may breathe
through both nostrils simultaneously with this
method.
3. Postnasally, with a pediatric feeding tube placed
along the floor of the nasal cavity and into the
nasopharynx. With this method the patient may
breathe through both nostrils simultaneously.
Transnasal airflow is measured by a pneumota-
chometer (a resistor that induces laminar flow across it
so that the pressure drop varies linearly) and a pressure
transducer (an instrument that measures the differential
pneumotachometer pressure). Pressure calibration is
accomplished with a water manometer. The pneumota-
chometer may be attached or connected in one of sev-
eral ways:
1. A nozzle inserted into the nasal vestibule. This has
the disadvantage of distorting the nasal valve.
2. A face mask. This may distort the facial tissues.
Furthermore different types of face masks result in
different resistance measurements. Although real-
positioning of the mask can result in errors, nasal
distortion is less than with the nozzle measurement

2. Otolaryngology-
Head and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSON and MABRY $13
Table 2. Laboratory tests for the diagnosis of sinonasal disorders
Diagnosis
=
Allergic rhinitis
Allergic fungal
sinusitis (AFS)
Autoimmune disorders
Wegener's
granulomatosis
Polyarteritis nodosa
Relapsing
polychondritis
Cerebrospinal fluid
rhinorrhea
Cystic fibrosis
Disorders of unknown
cause
Sarcoidosis
Churg-Strauss
syndrome
Immunodeficiency
Mucociliary transport
abnormalities
Primary ciliary
dyskinesia
(Kartagener's
syndrome)
Neoplasm
Malignant
neoplasms
Lethal midline
granuloma
(angiocentric T-cell
lymphoma)
Benign neoplasms
Gold standard
Skin testing (prick or
intradermal) or in vitro
measurement of specific
immunoglobulin (Ig) E
Mucin histopathology
Fungal cultures of mucin
Nasal biopsy
Nasal biopsy
Nasal biopsy
I]-2
Transferrin
Sweat test
Nasal biopsy (diagnosis
of exclusion--negative
cultures for fungus and
acid-fast bacilli)
Nasal biopsy (vasculitis
is not usually seen in
nasal specimens); must
be coupled with clinical
picture and ung biopsy
Documentation of absence
of function of a subset of
the immune ~ystem
Electron microscopy of
nasal cilia
Ciliary beat function
studies
Nasal biopsy
Nasal biopsy
Nasal biopsy
Helpful or
suggested
screening tests
Nasal cytology
Total IgE
IgE and IgG to
specific fungus
Cytoplasmic antineutrophil
cytoplasmic antibody
assay (c-ANCA)
Erythrocyte sedimentation
rate
Perinuclear antineutrophil
cytoplasmic antibody
assay (p-ANCA)
Glucose of fluid
Sweat patch test
Sweat conductivity
Angiotensin
converting enzyme
level
Chest radiograph
Complete blood count
with differential
(eosinophil count)
Total IgG
IgM, IgA, IgG
subclasses
Complete blood
count with differential
CH50 or CH100
Mucociliary transport
test (saccharine
or thallium)
Epstein-Barr virus titers
if nasopharyngeal
carcinoma is suspected
Serum electrophoresis if
plasmocytoma is
suspected
Possiblyhelpful or
secondary tests
Erythrocyte
sedimentation rate
Complete blood count
Nasal action potential
Genetic tests
Erythrocyte
sedimentation
rate
Kveim test
tgG1 deficiency: response
to diphtheria and
tetanus toxoid vaccine
IgG2 deficiency: response
to pneumococcal
vaccine

3. $14 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
~hinomanomatr~ Report
Itnnic: laight:
~ge:
Z..3~ T CALCUlaTED :
TZST ~3tZSSUILE: -1.50 c= 120
SeXI
LZPT R~GIT
~e~sUrement Pre Post Pre Post
Resistance (c= I20/L/sec) 6.02 4.45 6.75 5.27
~roms (c~ }{20/L/sec) 5.99 4.40 6.72 5.24
conductance (cc/s/cm ~20) 166.07 224.91 14g.15 189.72
~low (cc/ssc) 249.11 337.36 222.22 284.59
~OTH ~OSTRILS
~re Post
Work of ~reathing 2.96 I.~6
I~B = ~ress~ra Out of Bounds
TOTIL
3.1~ ~.41
u/~ ~/~
~.2~ ~x.~
471.34 621.~5
l~re C h ~ l l e r ~ 3 e U ~ l u e ~
0.8
: : i ,
t ! ! i ' i " -'. !
o.s---L-U ! ! . . . . . .
llli ""'~
• i " " ;
I i i i i ~ ~.1--
"I O . O - ! ! I ! ! ! i_l
v - - r--T--~.---~ - ' -r-T-~ n - -
! - ! I
~_-o.3_ ~ l--i
!
" " ".- I
I ! i i ,, i i ill
I .~ ! I ', ~. ! i I
-o.e - i - I i ~ '
- - 3 . 0 - - I , 8 ~ 0 . 6 0 . 6 1 . 8 3 . 0
P r e . ~ u ~ e { c ~ }4:IND)
- - - L~ft N o s t r i l
- - R i g h t N o ~ t r i l
Te=t done by
Po~t Challeng~ U~lu~
0.8
iil
• ! ~. .
iii U-~'''~
i I |
O.3- ', l t . r - - - . - - ~ ~
iii ,
' " /iiii
o.o---f-T-]-- , "-~- i- "--
1 i l ! | :
-o. ~ -r-T-T-
I ii ,
_o.8/:1: I
--3.0 --1,8 --0.6 0 o6 I .I@ 3.0
Fig. 1. Sample computerized rhinomanometry report.
distortion is less than with the nozzle measurement
technique of airflow,a
3. Body plethysmography. The face is unrestricted,
and results are consistent and reproducible.
However, the apparatus is bulky, and considerable
patient cooperation is required. 3
Commercially available rhinomanometry units are
now computerized (MultiSPIRO, Inc., Irvine, Calif.),
and they have disposable probes and masks. These units
have real-time graphic data displays that allow easy
detection of air leaks and other artifacts that can
adversely affect reproducibility or accuracy. Testing
can be completed in 2 minutes.
Acoustic rhinometry. This modality, which was
introduced in 1989,4 assesses the geometry of the nasal
cavity by analyzing reflected sound waves. Two mea-
surements are commonly obtained. One is the minimal
cross-sectional area, and the other is the nasal volume.
Occasionally, a total minimal cross-sectional area is
calculated by adding the right and left minimal cross-
sectional areas. This has the theoretic advantage of
negating some of the variation caused by cyclic
turbinate engorgement.

4. Otolaryngology-
Head and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSON and MABRY S15
Analysis Segment: 3.00 to 6.00
Req(cmH20/i/m) Volume(cm^3) Min Area(cm^2) at Length(cm)
I. left : 0.353 5.75 0.95 3.06
2. right : 0.951 .2.88 0.83 4.99
4. left : 0.000 0.00 0.00 5.95
3. right : 0.000 0.00 0.00 5.95
2. mig~% / New Da~a ~--
4i?~?g~.!~.i?~.i~.~?}..!~?!!!!!i?i?!?!}!!!?!!ii!!??!i?!???!i!!!!??i~ii!??~ii!!??~!!?!?~!!ii~?!~!!i!?i??
~"~Na~'a"1"?"'?a'J;v e"~
......"......g
......i.....:.!......i......~
......i......i......i......i .....- .....~.....- ....
• ::~:.q::::~:.~::.::.7:::::.::::::.::::::.:::~:~.:..~::...::.~::r..~..~..".:~...f~:~:~:::~i
:ili::~ii'''=-.i~ii@
illi~?ii~
0 . ......."
:!"!'"!......~ : ~ ~ .
......-......?..,....:.:_ ~':"
......'.{ i i ~ ~
.......- . .-':--.
v :I..0 :::::::::::::::::::::::::::::::::::::::::: :::~:::::" ==============================================
:::::::::::::::::::::::::::::::::::::::::::::::::::::
i'" ==============================================================
........ ~."i ...... ":...... ".''",'{ ...... =.'"r"=. ...... '....... ":...... "" ..... " ...... ":...... "....... < ...... ~:...... "........ :.....
....: i......??i ......? ? i <! ......i......i......i......i......i......t ......t .....t .....t ....
...... i-,~.~i ...... {i...... {---:-{ ...... {...... ".-...... { ..... • ...... " ...... ".-...... {...... {....... ::....... i....... '....... ! .....
..... i ...... i...... !<i ...... i...... i...... !...... i...... i...... i...... i...... i...... !....... i....... i ......i...... i.....
o.o~ ......... I ......... 1......... I.......... I..... m'rl-rr ....... 1......... I......... I'' 'rrrrr
-6.0 -4.0 -2.0 0.0 2.0 4.0 6,0 8.0 10.0 1
Distanoe.(cm).
