Evaluating rhinitis: Clinical, rhinomanometric, and cytologic assessments

BlJSSf?

J CLiERG’I

be possible to correlate changes in nasal physiology with measurements of the allergic reaction. Correlation of these parameters with therapeutic approaches promises a more precise understanding of nasal disease and new directions in treatment. REFERENCES I. Do&horn RJ, Shellenberger MK. Antihistamines: the new generation. Immunol Allergy Pratt 1987;9:124-33. 2. Spector SL. The pharmacology of antihistamines. J Respir Dis (monogr series) 1987;7:24. 3. Norman PS. Allergic rhinitis. J ALLERGY CLIN IMMUNOL 1985;75:531-50. 4. Mygind N. Pharmacotherapy of nasal disease. NER Allergy Proc

1985;6:245-8.

5. Handelman NI, Friday GA, Schwartz HJ, et al. Cromolyn sodium nasal solution in the prophylactic treatment of polleninduced seasonal allergic rhinitis. J ALLERGY CLIN IMMUNOL

.:ilN IMMliNOt. “4VEMBEFf 1988

6. Siegel SC. Coiticosteroids in the treatment ot nasal allergy. In: Siegel SC, ed. Current concepts in allergi< rhmitis. I .4 comparison of agents. Monograph, 1986: 14-Z:’ 7. Norman PS, Review of nasal therapy: update. 1 AI.I F.IK~~ CI.IN IMMUNOL1983;72:421-32. 8. Clayton DE, Kcloistra JB, Geller M, et al. Short-term elticacy trial and 24-month follow-up of flunisolide nasai spray in the treatment of perennial rhinitis. J ALLERGY ('t.ih I.MMIIW 1981;67:2-7. 9. Dickson DJ, Cruickshank JM. Clinical trial of tlunisolide and terfenadine in the symptomatic treatment of hay fever. In: Siegel SC, ed. Cummt concepts in allergic rhinitin. 11 Flunisolide: theory and practice. Monograph 1986:9-14. 10. Welsh PW, Snicker WE. Chu C-P, et al. Efficacy of bcclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy. Mayo Clrrl Proc 19x7: 62~125-34. 11. Graft DF, Valentine MD. Immunotherapy. In: Kaplan AI’, cd. Allergy. New York: Churchill Livingstone. I9RS.67992

1977;59:237-42.

ng rhinitis: Clinical, Eva and qtologic assessments Eli 0. Meter,

rttho

MD Sun Diego, C&f.

Allergic rhinitis is a common disease.Its diagnostic accuracy can be improved by quanttjkble methods, such as scoring symptoms and signs, rhinomanometry, and the examination of nasal cytologic specimens.These methods are fast* easy to use, and well tolerated by patients. The same methods can also be used to follow changes as they occur with treatment. For example. improvements can be documented in patients with allergic rhinitis receiving topical corticosteroids, including jfunisolide. Flunisolide therapy decreasesthe symptoms, improves the patency of the nasal airways, and leads to more normal nasal cytologic studies in patients with allergic rhinitis. (J ALLERGY CLIN LUMUNOL 1988;82:900-8.)

Rhinitis, a general term for disorders of the nasal mucosa, chronically affects about 40 million Americans (Fig. 1). The exact figure for prevalence is not available, but based on health interview surveys it is estimated to be as high as 18%.’ Although chronic rhinitis is sometimes thought to be a trivial illness, the morbidity and economic burdens associated with it are immense. A 1975 survey’ concluded that as the result of allergic rhinitis in 1 year alone, Americans were restricted in their activities 28 million days, were bedridden 6 million days, and lost 2 million school days. Furthermore, this illness cost Americans

From the Allergy and Asthma Medical Group and Research Center, University of California School of Medicine, San Diego, Calif. 900

500 million dollars for physician services and medications.

Patients with chronic nasal symptoms need to be evaluated systematically. An effective therapeutic approach is more likely to be developed if the diagnosis is accurate, and the diagnosis is more likely to be accurate if it is based on a careful history and, physical examination, supplemented with the appropriate laboratory studies. The major points of the history are listed in Table I. When was the onset of symptoms: infancy, chitdhood, or ad&hood? Did the symptoms OCCQF after an upper respiratory tract infection, after trauma. or after moving to a new h’ome or acquiring a new pet? How

Evaluating

VOLUME 82 NUMBER 5, PART 2

rhinitis

901

Millions so 58.7 million 25.0% of the total population 41.5 milfh 11.7% of tflo total popul8tkm 24.8 nlllfion 10.6% of the total popuwon

U.k.A.