Fig. 2. Computerized acoustic rhinometry graph for right and left sides of nose. Segment ana-
lyzed for volume can be adjusted. Computerized version can display right and left, before
and after, in four different colors for visualization (Hood Laboratories, Pembroke, Mass.).
Acoustic rhinometry is now computerized and com-
mercially available (Hood Laboratories., Pembroke,
Mass.), and the assessment can be performed with ease
in less than 1 minute. Because acoustic rhinometry
demonstrates the cross-sectional area on the vertical
axis and the distance from the front of the nose on the
horizontal axis, areas of constriction are easily local-
ized (Fig. 2).
Sources of error include improper positioning of the
nozzle or patient breathing during assessment. The nozzle
of the commercially available acoustic rhinometry units
can distort and dilate the nasal valve area. ff improperly
applied, the nozzle may fail to accurately reflect constric-
tion in the nasal valve area. Chin or forehead supports
have recently been added to the acoustic rhinometry stand
in an effort to improve the reproducibility of findings,
particularly at the nasal valve area.5 Patients should be
instructed to hold their breath (for approximately 15 sec-
onds) while undergoing testing.6
The reported average minimal cross-sectional area is
0.62 cm 2 at 2.35 cm from the nostril. With decongestant
sprays the minima1 cross-sectional area moves forward
to 2.00 cm from the nostril but increases to only 0.67
cm2.7 Patients with severe septal deflections and a feel-
ing of almost total occlusion have a minimal cross-sec-
tional area of approximately 0.3 cm2. In one study8
patients who were dissatisfied with the outcome of sep-
tal surgery to correct obstruction had an average mini-
mal cross-sectional area of 0.45 cm2, whereas those
who were satisfied with surgical outcome had an aver-
age minimal cross-sectional area of 0.74 cm2.
Comparison of rhinomanometry and acoustic
rhinometry.Although acoustic rhinometry is generally
more accurate and reproducible, rhinomanometry may
be superior in certain situations including those in
which volume or minimal cross-sectional area must be
calculated beyond a severe constriction.9
In their initial description of acoustic rhinometry,
Hilberg et al.4 demonstrated that this technique was
more accurate and reproducible than three other assess-

5. $16 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
ments of nasal anatomy: nonacoustic rhinometry (ante-
rior rhinomanometry with a face mask), area measure-
ments obtained by computed tomographic (CT) scan-
ning, and area measurements obtained by a water dis-
placement method. The assessments were performed in
a variety of settings including cadavers, normal sub-
jects, nasal cast models, and patients with nasal cavity
obstructions. The study results showed that the areas
measured by acoustic rhinometry were more accurate
than those obtained by nonacoustic rhinometry and
were more highly correlated with the areas measured by
CT scanning (r --- 0.94) or the water displacement
method (r = 0.96). Acoustic rhinometry had a coeffi-
cient of variation of <2% compared with 15% for nona-
coustic rhinometry.
Rhinomanometry and acoustic rhinometry may be
complementary tests in inhalation challenge studies,
because different correlations with nasal congestion
under baseline and challenge conditions can be demon-
strated with different test groups. 1° Unlike rhino-
manometry, acoustic rhinometry does not require flow
through the nose for measurement; thus it can be used
when the nose is totally occluded. With the commer-
cially available units measurements can be obtained in
less than 1 minute with acoustic rhinometry compared
with approximately 2 minutes with nonacoustic rhi-
nometry.
Objective measurements of nasal patency do not
always correlate with a patient's subjective sensation of
nasal congestion. 11-13When a patient reports nasal con-
gestion and has normal objective measurements, abnor-
malities at the nasal valve area and in the region of the
middle turbinate should be specifically evaluated by
anterior rhinoscopy and endoscopic examination. In
children nasal obstruction is frequently not a subjective
complaint, despite objective evidence to the contrary.14
Acoustic rhinometry is not recommended as a test for
monitoring the recurrence of tumors of the nasal cavi-
ty.15
Mucociliary Transport
Normal, coordinated ciliary activity is required to
transport mucus toward the nasopharynx, thereby pro-
tecting the upper airway. Abnormalities in either the
mucus or the function of the cilia can have a variety of
causes. Most of these abnormalities are transient, and
they are associated with various viral and bacterial
infections16-21 or exposures to allergens or environ-
mental pollutants such as cigarette smoke.22 More
problematic are the nontransient, frequently genetic
causes of mucociliary transport dysfunction. These
include primary ciliary dyskinesia (in which ciliary
anatomy or function is abnormal) and cystic fibrosis (in
which ciliary anatomy and function are normal but the
mucus is abnormally thick).
To assess mucociliary transport, a number of soluble
and insoluble tracers have been applied to some part of
the nasal mucosa. Care must be taken to place any trac-
er at or posterior to the most anterior 1 to 2 cm of the
nasal mucosa, because this section of the nasal cavity
directs mucociliary transport anteriorly and not posteri-
orly.
Soluble tracers. A soluble tracer, which presumably
dissolves in the mucus, may be a visible dye (e.g., food
coloring), an agent that can be tasted by the subject
(e.g., saccharine), or a combination of both. It is
hypothesized that soluble tracers are transported simi-
larly to topically applied drugs or water-soluble inhaled
gases.
The saccharine method is the safest and most wide-
ly used soluble tracer test. In this test a small amount of
saccharine powder is placed on the medial aspect of the
inferior turbinate 1 to 2 cm behind the leading edge.
The patient is instructed to avoid sniffing or blowing
the nose and is instructed to swallow frequently. The
transport time is the time from the application of the
saccharine powder to the time at which the patient
detects a sweet saccharine taste. The saccharine particle
method time is normally 5 to 8 minutes; 12 minutes is
slow, and more than 25 minutes indicates a mucociliary
transport disorder.23 The saccharine test measures the
fastest transport time.24 A time lapse is required
between repeat tests to allow the sweetness to disap-
pear.
If a dye is used as the tracer, the oropharynx must be
examined every minute or so. Alternatively, endoscop-
ic nasal techniques may be used as long as the anatom-
ic end point of dye transport is specified.
Insoluble tracers. Tests with insoluble tracers prob-
ably mimic the transport of substances stuck in the
thick gel mucus. Examples of these markers include
insoluble dyes and small, visible particles such as char-
coal powder, colloidal sulphur, or 600-Hm aluminum
disks. Radiopaque or radioactively tagged human
serum albumin particles or Teflon disks provide an
assessment of clearance in the entire nasal cavity.
However, these tests subject patients to a small radia-
tion exposure. The nasal transit time by insoluble trac-
er methods averages approximately 6 minutes.25
Summary of soluble and insoluble tracer mea-
surements of mucociliary transport, The saccharine
method is the most widely used, because it is easy,
inexpensive, and safe. This method measures the fastest
transport time, not the total transport time. It reflects the

6. Otolaryngology-
Head and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSONand MABRY S17
solubility of the marker in mucus, in contradistinction
to insoluble markers or tagged radioactive particles.
The saccharine test correlates well with measurements
with the use of two of the insoluble markers: radioac-
tively tagged resin particles and 600-~lm aluminum
disks.26
A daily variation ranging from 43% to 74% is noted
with all mucociliary transport studies. The least varia-
tion is seen with the saccharine test, and the most vari-
ation is with radioactively tagged resin particles.26
A delay in mucociliary transport time can suggest
the need for an evaluation of known causes of mucocil-
iary transport dysfunction. A normal mucociliary trans-
port time excludes the diagnosis of primary ciliary
dyskinesia.
Adjunctive Evaluation of Suspected
Mucociliary Dysfunction: Ciliary Beat Function
Studies and Ultrastructural Analysis
When nasal mucociliary clearance studies indicate
that an abnormality is present, appropriate tests may
include ciliary beat frequency and orientation analysis
with photometric techniques or ultrastructural assess-
ment with electron microscopy. With both of these
studies a san~ple of cilia must be obtained by biopsy or
by scraping the inferior turbinate with a nasal brush or
a small mechanical scraper specifically designed to
obtain turbinate epithelium (Rhinoprobe, Apotex
Scientific Inc., Arlington, Tex.). The tests are comple-
mentary.
Variants of primary ciliary dyskinesia have been
described in which the ultrastructure and the ciliary
beat frequency were normal and only the ciliary beat
orientation was abnormal.27 Primary ciliary dyskinesia
is the preferred term for congenital abnormalities of cil-
iary activity including Kartagener's syndrome. The
clinical presentation begins at birth, usually with per-
sistent rhinosinusitis, otitis media, pulmonary infec-
tions, and frequently bronchiectasis.
The initial screening examination should be an eval-
uation of nasal mucociliary clearance. The identifica-
tion of abnormal cilia must be interpreted within the
clinical context, because up to 10% of cilia are struc-
turally abnormal in patients with normal mucociliary
transport times and no nasal pathologic condition or
symptoms.
Disorders known to cause reversible delays in
mucociliary function such as infection and exposure to
noxious agents should be treated appropriately. Only if
treatment fails and mucociliary transport continues to
be delayed should ultrastructural or ciliary function
tests be considered.2s,29 Patients with mucociliary
transport dysfunction caused by infection may respond
to correction of ostiomeatal complex obstruction or
other anatomic deformity by endoscopic sinus surgery.
At present, there is no treatment to correct primary
ciliary dyskinesia. When a patient has absent nasal
mucociliary clearance, it is important to consider the
cost-effectiveness of pursuing ultrastructural analysis
and ciliary beat function tests to make a diagnosis for
which there is no therapeutic intervention. It seems rea-
sonable to assume that a patient with mucociliary trans-
port dysfunction caused by an irreversible ciliary disor-
der (documented by electron microscopy or family his-
tory combined with ciliary beat function studies) would
be less likely to improve after endoscopic sinus surgery
than would a patient with a reversible mucociliary
transport disorder.
Endoscopic sinus surgery or external approaches
may be required in both irreversible and reversible
causes of mucociliary transport disorders. The decision
to operate or reoperate on a patient with a documented
irreversible ciliary disorder should be directed at
removing infection and allowing wide drainage of the
sinuses, not toward restoring function to the sinuses.
However, there are no controlled studies to support this
approach.
Olfaction
Smell identification. The most popular olfacto~
test is smell identification by multiple choice of 40
odorants activated by scratching microencapsulated
material with a pencil. The patient's score on the test is
compared with norms standardized for age and sex.
The most widely used tool is the Smell Identification
Test (Sensonics, Inc., Haddon Heights, N.J.). The com-
mercial test packet includes booklets of microencapsu-
lated odors and an administration and scoring manual.
Sometimes this test is referred to as the University of
Pennsylvania Smell Identification Test.3° A patient's
score falls into one of four categories: normal for age
and sex, micro-osmic, anosmic, or probably malinger-
ing. On a 40-item multiple choice test involving four
choices per item, a patient should identify approxi-
mately 10 items correctly by chance alone. Patients
who miss 35 or more items are probably malinger-
ing.
A shorter (12-item) screening version of the
University of Pennsylvania Smell Identification 40-
item test is also available (Sensonics, Inc.).
Threshold testing.Odor detection threshold tests
have received a great deal of clinical attention. The con-
centration of a stimulus is increased (or decreased)
incrementally until the stimulus is barely perceived.

7. $18 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
The stimuli concentrations, usually in log-step concen-
tration, are presented in "sniff' or squeeze bottles.
Threshold tests require a considerable amount of
administration time, because multiple presentations are
required to determine a reliable detection threshold.
Consequently, only one or two odorants are usually
tested. Phenyl ethyl alcohol, which has a roselike smell
and produces little trigeminal reactivity, is commonly
used. Most patients who are insensitive to one chemical
are also insensitive to other chemicals. However,
patients with "smell blindness" in which only a small
number of stimuli are involved have been reported.31
For this reason it is recommended that odor identifica-
tion tests be used in addition to threshold tests.32
Olfactory biopsy. A hook-shaped instrument (Storz
Instrument Co., St. Louis, Mo.) can be used to perform
olfactory neuroepithelial biopsy with endoscopy in the
office without any objective adverse effect on the sense
of smell. Specimens obtained in this way are free of
crush artifact and thus are suitable for ultrastructural
analysis. More studies are required to determine the
correlation of histopathologic and clinical findings, and
the use of this technique is currently restricted to
research centers.33,34
Disorders of olfaction may be associated with
endocrine, neurologic, psychiatric, and nutritional dis-
orders. Appropriate specific laboratory testing is
required to identify any of these disorders. A lengthy
list of these conditions has been well reviewed by
Schiffman35 and by Dory et al.36
LABORATORY TESTSFOR DIAGNOSING
SINONASAL DISORDERS
Allergic Rhinitis
Conflicting data exist regarding the incidence of
allergy with rhinosinusitis. Before endoscopic sinus
surgery was introduced, Friedman37 reported that aller-
gy was present in 94% of patients with hyperplastic
chronic sinusitis who were treated with sinus surgery.
In more recent articles on sinus surgery outcomes in
which the presence of allergy was investigated, the inci-
dence of allergy has ranged from 14%38 to more than
60%.39 Most articles report that approximately 50% of
patients with chronic sinusitis who require endoscopic
sinus surgery probably have both allergy and rhinosi-
nusitis.4°,41 Parsons and Phillips42 found that allergy
was present in 60% of children requiring endoscopic
sinus surgery, whereas Lazar et al.43 noted allergy in
49% of 260 children treated with sinus surgery.
It is appropriate to perform at least a screening test
for inhalant allergy in patients with chronic or recurrent
sinusitis. A previously published clinical practice
guideline of the American Academy of Otolaryngic
Allergy covered the subject of allergy testing in depth
and is considered authoritative in this area.44
Allergy testing may be performed by either a skin
test (prick or intradermal) or by in vitro means includ-
ing radioallergosorbent testing and enzymatic-marker
variants such as the enzyme-linked immunosorbent
assay. Both skin and in vitro tests accurately and repro-
ducibly detect allergen-specific immunoglobulin E
(IgE), and both correlate well with the clinical signs
and symptoms elicited by antigen exposure.45 A cost-
effective screening test with 12 to 15 antigens is an
excellent predictor of the presence of significant
inhalant allergy46 and may be the basis for successful
initial immunotherapy.47 However, additional antigens
may subsequently be tested depending on the individual
situation.
Laboratory diagnostic aids in allergic fungal
sinusitis. Allergy is present in all patients with allergic
fungal sinusitis. Patients with this type of sinusitis are
distinguished from other atopic patients by clinical pre-
sentation and histologic, laboratory, and radiographic
findings. These patients typically have elevated total
IgE levels, and they demonstrate atopy (by either skin
tests or a radioallergosorbent test) to both fungal and
nonfungal antigens.48,49 Other diagnostic tests that
have been suggested include the total eosinophil count
and, if available, fungal antigen-specific immunoglob-
ulin G (IgG) and precipitating antibodies.5°
Clinical and radiologic findings often suggest the
presence of allergic fungal sinusitis before surgery, but
the diagnosis is confirmed by histopathologic examina-
tion of the tenacious allergic mucin found in the sinus-
es. The histopathologic features include a dense
eosinophilic infiltrate, Charcot-Leyden crystals, and
noninvasive fungal hyphae.51,52 Special fungal stains
are usually required to identify the hyphae on histolog-
ic section. Fungal cultures may or may not be positive.
Nasal Cytology
The importance of examining smears of nasal secre-
tions to differentiate allergic and infectious rhinosinusi-
tis was emphasized many years ago by Hansel.53Based
on his experience with 10,000 specimens from 1000
allergic patients over a 12-year period, Hansel reported
that nasal eosinophilia was strongly associated with
allergy, whereas neutrophils were associated with
infection. Bryan and Bryan54 coined the term
"cytogram" to describe the mixture of epithelial and
goblet cells, leukocytes, and mast cells in nasal secre-
tions and, along with others,55 believed that they could
distinguish allergy, bacterial infection, viral infection,
and vasomotor rhinitis from such an examination. No
recent investigators have shown a similar expertise.

8. Otolaryngology-
Heod and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSONand MABRY $|9
Initial methods of cytologic examination involved
secretion collection by blowing the nose into waxed
paper or by the use of a cotton swab. However, use of
the Rhinoprobe can increase the accuracy of nasal cyto-
logic examination.56,57
The presence of eosinophils in nasal secretions has
been said to indicate the presence of allergy,58-6°
whereas neutrophils are more indicative of an infec-
tious cause.61-6~However, the administration of topical
nasal corticosteroids may significantly reduce the pres-
ence of eosinophils in the nose,6t so that patients who
are receiving these medications may not show nasal
eosinophilia. Furthermore eosinophils may be present
in the secretions of patients with nonallergic rhinitis.64
Thus althongh nasal smears remain a helpful adjunctive
tool in differentiating allergic from infectious rhinosi-
nusitis, other more specific tests may be more useful
and definitive.
Nasal and Sinus Cultures
The relative inaccessibility of the sinus cavities
makes it difficult to obtain specimens for bacteriologic
cultures. The standard in this area has been puncture of
the maxillary antrum, which is the approach required
by the U.S. Food and Drag Administralion for drug
studies dealing with rhinosinusitis. In clinical practice,
however, this sampling technique generally is not nec-
essary for the treatment of community-acquired infec-
tions unless patients do not respond to empiric thera-
py.65 Antral aspiration may also be considered in
patients with suspected nosocomial rhinosinusitis66 or
serious complications of rhinosinusitis. 67,6sEven if cul-
tures are negative, the act of puncturing and lavaging
the maxillary antrum may be therapeutic.69
Considerable interest has been shown in obtaining
cultures directly from the middle meatus under fiberop-
tic endoscopic guidance.7° Although only anecdotal
data on the efficacy of this method are currently avail-
able, it remains a more appropriate choice than nasal
culture. When sinus cultures are required, they should
be incubated appropriately and then examined for aero-
bic and anaerobic organisms. For determination of their
true significance, culture results must be correlated
with clinical findings.