FIG. 1. Incidence

of type of allergy.

U.R.A.,

upper respiratory

allergy.

TABLE I. When rhinitis is suspected: Major points in a history Onset of symptoms

Infancy, cbildbood, adultllood After upper respiratory tract infection After trauma After moving or acquiring a new pet Frequency of symptoms Daily Seasonal Episodic Unremitting Duration of symptoms Weeks Months Y&U8 Severity of symptoms Mild Annoying Distressing

frequent are the symptoms? Are they daily, seasonal, episodic, or unremitting? How long has the patient had the symptoms? How severe are they? Are they mild, annoying, or distressing? Do they interfere with sleep or disturb the patient emotionally? What are the symptoms? What are the character and color of the secretions? Are there precipitating factors, such as allergens, irritants, or climatic conditions? Are there associated factors, such as systemic or local disorders, infections, or medications? These points in a patient’s history can aid in understanding the pathogenesis of

Types of symptoms Sneezing Itching Obstruction Runny noseI sniffing coughing Postnasal drip Character and color of secretions Watery, clear Mucoid, opaqque Purulent, discolored Precipitating factors Allergens Irritants Climatic conditions Associatedfactors Systemicor local disorders Infections Medications

the nasal symptoms and thereby help determine the most effective treatment program. Tbe second aspect of assessing a patient’s nasal disorder is the physical examination. As seen in Table II, the physical examination for individuals with complaints of chronic rhinitis must include, in addition to the nose, the eyes, the ears, the sinuses, the mouth, the phstynx, and the chest. The eyes are examined with a pen light. This will reveal serious cases of phomphobia and demonstrate possible corneal involvement. Conjunctival signs include injection, lac-

902 Meltzer TABLE II. When rhinitis is suspected: Major points in a physical examination Eyes Photophobia Injected conjunctiva Increasedlacrimation Mucus discharge Blepharitis Puffy or baggy lids increasedfurrows of the lower lids (Dennie lines) Cyanosis of infraorbital area (shiners) Ears Eustachiantube dysfunction infection Fluid Sinuses Tender when palpated Mouth and pharynx Lip or gingival inflammation Orthodontic abnormalities Quality and quantity of secretions Abnormal growths Chest Adventitious sounds on auscultation, suggesting asthma or bronchitis Nose External shape Nasal crease Nostril inflammation Position of septum Appearanceof turbinates Quality and quantity of secretions Abnormal obstructions

rimation, and discharge. The upper lids are examined for blepharitis and puffiness, whereas the signs of rhinitis on the lower lids include bags, increased furrows (Dennie lines), and “shiners.” Examination of the ears includes evaluation of eustachian tube function by pneumatic otoscopy or impedance tympanometry. The ears are also examined for infection and fluid. The sinuses are palpated for tenderness. The lips and gingivae are assessed for inflammation, the teeth for orthodontic abnormalities, and the pharynx for secretions, erythema, or abnormal growths. The chest is examined for adventitious sounds on auscultation suggestive of asthma or bronchitis. The external shape of the nose is examined. The nose is examined for a nasal crease or nostril inflammation. Position of the septum, appearance of the turbinates, and quality and quantity of secretions are noted, as is the presence of abnormal obstructions.

J ALLERGY CLIN. IMMUNOL. NOVEM~R 1988

TABLE IN. Scores for rhinitis symptoms Score

Symptom

Sneezing/itching 0 Absent 1 Mild; I to 4 sneezesper day or occasional itching 2 Modemte; 5 to 10 sneezesper day or annoying itching continuous for -230 min 3 Severe:,distressing spells or fits that may interfere with sleep or concentration Nasal congestion 0 Absent 1 Mild; some hindrance to breathing. not uncomfortable 2 Moderate; nostril(s) feel blocked, need to breathe through mouth most of time; annoying 3 Severe;cannot breathe comfortably through nose at all; may interfere with sleep, alter odor perception, or affect quality of voice Runny nose/ sniffing 0 Absent 1 Mild; sniffing or tissuesneeded 1 to 4 times daily 2 Moderate; sniffing or tissuesneeded 5 to IO times daily 3 Severe; nose runs freely despite frequent use of halndkerchiefor tissues Postnasaldrip/ snorting 0 Absent I Mild; slight awarenessor tickling sensation in throat 2 Moderate; causesfrequent throat clearing; annoying 3 Severe; causesgagging or frequent cough; uncomfortable