Based on the findings in a study of samples obtained
with endoscopy from the middle meatus with the use of
a small calcium alginate swab on a flexible metal shaft,
Klossek et al.71 have suggested that this area,contains a
commensal flora that represents the bacteria found in
the maxillary ,antrum. These same authors are perform-
ing additional studies to match culture results from
antral lavage and middle meatus samples obtained with
endoscopy. Once they have completed their work, fur-
Table .3. Clinical situations in which immunodefi-
ciency should be suspected
A patient with recurrent acute infections (more than four
infections per year) who clears completely between
episodes when treated with antibiotics but requires antibi-
otics to clear and in whom there is no evidence of an
anatomic abnormality causing sinus obstruction
A patient with recurrent infections in whom there is no evi-
dence of a mucociliary defect or an anatomic obstruction
(often, an evaluation for immunodeficiency is undertaken
after the patient fails to improve after endoscopic sinus
surgery and the elimination of a suspected anatomic con-
striction)
A patient who has a persistent infection that does not
respond to adequate antibiotic therapy or who has
repeated relapses after adequate antibiotic therapy
A patient with infections at other sites (especially meningi-
tis, sepsis, pneumonia)
A patient wkh unusual pathogens or severe infections (e.g.,
Pneumocystis carinii, severe varicella infection with pneu-
monia or hepatitis, infection from an attenuated virus)
A patient with a family history of immunodeficiency
ther light may be shed on the utility of this sampling
technique.71
immunodeficiency
Although allergy, repeated exposure to upper respi-
ratory infections (e.g., in day care workers), and
anatomic obstruction are the most common causes of
persistent or recurrent infectious sinusitis, immunodefi-
ciency must be considered when other causes have been
excluded. Clinical situations in which immunodeficien-
cy should be suspected are presented in Table 3.
There is no standard "immunologic work-up." No
one test or limited group of tests adequately evaluates
all of the more than 50 known immunodeficiency dis-
orders. For the purpose of evaluation, immunodeficien-
cies can be grouped into five functional groups: anti-
body deficiencies, T-cell defects, combined immune
deficiencies (antibody and T-cell deficiencies), comple-
ment deficiencies, and phagocytic cell dysfunctions.
The type of infection directs the immunologic
work-up (Table 4).72 Patients with antibody deficien-
cies have primarily recurrent or persistent bacterial
infections with encapsulated gram-positive and some
gram-negative organisms. Fungal, viral, and protozoal
infections are absent or rare in these patients, although
infections with Pneumocystis and Giardia species may
occur. Patients with T-cell defects have fnngal, viral;
and protozoal infections, but they rarely have bacterial
infections. Patients with complement deficiencies have
a more narrow range of infections, and they are partic-
ularly susceptible to gram-negativejnfections. Chronic
granulomatous disease, a dysfunction of phagocytosis,

9. S20 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
Table 4. Correlation of type of infection with the form of immunodeficiency
Type of infection
Immunodeficiency Bacterial Viral Fungal Protozoan
Antibody deficiency +++ + - +
T-cell deficiency - +++ +++ +++
T-cell/B-cell deficiency +++ +++ +++ +++
Complement deficiency +++ - - -
Phagocytic dysfunction +++ - ++ -
+++, Strongcorrelation;++, correlation;+, slight correlation;-, no correlation.
Adaptedfrom PoimarSH. Approachto the child withimmunedeficiency.Curt ViewsAllergy Immuno11994;22:1-11.Usedwithpermission.
Table 5, Laboratory evaluation based on the suspected form of immunodeficiency*
Antibody deficiency
Quantitation of serum immunoglobulin (Ig): IgG, IgA, IgM, IgE, and IgG subclasses
Measurement of antibodies from previous immunization or infection: diphtheria, tetanus, rubella, rubeola,
influenza, varicella
Measurement of preimmunization and postimmunization antibody titers: pneumococcal poiysaccharide
vaccine, Haemophilusinfluenzaetype B vaccine, diphtheria toxoid, tetanus toxeid
T-Lymphocyte deficiency or dysfunction
Complete blood count with differential
Delayed hypersensitivity skin tests: Candida, tetanus toxoid, diphtheria toxoid, Streptococcus and Proteus
extracts
T-lymphocyte population and subpopulation counts
In vitro lymphocyte stimulation tests
Complement deficiency (OH100 or OH50)
Serum total hemolytic complement activity (CH50)
If positive CH50 abnormality: C3, C4, alternative pathway hemolytic activity assay, circulating immune complexes
Phagocytic dysfunction
Complete blood count with morphologic examination of leukocytes
Nitroblue tetrazolium dye reduction test
Measurement of leukocyte adhesion molecules (LFA-1 and Mac-1/CR3)
*SeeTable4.
Adaptedfrom PolmarSH. Approachto the childwithimmunedeficiency.CurrViewsAllergy Immuno11994;22:1-11.Usedwithpermission.
is characterized by recurrent abscesses and infections
with catalase-positive bacteria such as Staphylococcus
aureus or gram-negative bacteria. Another disorder of
phagocytic function is a leukocyte adhesion deficien-
cy. Immunofluorescence tests and flow cytometry are
required to measure the expression of integrins, LFA-1
and Mac-1/CR3, on leukocytes. Thus the type of
infection helps guide the examination of the portion of
the immune system that is most likely to be defec-
tive.72, 73
An immunodeficiency disorder may be present in as
many as 50% of adult patients with recurrent acute or
persistent sinusitis.74,75 The most common causes of
immunodeficiency associated with chronic recurrent
sinusitis are immunoglobulin deficiencies including
IgG subclass deficiencies. Once an abnormally low
immunoglobulin level is demonstrated, functional tests
(e.g., responses to immunization) are required. A mar-
ginally low level of an immunoglobulin or an
immunoglobulin subset with a normal functional
response to antigen exposure is not considered patho-
logic. Occasionally, patients have normal levels of all
immunoglobulins but demonstrate an absent or strik-
ingly low level of functional response.74
T-cell abnormalities are less common than
immunoglobulin defects. The most frequent T-cell
abnormality is the one seen in patients infected with the
human immunodeficiency virus. Sinusitis and abnor-
mal sinus radiographs are common in patients with the
acquired immunodeficiency syndrome. In such patients
therapy should be directed at the symptoms.
The laboratory evaluation for patients with recurrent
bacterial infections or suspected immunodeficiency is
outlined in Table 5.72 The finding of unusual pathogens
(i.e., fungi or parasites) supports the need for laboratory
testing of T-cell function. Because T cells constitute
approximately 70% of the lymphocytic population, a
complete blood count with differential should be
obtained before the immunologic work-up moves to
specific T-cell counts. Because of the prevalence of
human immunodeficiency virus infection and its associ-
ation with sinusitis and unusual pathogens, a human

10. Otolaryngology-
Head and Neck Surgery
Volume ] 17 Number 3 Part 2 FERGUSONand MABRY S21
immunodeficiency virus test should be considered in all
patients for whom an immunologic work-up is consid-
ered.
The most abundant immunoglobulin is [gG. Normal
serum concentrations for total IgG range from 800 to
1800 mg/dl (8.00 to 18.00 gm/L). There ,are four sub-
classes of IgG.
1.The IgG1 subclass is responsible ~or antibody
responses to bacterial protein antigens such as
tetanus toxoid and diphtheria. Of the total IgG,
67% is IgG1. If a deficiency of IgG1 is identified,
a functional assessment of antibody titers should
be performed before and after the administration of
tetanus or diphtheria toxoid.
2. The IgG2 subclass constitutes 20% to 25% of the
total IgG and is primarily responsible for antibod-
ies directed against polysaccharide capsules such
as Haemophilus influenzae and Streptococcus
pneumoniae. 76 Functional assessment is ascer-
tained by immunization with pneumococcal vac-
cine. A pneumococcal titer obtained 130 days after
pneumococcal vaccination should show a twofold
to fourfold increase in antibody titers over prevac-
cination levels.77
3.The IgG3 subclass is important in the primary
response to viral illness and against Moraxella
(Branhamella) catarrhalis and the M component
of Streptococcus pyogenes. A deficiency of IgG3 is
reported to be the most common subclass deficien-
cy in adults.78
4.Approximately 15% of the population has IgG4
levels that are not detectable by current assay tech-
niques. The significance of an IgG4 deficiency
remains unclear.78
The incidence of IgA deficiency is 1 case per 600 to
800 in the general population. The predominant
immunoglobulin class on mucosal surfaces is IgA. It is
not uncommon to see patients with low IgA levels who
have no clinical symptoms. Patients with symptomatic
IgA deficiency often have a coexisting [gG subclass
deficiency or an autoimmune disorder.74
Serologic Markers
Serologic markers may be helpful in diagnosing sev-
eral sinonasal disorders. Although a definitive diagno-
sis almost ,always requires a biopsy to demonstrate
characteristic histopathologic features, ancillary sero-
logic tests can be useful in directing the work-up.
The erythrocyte sedimentation rate is; elevated in
many autoimmune, infectious, idiopathic, and even
neoplastic disorders. The erythrocyte sedimentation
rate is a very inexpensive test that measures the dis-
tance red blood cells fall in 1 hour when they are sus-
pended in a vertical tube. A sedimentation rate may be
useful in following the course of a chronic autoimmune
disorder. Although the presence of a normal sedimenta-
tion rate does not eliminate an autoimmune disorder, it
makes the diagnosis less likely.
Sarcoidosis: Angiotensin-converting enzyme.
The cause of sarcoidosis is unknown. Head and neck
involvement is present in 9% of patients with this dis-
order, and isolated nasal manifestations may be present
in 1% of affected individuals. 79
Although most patients with sarcoidosis show some
depression of immunologic function including anergy
to skin testing, decreased T-cell function, and elevated
IgA and IgG levels, these findings are nonspecific.
Thus biopsy and histopathologic examination of suspi-
cious areas of the nose should be performed. Biopsies
of the minor salivary glands from the lower lip have
also been used to diagnose sarcoidosis.8° However, the
diagnosis of this condition requires the exclusion of
other disorders that are associated with the histopatho-
logic finding of noncaseating granuloma.
High levels of angiotensin-converting enzyme are
found in 60% to 100% of patients with active sarcoido-
sis.79,81-83 These levels return to normal (44 to t25
nmol/ml/min) after steroid therapy.82 The mechanism
of the elevations is unknown.
The Kveim test for sarcoidosis is accurate in 80% to
85% of cases and has a false-negative rate of 2%. 84
However, this test is seldom done now because of con-
cern about bloodborne pathogen transmission and
because a commercial test is not available.85 The
Kveim test involves intradermal injection of an antigen
extract from a patient with known sarcoidosis. The test
is considered positive if a nodule develops at the injec-
tion site within 4 to 8 weeks and there is histopatholog-
ic evidence of a noncaseating granuloma in the nodule.
No definitive diagnostic test for sarcoidosis is avail-
able. The basic work-up includes a history, a physical
examination, biopsy of suspicious lesions (i.e., lesions
demonstrating noncaseating granuloma), negative cul-
tures for fungus and acid-fast bacilli, angiotensin-con-
verting enzyme levels, a chest radiograph, and skin
tests.
Wegener's granulomatosis: Anf~ineutrophil cyto-
plasmic antibody. The diagnosis of Wegener's granu-
lomatosis is based on clinical and pathologic findings.
Classically, this disease is characterized by the
histopathologic finding of necrotizing granulomas and
focal necrotizing vasculitis of the upper and lower res-
piratory tracts associated with focal necrotizing
glomerulonephritis. Because the histopathologic triad
of vasculitis, necrosis, and granulomatous inflamma-

11. $22 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
tion is reported to occur in only 26% to 42% of patients,
the histopathologic findings must be integrated with the
serologic laboratory findings and the clinical presenta-
tion.86
Wegener's granulomatosis often begins as a local-
ized process, with more than 90% of patients initially
experiencing head and neck symptoms.8vMost of these
symptoms are chronic rhinitis and nasal airway obstruc-
tion (71%), purulent sinusitis (47%), and epistaxis (less
than 20%). 88 If Wegener's granulomatosis is diagnosed
early (e.g., while it is localized to the nose) and treat-
ment is instituted, the patient may never progress to
lower respiratory or renal involvement. If left untreated,
Wegener's granulomatosis usually progresses to fatal
systemic disease, with a mean survival of 5 months and
a mortality rate of 90% at 2 years.89
In addition to biopsy of the afflicted area (lung,
sinus, or nose), ancillary laboratory assays can be help-
ful in diagnosing Wegener's granulomatosis. Probably
the most important ancillary assay is the cytoplasmic
antineutrophil cytoplasmic antibody (c-ANCA) assay.
When positive, this test results in a characteristic cyto-
plasmic staining pattern produced by autoantibodies.
The target antigen responsible for c-ANCA is a serine
proteinase (proteinase-3). The c-ANCA assay is highly
specific for Wegener's granulomatosis (98%).9o The
sensitivity of the assay varies with the status of the dis-
ease. During active generalized disease the assay is
95% sensitive, during active limited disease it is 67%
sensitive, and during inactive disease it is only 32%
sensitive.91
False-positive c-ANCA results have been reported in
patients with a number of infectious and neoplastic dis-
orders. Thus a positive c-ANCA assay does not obviate
the need for tissue diagnosis in a patient with clinical
manifestations suggestive of Wegener's granulomato-
sis, especially if signs of glomerulonephritis are lack-
ing.92 Likewise, a negative c-ANCA assay does not
necessarily rule out the diagnosis of Wegener's granu-
lomatosis, and histopathologic confirmation is impor-
tant.
The c-ANCA level can also be used to follow dis-
ease activity. Increased c-ANCA levels are present 1 to
2 years before clinical exacerbations in half of patients
who relapse. 89'93 However, many patients with
Wegener's granulomatosis in remission continue to
have high c-ANCA titers for years.9~
A positive perinuclear ANCA (p-ANCA) assay is
found in other forms of systemic vascnlitis and
glomerulonephritis. Thus the p-ANCA assay is not as
specific for Wegener's granulomatosis as the c-ANCA
assay. Additional laboratory findings in Wegener's
granulomatosis include an elevated erythrocyte sedi-
mentation rate, normochromic or normocytic anemia,
and thrombocytosis.
Cystic Fibrosis
Cystic fibrosis (CF) is common, occurring in one of
every 2750 live births. The frequency and severity of
the clinical manifestations and complications of this
disease vary greatly. The sweat test is the gold standard
for the diagnosis of CE 94 The following clinical sce-
narios are indications for a sweat test in a child or ado-
lescent: nasal polyps,95,96recurrent or chronic sinusitis
that is refractory to antimicrobial therapy,97 and isola-
tion of the mucoid variant of Pseudomonas aeruginosa
from a respiratory tract culture.9s
In approximately 5% to 10% of cases the diagnosis
of CF is made in adolescence or adulthood. 99 The pos-
sibility of this disease should be considered in every
child or adolescent regardless of race and apparent
health who fails to respond as anticipated to therapy for
rhinosinusitis. The diagnosis of CF will be missed if the
sweat test is not done correctly or if the test is not
repeated in a patient with a highly suggestive clinical
picture and a negative or borderline sweat test.94
Sweat test. This test must be performed by experi-
enced personnel with good quality control. The two test
methods that have been approved by the U.S. Cystic
Fibrosis Foundation are the Gibson-Cooke proce-
dure 1°° and the Macroduct Sweat Collection System
(Westcor, Inc., Logan, Utah). 1°1 In both systems local-
ized sweating is stimulated by iontophoresis of pilo-
carpine into the skin of the flexor surface of the fore-
arm, calf, or thigh with an electrical charge of 5 mV for
5 to 10 minutes.
The Gibson-Cooke method collects sweat on filter
paper or gauze, whereas the Macroduct System collects
it in microbore tubing. The amount of sweat is quanti-
fied, and the sample is analyzed for chloride or sodium
concentrations. It is essential that the sample be
obtained from only one site. Pooled samples from sev-
eral sites or sweat from the head, trunk, or areas of dif-
fuse inflammation or serous or bloody discharge give
erroneous results.
Both false-positive and false-negative sweat tests
can occur. Furthermore sweat test values can vary
depending on the method of sweat stimulation, salt
intake, sweat secretory rate, and nutritional hydration
status. Conditions that can cause elevated sweat test
values include untreated adrenal insufficiency, anorex-
ia nervosa, untreated hypothyroidism, and hypogam-
maglobulinemia. There have been reports of negative
sweat tests in patients with CE Genetic testing can be
helpful in these cases. 102
Sweat testing may not be feasible until 4 weeks of

12. Otolaryngology-
Head and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSON and MABRY S23
age because of the difficulty in collecting an adequate
sweat sample.94 The diagnosis of CF requires two pos-
itive sweat tests or one elevated sweat test and the iden-
tification of two CF mutations.
Potential difference measurement. The increased
sodium absorption and decreased chloride permeability
in CF result in a higher maximum transepithelial volt-
age, or potential difference, across nasal epithelium.