After the identification of a patient’s symptoms and signs, they can be quantified by a scoring system. The scores provide a measure of the severity of the patient’s rhinitis. Table III provides the scoring system

for the symptoms of sneezing or itching, nasal congestion, runny nose or sniffing, and postnasal drip or snorting. Table IV provides a Qpoint scale for the rhinitis signs of turbinate mucosal color, turbinate swelling, nasal discharge, and pharyngeal inflammation. Certainly, the more frequent or severe the

patient’s “disease,” as measured by the scoring system, the clearer is the necessity for therapeutic interventions.

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VOLUME 82 NUMBER 5, PART 2

/

-

Tube measures retronasal pressure P, Al

FIG. 2. Patient

TABLE

undergoing

IV. Scores

anterior

for rhinitis

Score

rhinomanometry.

903

Pneumotachometer

m

At&spheric pressure to transducers

FIG. 3. Diagram of anterior rhinomanometry technique. Flow rate is that measured at a defined differential pressure (p, - p2) of - 1.5 cm H,O. (Adapted with permission from Welch MJ, Meltzer EO, Orgel HA, Kemp JP. Ann Allergy 1985;55:577-9. Copyright 1985 American College of Allergy and Immunology.)

signs Sign

Turbinate mucosal color 0 Normal; lip color pink Mild; slightly reddened or paler pink lips 1 2 Moderate; reddened or pale lips 3 Severe; inflamed, anemic, or blue lips Turbinate swelling 0 Absent Mild; enlargement or prominence of either in1 ferior or middle turbinate with slight blocking of nasal airway Moderate; turbinate congested, compromising 2 one or both nasal airways Severe; turbinates occlude one or both nasal 3 airways Nasal discharge 0 Absent Mild; mucous membranes appear moist 1 throughout Moderate; secretionsvisible on turbinate or on 2 floor of nasal passage Severe; profuse, filling passageor draining 3 Pharyngeal inflammation Absent 0 1 Mild; posterior oropharynx slightly reddened 2 Moderate; posterior oropharynx reddened or follicular in appearance 3 Severe; mucus clearly visible on posterior oropharyngeal wall

RHlNOMANOMETRY OF RHINlTlS

rhinitis

IN THE DIAGNOSIS

Rhinomanometry is a third method for the evaluation of rhinitis. It is a technique for objectively quan-

FIG. 4. The Rhinoprobe.

tifying the symptoms of nasal obstruction and the signs of mucosal swelling that physicians traditionally follow subjectively for rhinitis.3 As seen in Fig. 2, measurement of nasal air flow can he performed simply, rapidly (in less than 30 seconds), and easily (even with the pediatric patient). Fig. 3 is a diagram of the anterior rhinomanometry technique. It is so called because all measurements are obtained from the exterior surface of the nose. A pneumotachometer calibrated for flow rate is fitted with a plastic, rubber-tipped nosepiece and placed against the opening of one nostril. As the patient inspires, air moves through the pneumotachometer. A pressure gauge on the pneumotachometer measures external nares pressure. Another similar nosepiece is placed against the other nostril and is connected to a pressure transducer, which records the pressure within the nostril (reflecting the retronasal pressure). The flow rate is measured

904

Meltzer

j. ALIERGY

FIG.