Amiloride, a sodium transport inhibitor, accentuates
this reduction of voltage. The in vivo measurement of
voltage across the nasal epithelium, coupled with the
response to amiloride and isoproterenol (a ~3-adrenergic
agonist), can be used to differentiate patients with CF
(including those with borderline or even normal sweat
test results) from patients with other disorders. 1°3-1°5
Potential difference measurement is available only at a
limited number of medical centers; however, its diag-
nostic utility is widely confirmed, and it should be con-
sidered a useful procedure in ambiguous clinical situa-
tions.94
Screening tests. The sweat patch test collects
sweat, stimulated by pilocarpine iontopheresis, with a
paper patch that changes color if the chloride concen-
tration is greater than 45 mmol/L. This is only a screen-
ing procedure, and it should not be used for the defini-
tive diagnosis of CE
The nonselective measurement of ions with a con-
ductivity analyzer (Wescor Sweat-Chek, Logan, Utah)
has been approved as a screening method by the Cystic
Fibrosis Foundation. A sweat conductivity result equal
to or greater than 50 mmol/L (equivalent sodium chlo-
ride) is positive and should be followed by a quantita-
tive sweat test.94
Genetic testing.CF is caused by mutations in the
CF transmembrane conduction and regulator gene.
These mutations lead to abnormal function of the chlo-
ride channel More than 550 mutations have been iden-
tified. In the white population of North America,
approximately 70% of CF chromosomes have the
AF508 mutation. 1°6 Nasal polyposis is more common
in patients who are homozygous for the AF508 muta-
tion. 1°7 Thirteen mutations occur with a frequency of
1% or greater and account for 87% of CF alleles. The
frequency of mutations varies greatly from one popula-
tion to another. A screen for 31 CF mutations is avail-
able as a blood test.
Genetic testing may be recommended when the
patient and physician do not have easy access to an
experienced sweat test laboratory or when cystic fibro-
sis is strongly suspected but the sweat test has been neg-
ative. The genetic diversity of patients with CF is great,
and patients with unusual mutations may still have CF
even in the presence of a negative screening genetic test.
In the patient with clinical features consistent with
CF, the identification of two CF mutations confirms the
diagnosis. The identification of a CF mutation on one
allele does not confirm the diagnosis, but it does
increase the likelihood that the patient has a variant
form of CF, providing useful information for genetic
counseling.
Mutation analysis is seldom helpful in patients with
atypical clinical features or borderline sweat test
results, because these individuals often do not carry the
mutations present in diagnostic screening panels. In
addition, CF should not be diagnosed in the patient who
has two CF mutations but does not have a consistent
clinical picture. CF is a clinical, not a genetic, diagno-
sis.
ALTERNATIVES TO RADIOGRAPHIC IMAGING OF
THE PARANASAL SINUSES
Transiliumination
For more than 50 years transillumination has been
used to obtain clues about the presence of retained
secretions or significant mucosal thickening in the
frontal or maxillary sinuses (but in no other sinuses)] °8
Although a series comparing antral and frontal transil-
lumination with sinus radiographs ~°9 showed 100%
concordance between normal radiographs and transillu-
mination, only 55% of patients with positive radi-
ographic findings had abnormal transillumination.
With transillumination, intraobserver reproducibility
is low in assessing the maxillary sinuses (60%) but high
in assessing the frontal sinuses (90%).11° At times trans-
illumination may be a helpful adjunct, but it should not
be the sole basis for making a treatment decision.
Ultrasound Scans
A-mode ultrasound scans can demonstrate the pres-
ence of fluid or tissue filling a sinus. However, if air is
present between the anterior sinus wall and the patho-
logic sinus content, the ultrasound impulse will be
absorbed, and a false-negative ("normal") pattern wilt
result.I°9,111
Like transillumination, ultrasound scans are limited
in their application to the diagnosis of frontal or astral
disease. In a comparison of ultrasound scans and sinus
radiographs that used CT scans as a reference, Hl ultra-
sound scanning was found to be more sensitive but less
specific than radiographs in diagnosing maxillary sinus
disease.
A-mode ultrasound scanning may be valuable in fol-
lowing the course of maxillary sinusitis once a positive
diagnosis has been established, because ultrasound
examination does not subject a patient to radiation
exposure or antral puncture. 112

13. $24 FERGUSON and MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
REFERENCES
1. Clement PAR. Committee report on standardization of rhino-
manometry. Rhinology 1984;22:151-5. (grade A)
2. McCaffrey TV. Rhinomanometry and vasoactive drugs affecting
nasal patency. In: Getcheli TV, Doty FL, Bartoshuk LM, et al.,
editors. SmelI and taste in health and disease. New York: Raven
Press, 1991:chap 31. (grade C)
3. Lai VW, Corey JR The objective assessment of nasal patency.
Ear Nose Throat J 1993;72:395-400. (grade C)
4. Hilberg O, Jackson AC, Swift DL, et al. Acoustic rhinometry:
evaluation of nasal cavity geometry by acoustic reflection. J
Appl Physiol 1989;66:295-303. (grade A)
5. Fisher EW, Boreham AB. Improving the reproducibility of
acoustic rhinometry: a customized stand giving control of height
and angle. J Laryngol Otol 1995;109:536-7. (grade C)
6. Tomkinson A, Eccles R. Errors arising in cross-sectional area
estimation by acoustic rhinometry produced by breathing during
measurement. Rhinology 1995;3:238-240. (grade B)
7. Roithman R, Cole P, Chapnik J, et al. Acoustic rhinometry in the
evaluation of nasa1obstruction. Laryngoscope 1995;105:275-81.
(grade B)
8. Grymer LF, Hilberg O, Elbrond O, et al. Acoustic rhinometry:
evaluation of the nasal cavity with septal deviations, before and
after septoplasty. Laryngoscope 1989;99:1180-7. (grade B)
9. Tomkinson A, Eccles R. The identification of the potential limi-
tations of acoustic rhinometry using computer-generated, three-
dimensional reconstructions of simple models. Am J Rhinol
1996;10:77-82. (grade A)
10. Kesavanathan J, Swift DL, Fitzgerald TK, et al. Evaluation of
acoustic rhinometry and posterior rhinomanometry as tools for
inhalation challenge studies. J Toxicol Environ Health
1996;28:48:295-307. (grade C)
11. Huygen PLM, Klaassen AMB, DeLeeuw TJJ, et al.
Rhinomanometric detection rate of rhinoscopically assessed
septal deviations. Rhinology t 992;30:177-81. (grade B)
12. Sipila JI, Suonpaa JT, Laippala PT. Sensation of nasal obstruc-
tion compared to rhinomanometry in patients referred for septo-
plasty and in patients with chronic rhinitis. Am J Rhinol
1994;8:113-6. (grade B)
13. Roitbmann R, Cole E Chapnik J, et al. Acoustic rhinometry, rhi-
nomanometry, and the sensation of nasal patency: a correlative
study. J Otolaryngol 1994;23:454-8. (grade B)
14. Watson WTA, Roberts JR, Beker AB, et al. Nasal patency in
children with allergic rhinitis: correlation of objective and sub-
jective assessments. Ann Allergy 1995;74:237-40. (grade B)
15. Lender H, Pentz S, Brunner M, et al. Follow-up of patients with
inverted papilloma of the nasal cavities: computer tomography,
video-endoscopy, acoustic rhinometry. Rhinology 1994;32:167-
72. (grade B)
16. Denny E Effect of a toxin produced by Haemophilusinfluenzae
on ciliated respiratory epithelium. J Infect Dis 1974;129:93-100.
(grade C)
17. Ferguson JL, McCaffrey TV, Kern EB, et al. The effects of sinus
bacteria on human ciliated nasal epithelium in vitro. Otolaryngol
Head Neck Surg 1988;98:299-304. (grade C)
18. Mylotte JM, Stack RR, Murphy TF, et al. Functional and ultra-
structural effects of nontypable Haemophilus influenzae in a
hamster trachea organ culture system. In Vitro Cell Dev Biol
Anita 1985;21:575-82. (grade C)
19. Wilson R, Roberts D, Cole R Effect of bacterial products on
human ciliary functionin vitro. Thorax 1985;40:125-31. (grade C)
20. Hingley ST, Hastie AT, Kueppers F, et al. Effect of cilia factors
from Pseudomonasaeruginosaon rabbit respiratory cilia. Infect
Immun 1986;51:254-62. (grade B)
21: Sykes DA, Wilson R, Greenstone M, et aL Deleterious effects of
purulent sputum sol on human ciliary function in vitro: at least
two factors identified. Thorax 1987;42:256-61. (grade B)
22. Waguespack R. Mucociliary clearance patterns following endo-
scopic sinus surgery. Laryngoscope 1995;105:1-40. (grade B)
23. Grossan M. Mucociliary flow in otolaryngology practice.
Insights Otolaryngol 1993;8:1-7. (grade C)
24. Passali D, Bellussi L, Bianchini Ciampoli M, et al. Experiences
in the determination of nasal mucociliary transport time. Acta
Otolaryngol (Stockh) 1984;597:319-23. (grade B)
25. Englender M, Chamovitz D, Harell M. Nasal transit time in nor-
mal subjects and pathologic conditions. Otolaryngol Head Neck
Surg 1990;103:909-12. (grade A)
26. Puchell E, Aug E Fpham QT, et al. Comparison of three meth-
ods for measuring nasal mucociliary in man. Acta Otolaryngol
(Stockh) 1981;191:297-303. (grade A)
27. Rayner CFJ, Rutman A, Dewar A, et aL Ciliary disorientation
alone as a cause of primary ciliary dyskinesia syndrome. Am J
Respir Crit Care Med 1996;153:1123-9. (grade C)
28. Rayner CFJ, Rutman A, Cole PJ, et al. Ciliary disorientation in
patients with chronic upper respiratory tract infection. Am J
Respir Crit Care Med 1995;151:800-4. (grade C)
29. Carson JL, Collier AN, Chinn-Chin S, et al. Acquired ciliary
defects in nasal epithelium of children with acute viral upper res-
piratory tract infection. N Engl J Med 1985;312:463-8. (grade C)
30. Dory RL, Shaman P, Dann MS. Development of the University
of Pennsylvania Smell Identification Test: a standardized
microencapsulated test of olfactory function. Physiol Behav
1984;32:489-502. (grade A)
31. Amoore JE. Specific anosmias. In: Getchell TV, Doty FL,
Bartoshuk LM, et al., editors. Smell and taste in health and dis-
ease. New York: Raven Press, 1991:chap 41. (grade C)
32. Snow JB, Doty RL, Bartoshuk LM. Clinical evaluation of olfac-
tory and gustatory disorders. In: Getchell TV, Doty FL,
Bartoshuk LM, et al., editors. Smell and taste in health and dis-
ease. New York: Raven Press, 1991:chap 27. (grade C)
33. Lanza DC, Moran DT, Doty RL, et al. Endoscopic human olfac-
tory biopsy technique: a preliminary report. Laryngoscope
1993;103:815-20. (grade C)
34. Lanza DC. The effect of human olfactory biopsy on olfaction: a
preliminary report. Laryngoscope 1994;104:837-40. (grade B)
35. Schiffman SS. Taste and smell in disease. N Engl J Med
1983;308:1275-9, 1337-43. (grade C)
36. Doty RL, BartoshukLM, Snow JB. Causes of olfactory and gus-
tatory disorders. In: Getchell TV, Doty FL, Bartoshuk LM, et al.,
editors. Smell and taste in health and disease. New York: Raven
Press, 1991:chap 26. (grade C)
37. Friedman WH. Surgery for chronic hyperplastic rhinosinusitis.
Laryngoscope 1975;85:1999-2011. (grade C)
38. Schaitkin B, May M, ShapiroA, et al. Endoscopic sinus surgery:
4-year follow-up on the first 100 patients. Laryngoscope
1993;103:1117-20. (grade C)
39. Hoffman SR, Mahoney MC, Chmiel JF, et al. Symptom relief
after endoscopic sinus surgery: an outcomes-based study. Ear
Nose Throat J 1993;72:413-20. (grade B)
40. Benninger M. Rhinitis, sinusitis, and their relationships to aller-
gies. Am J Rhinol 1992;6:37-43. (grade B)
41. Kennedy DW. Prognostic factors, outcomes and staging endo-
scopic sinus surgery. Laryngoscope 1992;102(Suppl 57):1-18.
(grade B)
42. Parsons DS, Phillips SE. Functional endoscopic surgery in chil-
dren: a retrospective analysis of results. Laryngoscope
1993;103:899-903. (grade B)
43. Lazar RH, Younis RT, Long TE. Functional endonasal sinus
surgery in adults and children. Laryngoscope 1993;103:1-5.
(grade C)
44. Fornadley JA, Corey JR Osguthorpe JD, et al. Allergic rhinitis:
clinical practice guideline. Otolaryngol Head Neck Surg
1996;115:115-22. (grade A)
45. American Academy of Allergy and Immunology. Skin testing
and radioallergosorbent testing (RAST) for diagnosis of specif-
ic allergens responsible for IgE-mediated diseased. Position
statement 10. Milwaukee: American Academy of Allergy and
Immunology, 1983. (grade A)
46. King WK. Efficacy of a screening radioallergosorbenttest. Arch
Otolaryngol 1982;108:781-6. (grade B)
47. Lehr A, Mabry RL, Mabry C. The screening RAST: is it a valid
test? Otolaryngol Head Neck Surg 1997;117:54-5. (grade C)

14. Otolaryngology-
Head and Neck Surgery
Volume 117 Number 3 Part 2 FERGUSONand MABRY $25
48. Manning SC, Mabry RL, Schaefer SD, et al. Evidence of IgE-
mediated hypersensitivity in allergic fungal sinusitis.
Laryngoscope 1992;103:717-21. (grade B)
49. Mabry RL, Manning SC. Radioallergosorbent microscreen and
total immunoglobulin E in allergic fungal sinusitis. Otolaryngol
Head Neck Surg 1995;113:721-3. (grade C)
50. Corey JR Delsupehe KG, Ferguson BJ. Allergic fungal sinusitis:
allergic, infectious, or both? Otolaryngol Head Neck Surg
1995;113:110-9. (grade C)
51. Bent JP II~, Kuhn FA. Diagnosis of allergic fimgal sinusitis.
Otolaryngol Head Neck Surg 1994;111:580-5. (grade C)
52. Morpeth JF, Rupp NT, Dolen WK, et al. Fungal sinusitis: an
update. Ann Allergy Asthma Immunol 1996;76:128-40. (grade
C)
53. Hansel FK. The cytology of the secretions in allergy of the nose
and pmanasal sinuses. In: Hansel FK, editor. Allergy of the nose
and paranasal sinuses. St Louis: Mosby, 1936:375-83. (grade B)
54. Bryan MD, Bryan WTK. Cytologic diagnosis irLallergic disor-
ders. Otolaryngol Clin North Am 1974;7:637-66. (grade B)
55. Bickr0ore .IT, Marshall ML. Cytology of nasal secretions: fur-
ther diagnostic help. Laryngoscope 1976;86:516-23. (grade C)
56. Meltzer EO, Orgel HA, Jalowayski AA. Histaraine levels and
nasal cytology in children with chronic otitis media and rhinitis.
Ann Allergy Asthma Immunol 1995;74:406-10. (grade B)
57. Jong CN, Olson NY, Nadel GL, et al. Use of nasal cytology in
the diagnosis of occult chronic sinusitis in asthmatic children.
Ann Allergy 1994;73:509-14. (grade B)
58. Holopainen E. Nasal cytology as a nasal test. Rhinology
1976;14:29-356. (grade C)
59. Mygind N, Dirksen A, Johnson NJ, et al, Perennial rhinitis: an
analysis of skin testing, serum IgE, and blood and smear
eosinophilia in 201 patients. Clin Otolaryngol 1978;3:189-96.
(grade A)
60. Bhandari CM, Baldwa VS. Relative value of peripheral blood,
secretion and tissue eosinophilia in the diagnc,sis of different
patterns of allergic rhinitis. Ann Allergy 1976;37:280-4. (grade
B)
61. Meltzer EO, Orgel HA, Bush RK, et al. Evaluation of symptom
relief, nasal airflow, nasal cytology, and acceptability of two for-
mulations of fiunisolide nasal spray in patients with perennial
allergic rhinitis. Ann Allergy 1990;64:536-40. (grade B)
62. Savolainen S, Ylikoski J, Jousirnies-Somer H. Differential diag-
nosis of purulent and non-purulent acute maxillary sinusitis in
young adults. Rhinology 1989;27:53-61. (grade B)
63. Shapiro GG, Virant FS. Chronic sinus disease: medical manage-
ment in children. Immunol Allergy Clin North Am 1994;14:47-
68. (grade C)
64. Mullarkey MF, Hill .IS,Well DR. Allergic and nonallergic rhini-
tis: their characterization with attention to the meaning of nasal
eosinophils. J Allergy Clin Immunol 1980;63:122-6. (grade B)
65. Winter B, Gwaltney JM Jr, Therapeutic approach to sinusitis:
antiinfectious therapy as the baseline of management.
Otolaryngol Head Neck Surg 1990;103:876-8. (N'ade C)
66. Bert 15, Lambert-Zechovsky N. Microbiology of nosocomial
sinusitis in intensive care unit patients. J Infect 1995;31:5-8.