5. Sampling

TABLE V. Aaaociation of air flow measured chiMren with perennial allergic rhinitis Vn Air flow

p < 0.01

of epithelial

nasal

mucosa

by rhinomanometry

Totat symptom

p c 0.05

score

CLIN. IMMUNOL. NCVEMBEP 7988

by with

other

patient

variables*

in 49

Mucos8lswalf9ng p < 0.01

p <: 0.01

A

with ~E&&+wI from Welch MJ, Meltzer EO, Orgel HA, Kemp JP. Ann Allergy 1985; 55577-9. Copyright 19M American ofAlkgya3dl3Mmaotcgy. *AM&& dose witIt Pearson product-moment correlation coefficient (& = 48).

ure between the external space of - 1.5 cm H,O and an XY recorder, or a direct t. When a satisfactory recording has been obtaked, the tubes are switched to measure the other nasal airway. Anterior rhinomsnornetry has the additional advantage of providing information about the patency of es& nasal airway. The readings from the two nostrils canbesummedtoobtainameasureofthetotalnasal air flow. Table V lists results of a study of 49 children with a diagnosis of perennial allergic rhinitis, based on clinical featues, skin tests, and nasal cytologic findings. The total symptom score (especially the subjective symptom of congestion) and the total physical sign W (specilklly, the score of mucous membrane swelling) both correlated well with nasal air flow as measmed by anterior rhinomanometry.3 IuMALerrocoGY Analysis of nasal cytologic findiugs can be a critical tool in the evaluation of rhinitis. As shown in Table VI, nasal cytologic studies can aid in classifying the vi&al patients into inflammatory, nonand structurally induced categories. It also differentiates between allergic, nonallergic, and

infectious forms of rhinitia and between bacterial and viral infection.4 The use of a disposable plastic Rhinoprobe scoop (Synbiotics Corp., San Diego, Calif. ; Fig. 4) to obtain a specimen is bet&r than &kg on expelled mucus. Table VII outlines the steps in mucosal sampling with the EZhinoprobe. Fig. 5 is a diagmmmatic view of sampling with the Rhkoprobe in sagittal and cross-sections. Fig. 6 is a facial view during Rhinoprobe sampling. Table VIII outlines the method of applying the specimen to a slide, and Table IX presents the method for staining the ceils in the nasal mucus. Analysis of the nasal cell specimen can classify responses as normal (epithelial cells mairdy; Fig. 7) or eosinophilic (Fig. 8), basophilic (Fig. 9), neutrophilic (Fig. lo), or goblet cell types (Fig. 11). lncrease in nonepithelial cells are associated with various diagnostic possibilities, as shown in Table X. Increased eosinophik can be atmkatd with allergic rhinitis, nonallergic e43sinophilic rhirritis, or aspirin sensitivity. Increased baqhils can be dated with ik d&&is, asakrgic Ihinitis, lnonauergic mapirin sensitivity, uonallergic rhinitis with ~~Iia, I.ncmwd n~trophils or primary nasal mastoc*is. with intrac&hdar bacteria are associated with Npsopharyngitis or sinusitis. Increased neutrophils with no

Evaluating

VOLUME 82 NUMBER 5. PART 2

FIG. 7. Normal

FIG. 6. Rhinoprobe sampling. (Jalowayski AA, Gershwin ME, Nagy SM Jr. Clinical allergy series. Part XIV: Nasal cytology. By Medcom Inc., reproduced by permission of Medcom Inc., Garden Grove, Calif.)

TABLE

VI. Classification

of chronic

nasal

rhinitis

905

cells.

rhinitis

Inflammatory rhinitis Eosinophilic allergic rhinitis Seasonal Perennial Eosinophilic nonallergic rhinitis Infectious rhinitis Viral Bacterial Nasal polyposis Nasal mastocytosis Atrophic rhinitis Noninflammatory rhinitis Vasomotor rhinitis Autonomic dysfunction Associatedwith systemic conditions Pregnancy Thyroid disease Rhinitis medicamentosa Local sympathomimetic overuse Systemic medications Antihypertensives Contraceptives Structure-related rhinitis Anatomic deformities Septal deviations Ciliary disorders Obstructions Adenoidal hypertrophy Foreign bodies Tumors

FIG. 8. Eosinophils.

can he associated with viral upper respiratory tract infection. Increased neutrophils with ciliocyto-

bacteria

phoria may also be associated with viral upper respiratory tract infection. Increased goblet cells can be associated with allergic rhinitis, infections, or, possibly, vasomotor rhinitis . Combining the information obtained from the history, physical examination, rhinomanometry, and na-

906

Meltzer

? ALLERGY CLN. IMM1INOL W’/EMBEH 1958

FIG.

FIG.

9. Basophils.

11. Goblet

TABLE VII. Mucosal the Rhinoprobe 1. 2. 3. 4. 5.

sampling

cells.

with

Under direct vision, gently maneuver cupped tip to mid portion of inferior turbinate. Avoid contact with septum and anterior surfaces Gently press tip of probe on mucosal surf&c of inferior turbinate. Quickly move probe outwardly 2 to 3 mm Repeat once or twice if insufficient \ampk: i\ obtained.

TABLE WI. Application

of specimen

to slide

1. Spread contents of cupped tip of Rhinoprobe over slide. 2. Immediately place slide in jar containing CrS’% ethyl alcohol. 3. Fix for 30 to 60 seconds. 4. Stain either immediately or later. _.----FIG.

10. Neutrophils.

sal cytology, along with skin tests and other laboratory tests, we can differentiate various rhinopathies more precisely. ’

TOPICAL C43KllCOSTEl?OlD FOR ALLERGIC FIHMITIS

TREATMENT

The most common rhinopathy, diagnosed by history, physical examination, rhinomanometry, and na-

sal cytology, is allergic rhinitis. Once diagnosed, allergic rhinitis can be effectively treated with topical corticosteroids. Indeed, the efficacy of this form of treatment can be documented by the changes in the parameters we have just reviewed. In one study’ of 44 patients with allergic rhinitis, nasal symptoms were scored as shown in Table III and were followed for 15 days. Fig. 12 shows that with topical corticosteroid treatment, the decline in symptoms was significant at

Evaluating rhinitis 907

VOLUME 82 NUMBER 5. PART 2

Mean flaw oo/sec(rt: SE)

Totsl mean symptom scorn (5 SE)

, 6500

5400

43-

300

29

200

l-

166

k+

l .

l

1 1

4

6 Tmatment

16 day

Fffi. 12. Mean nasal symptom scores combined for 44 patients with allergic rhinitis receiving topical corticosteroids. l *p < 0.01, ***p < 0.01 compared with baseline. (Adapted with permission from Orgel HA, Meltzer EO, Kemp JP, Welch MJ. J ALLERGY CLIN IMMUNOL 1986;77:85864.)

TABLE IX. Dip method

of staining

1. Remove slide from ethyl alcohol. 2. Blot edge of slide to remove excessalcohol. 3. Dip slide in Wright-Giemsa stain for 10 to 15 seconds. 4. Drain excessstain. 5. Dip slide in Volu-Sol* buffer for 15 to 30 seconds. 6. Drain excessbuffer. 7. Dip slide in Volu-Sol* hematology rinse for 4 to 5 seconds, using quick dips. 8. Blot edge of slide and wipe back. 9. Use air blower to expedite drying. *L,ogosScientific,Inc., Henderson,N.Y.

days 4, 8, and 15. Mean nasal airflow, as measured by rhinomanometry (Fig. 13), also improved significantly during the 2-week treatment period. Table XI shows that eosinophils, measured by scores from 0 (no cells) to 4 (clumps of cells covering all the field), declined significantly with treatment. Although the declines in basophils, goblet cells, and neutrophils were not statistically significant, they, too, showed a downward trend with topical corticosteroid therapy. CONCLUSION The diagnostic evaluation of nasal disorders, including the most common form, allergic rhinitis, can be improved by more objective and quantifiable methods, such as the scoring of symptoms and signs and the use of rhinomanometry and nasal cytology. Each of these methods is quick and easy to use and well

O;

Treatment

day

FIG. 13. Mean nasal airflow for patients with allergic nitis receiving topical cotticosteroids (n = 43). *p c **p < 0.001 compared with baseline. (Adapted with mission from Orgel HA, Meltzer EO, Kemp JP, Wekh J ALLERGY CLIN IMMUNOL 1986;77:858-64.)

TABLE X. Nasal cytology: cytogram slide

rhi0.02, perMJ.