(grade B)
67. Gwaltney JM Jr, Sydnor A Jr.. Sands MA. Etiology and antimi-
crobial treatment of acute sinusitis. Ann Otol Rhinol Laryngol
1981;90(Suppl):68-71. (grade C)
68. Benjamin B. Sinusitis in children--general cop.sideration. Int J
Pediatr Otorhinolaryngol 1983;5:281-4. (grade C)
69. Goldenhersh MJ, Rachelefsky GS, Dudley J, et al. The microbi-
ology of chronic sinus disease in children with respiratory aller-
gy. J Allergy Clin Immunol 1990;85:1030-9. (grade B)
70. Mabry RL Allergic and infective rhinosinusitis: differential
diagnosis and interrelationship. Otolaryngol Head Neck Surg
t994;111:335-9. (grade C)
71. Klossek JM, Dubreuit L, Richer H, et al. Bacteriology of the
adult middle meatus. J Laryngol Otol 1996;110: 847-9. (grade B)
72. Polmar SH. Approach to the child with immune deficiency. Curr
Views Allergy Inmrunol 1994;22:1-11.
73. Polmar SH, Kemp ME. lmmunodeficiency diseases. !n:
Korenblot PE, Wedner HJ, editors. Allergy: theory and practice.
Philadelphia: WB Sannders Co, 1992:103-28.
74. Sethi DS, Winkelstein JA, Lederman H, et al. Immunologic
defects in patients with chronic recurrent sinusitis: diagnosis and
management. Otolaryngol Head Neck Snrg 1995;112:242-7.
(grade B)
75. Scadding GK, Lund VJ, Darby YC, et al. IgG subclass levels in
chronic rbinosinusitis. Rhinology 1994;32:15-9. (grade B)
76. Ambrosino DM, Siber GR, Chilmonczyk BA, et al. An immun-
odeficiency characterized by impaired antibody responses to
polysaccharides. N Engl J Med 1987;316:790-3. (grade C)
77. Wasserman RL. Immunodeficiencies. Curt Opin Otola'yngol
Head Neck Surg 1994:2:99-103. (grade C)
78. Sethi CS, Leopold DA. Diagnosis and management of chronic
recurrent sinusitis and immunoglobulin deficiency. Curt Opin
Otolaryngol Head Neck Surg 1995;3:21-255. (grade C)
79. McCaffrey TV, McDonald TJ. Sarcoidosis of the nose and
paranasal sinuses. Laryngoscope 1983;93:1281-4. (grade C)
80. Shikowitz MJ, Alvi A. Sarcoidosis presenting as nasal obstmc~-
tion. Am J Rhinol 1993;7:133-8. (grade C)
81. gaespi YR Kuriloff DB, Aner M. Sarcoidosis of the sinonasai
tract: a new staging system. Otolaryngolol Head Neck Surg
i995;112:221-7.
82. Lazarus AA. Sarcoidosis. Otolaryngol Clin North Am
1982;15:621-33. (grade C)
83. James DG, Barker S, Jash D, et al. Sarcoidosis of the upper res-
piratory tract. J Laryngol Otol 1982;96:711-8.
84. Lieberman J. Elevation of serum angiotensin-convertingenzyme
(ACE) level in sarcoidosis. Am J Med 1975;59:365-72. (grade
C)
85. Wilson R, Lurid V, Sweatman IS, et al. Upper respiratory tract
involvement in sm'coidosis and its management. Eur Respir J
1988;1:269-72. (grade C)
86. Devaney KO, Travis WD, Hoffman G, et al. Interpretation of
head and neck biopsies in Wegener's granulomatosis: a patho-
logic study of 126 biopsies in 70 patients. Am J Surg Pathol
1990;14:555-64. (grade B)
87. Fauci AS, Wolff SM. Wegener's granalomatosis. Medicine
1973;52:535-6t. (grade B)
88. Vartialnen E, Nuutinen J. Head and neck manifestations of
Wegener's granulomatosis. Ear Nose Throat J 1992;71:423-8.
(grade C)
89. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulo-
matosis: an analysis of 158 patients. Ann Intern Med
/992;116:488-98. (grade B)
90. Van der Woude FJ, Lobatto S, Pertain H, et aI. Autoantibodies
against neutrophils and monocytes: tool for diagnosis and mark-
er of disease activity in Wegener's granulomatosis. Lancet
t985;1:425-9. (grade B)
91. Nolle B, Specks U, Ludemann J, et al. Anticytoplasmic autoan-
tibodies: their immunodiagnostic value in Wegener's granulo-
matosis. Ann Intern Med i989; 11:28-40. (grade A)
92. Sneller MC. Wegener's granulomatosis. JAMA 1995;273:I288-
91. (grade C)
93. Andrews JT, Kountakis SE. Wegener's granulomatosis of the
skull base. Am J Otolaryngol 1996;17:349-52. (grade C)
94. Rosenstein BJ. Making and confhming the diagnosis. In:
Orenstein D, Stern RC, editors. Cystic fibrosis. Philadelphia:
Lippincott Raven, 1997. In press. (grade C)
95. Stern RC, Boat TF, Wood RE, et al. Treatment and prognosis of
nasal polyps in cystic fibrosis. Am J Dis Child 1982;136:1067-
70. (grade C)
96. Shwachman H, Kulczycki LL, Mueller HL, et al. Nasal polypo-
sis in patients with cystic fibrosis. Pediatrics 1962;30:389-401.
(grade C)
97. Wiatrak BJ, Myer CM, Cotton RT. Cystic fibrosis presenting
with sinus disease in children. Am J Dis Child 1993;147:258-60.
(grade C)
98. Kulczycki LL, Murphy TM, Bellanti JA. Pseudomonas colo-
nization in cystic fibrosis. JAMA 1978;240:30-4. (grade C)

15. $26 FERGUSONand MABRY
Otolaryngology-
Head and Neck Surgery
September 1997
99. Fitzpatrick SB, Rosenstein BJ, Langbaum TS. Diagnosis of cys-
tic fibrosis during adolescence. J Adolesc Health Care
1987;7:38-43.
100. Gibson LE, Cooke RE. A test for concentration of electrolytes in
sweat in cystic fibrosis of the pancreas utilizing pilocarpine by
iontophoresis. Pediatrics 1959;23:545-9. (grade A)
101. Webster HL, Barlow WK. New approach to cystic fibrosis diag-
nosis by use of an improved sweat induction/collection systems
and osmometry. Clin Chem 1981;27:385-7. (grade A)
102. Kingdom TT, Lee KC, Cropp GJ. Chronic sinusitis and a nega-
tive sweat test in a patient with cystic fibrosis. Am J Rhinol
1995;9:225-8. (grade C)
103. Gowen CW, Lawson EE, Gingras-LeathermanJ, et al. Increased
nasal potential difference and ameliorate sensitivity in neonates
with cystic fibrosis. J Pediatr 1986;108:517-21. (grade B)
104. Alton EWFW, Currie D, Logan-Sinclair R, et al. Nasal potential
difference: a clinical diagnostic test for cystic fibrosis. Eur
Respir J 1990;3:922-6. (grade B)
105.Alton EWFW, Hay JG, Munro C, et al. Measurement of nasal
potential difference in adult cystic fibrosis, Young's syndrome,
and bronchiectasia. Thorax 1987;42:815-7. (grade A)
106. Kerem B, Rommens JM, Buchanan JA, et al. Identification of
cystic fibrosis gene: genetic analysis. Science 1989;245:1073-
80. (grade A)
107. Kingdom TT, Lee KC, FitzSimmons SC, et al. Clinical charac-
teristics and genotype analysis of patients with cystic fibrosis
and nasal polyposis requiring surgery. Arch Otolaryngol Head
Neck Surg 1996;122:1209-13. (grade B)
108.Ballenger WL, Ballenger HC. The etiology, pathology, symp-
toms and diagnosis of sinus infections. In: Ballenger WL,
Ballenger HC, editors. Diseases of the nose, throat and ear.
Philadelphia: Lea & Febiger; 1943. p. 148-57. (grade C)
109.Mabry RL. Officediagnosis of sinus disorders: the role of ultra-
sound scanning. Laryngoscope 1984;94:1042-4. (grade C)
ll0. Williams JW Jr, Simel DL. Does this patient have sinusitis?
Diagnosing acute sinusitis by history and physical examination.
JAMA 1993;270:1242-6. (grade A)
111.Pfister R, Lutolf M, Schwapowal A, et al. Screening for sinus
disease in patients with asthma: a computed tomography-con-
trolled comparison of A-mode ultrasonography and standard
radiography. J Allergy Clin Immunol 1994;94:804-9. (grade B)
112. Rohr AS, Spector SL, Siegel SC, et al. Correlation between A-
mode ultrasound and radiography in the diagnosis of maxillary
sinusitis. J Allergy Clin hnmunol 1986;78:58-61. (grade C)