Interpreting

Increasedeosinochils Allergic rhinitis Nonallergic eosinophilic rhinitis Aspirin sensitivity Increased basophils Allergic rhinitis Nonallergic cosinophilic rhinitis Aspirin sensitivity Nonallergic rhinitis with basophilialprimary nasal mastocytosis Increased neutrophils With intracellular bacteria: Nasopharyngitis or sinusitis With ciliocytophoria: Viral upper respiratory tract infection With no bacteria: Viral upper respiratory tract infection Increased goblet cells Allergic rhinitis Infection Vasomotor rhinitis (?)

tolerated by patients. Furthermore, in addition to offering the advantage of developing a more accurate diagnosis, they can be used collectively to help document changes with treatment. With the use of these assessments, we have objectively confirmed the improvement of many patients with allergic rhinitis who have been treated with topical corticosteroids, including flunisolide. With flu-

808

J Ai LERGY CtiN. IMMUNOL. WVEMBER 13f38

Meltzer

TABLE Xl. Mean nasal cytology scores before and after 15 days of topical steroid treatment for allergic rhinitis

Day

Eosinophils Basophils

1

1.53* 0.96

Goblet cells

1.55

Neutrophils

0.30

Day

15

0.64* 0.57 1.16 0.16

Adapted with permission from Orgel HA, Meltzer EO, Kemp JP, Welch MJ. J ALLERGY CLIN IMMUNOL 1986;77:858-64. *p < 0.001 compared with baseline.

nisolide therapy, symptoms have decreased, nasal airways have become more patent, and nasal cytologic findings have become more normal. We recommend these methods in the evaluation and management of patients with nasal disease.

Meltzer EO, Zeiger RS, Schatz M, Jalowayski A. Chronic rhinitis in infants and chiidren: etiologic, diagnostic, and therapeutic considerations. Pediitr Clm North Am 1983;30:847-71. Young P. Asthma and Allergies: an optimistic future. U.S. Department of Health and Human Services; U.S. Public Health Service, National Institutes of Health (DIHN. 80-388, March 1980.) Welch MJ, Meltrar EO, Orgel HA, Kemp JP. Assessment of the carrelations of rhinomanomehy with the symptoms and signs of allergic rhiiitis in children. Ann Allergy 1985;55:577-9. 4. Meltzer EO. The current outlook on chronic allergic rhinitis. J Respir Dis 1985;6:100-23. 5. Orgel HA, Meltzer EO, Kemp JP, Welch MJ. Clinical, rhinomanmetric, and cytdogic evahmti011of seasonal allergic rhinitis treated with becIomet&ou e dipropionate as aqueous nasal spray or pressurized aerosol. J ALLERGY CLIN IMMJNOL 1986;77:858-64.

DBWSSlON Dr. Shapiro: Are rhinomanometry and nasal cytology easily available to the patient in the general office, or are these techniques offered only in an academic setting? Dr. Meltzer: Although rhinomanometry is becom-

ing available at many centers, nasal cytology is already available to everyone. Primary care physicians are starting to use nasal cytology more to provide critical additional information for the diagnostic evaluation. Dr. Busse: What mistakes do primary care physicians make in either misdiagnosing or underdiagnosing nasal disease? Dr. Meltzer: Physicians who see many patients with different problems sometimes find it difficult to sense that, for the patient, nasal disease call be as concerning as hypertension, diabetes, or malignancy. The issue is not whether nasal disease is or is not as concerning-but that it is concerning to the patient. The primary care physician needs to note how long the patient has had the symptoms and how frequent and severe they are. Often, the patient’s complaints must be understood as persisting over weeks, months, and even years. Neither the patient’s condition today nor the severity of his or her condition compared with that of other patients is basis enough for understanding. The patient’s concern must be our concern. Fortunately, for the patient who finds an understanding physician, the therapy of respiratory diseases has become very effective over the past 30 years. Unfortunately, the: knowledge of these effective therapies is not well spread among primary care physicians, and many of them are still using the older, less effective medications that often have troubling adverse effects. Patients are not willing to trade off their symptoms for these adverse effects. One of the benefits of a symposium such as this is sharing with the primary care physician the message that wonderful new therapies are available, and that patients do not need to be uncomfortable anymore. Dr. Naclerio: Are you finding that other physicians are using your scoring system for rhinitis signs and symptoms? If so, are they using it to follow the therapeutic effectiveness of various agents, such as flunisolide? Dr. Me&m: Yes, we are finding that a scoring system is being adopted by many physicians. They do indeed find it helpful to have a more objective reflection of improvement, for example, of nasal congestion with llunisolide treatment. rather than having only the patient’s general subjective assessment.