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Allergic airway disease and otitis media in children
InternationalJournalofPediatNcOtorhinolao,ngologv, 10 (1985) 27-35
27
Elsevier
P O R 00327
Allergic airway disease and otitis media in children N. W e n d e l l T o d d a n d Clyde M. F e l d m a n Department of Otorhinolar~'ngology and Communication Sciences. Phoenix Indian Medical Center, 421'2 N. 16th Street. Phoenix, A Z 85016, and Department of Family and Community Medicine. Universit); of A rizona Medical Center. Tucson, A Z 85724 (U.S.A.) (Received October 15th, 1984) (Revised May 14th, 1985) (Accepted June 8th, 1985)
Key words: allergic rhinitis - asthma - eustachian tube - otitis media
Summary The occurrence of allergic rhinitis, asthma and otitis media was examined in 395 Indian children living on two separate reservations in Arizona. The children were followed from birth to age 5 years in a study of otitis media. On retrospective review of medical records, 45% of the children at Parker had a clinical diagnosis of allergic airway disease, in contrast to only 6% at San Carlos. At each site, about 55% had recurring otitis media in infancy; of these otitis-prone infants, 40% at Parker and 36% at San Carlos persisted to have 3 or more episodes of otitis media after age 2 years. The only allergic airway disease correlate with otitis media was allergic rhinitis in children age 2-4 years.
Introduction
The relation of allergic airway disease to otitis media is controversial, with some [19,16] endorsing a very strong (90%) cause-effect relationship, and others [4,6,18] suggesting a much smaller relationship. With some exceptions [11], studies endorsing a relationship are not randomized or controlled, and do not consider treatment modalities other than allergic [2]. We present an epidemiologic study involving patients selected for having neither allergic airway disease not otitis media. Correspondence: N.W. Todd. Present address: Emory University School of Medicine. 1365 Clifton Road. Atlanta, G A 30322, U.S.A.
0165-5876/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
28
Background of the study A prospective study from birth of native American Indian children living on 4 separate reservations in Arizona began in 1974 to identify environmental correlates of the high occurrence of otitis media. No environmental correlate of otitis media in infancy was found [21]. The natural history of otitis media has been documented in these children: an infant with two or more clinical encounters for separate occurrences of otitis media is 'high risk' for having subsequent episodes of otitis media in the first two years of life [8]. Most of the initial attacks of acute suppurative otitis media occur during the first year of life, and most subsequent attacks occur within 4 months of a prior attack. A child aged 2 - 4 years, with 3 or more clinical encounters for separate occurrences of otitis media, is considered to have 'persistent' otitis media problems. These categories are epidemiologically sound whether the specific clinical diagnosis at a particular time is acute suppurative otitis media, chronic otitis media (tympanic membrane perforation for more than 3 weeks), or middle ear effusion. The winter seasonal exacerbation of otitis media problems is the same for each of the diagnostic categories, and for patients living at each of the 4 reservations. Zero or only one clinical encounter for otitis media in the initial two years of life associates with a 9570 likelihood of a child not having 'persistent' otitis [20].
Materials and Methods Review of the cohorts at the Colorado River Indian Reservation, at Parker in western Arizona identified 160 patients as having had essentially continuous medical care at the local United States Public Health Service Indian Hospital for the first 5 years of life. Each patient's medical record was reviewed for the date of encounter for any of the following physician-made diagnoses: 'allergic rhinitis', 'hay fever', 'reactive airway disease', and 'asthma'. Additionally, each record was searched regarding eosinophilia (not attributable to parasitic infection) on peripheral blood smear, serum IgE, nasal smear for eosinophils, skin test documentation of allergic airway disease, and allergist's diagnostic assessment. The data of children at another otitis media project site were similarly studied: San Carlos, an Apache reservation in eastern Arizona. Two hundred and thirty-five children were identified as having had presumably continuous medical attention at the U.S.P.H.S. Indian Hospital there. Standard diagnostic criteria for otitis media were used [8,21]. Generally accepted diagnostic criteria for allergic airway conditions are assumed. Some uniformity of allergic airway diagnoses may have been afforded by the involvement at these study sites of just one otolaryngologist [NWT]. In addition to providing telephone consultation to physicians on these reservations and seeing the patients in Phoenix for consultation and surgery, he made approximately monthly visits to each reservation's hospital from July 1974 to June 1984. These 'field clinics' provided an opportunity for patients to be seen in consultation, for the primary care physicians to confer with the otolaryngologist, and for the otolaryngologist to monitor the quality of care (including documentation in the patient medical records).
29 F o r the p u r p o s e s of this study, hay fever a n d allergic rhinitis d i a g n o s e s were g r o u p e d a n d c o n s i d e r e d ' a l l e r g i c rhinitis'. Similarly, a s t h m a a n d reactive a i r w a y d i s e a s e were g r o u p e d a n d c o n s i d e r e d ' a s t h m a ' . Statistical a s s e s s m e n t was p e r f o r m e d with the x2-test.
Results T h e p a t t e r n s of o c c u r r e n c e of otitis m e d i a were strikingly similar at the two r e s e r v a t i o n s ( T a b l e I). Before two years of age, a b o u t 55% of the c h i l d r e n had at least two s e p a r a t e clinical e p i s o d e s of otitis media. A t Parker, 40% of these o t i t i s - p r o n e i n f a n t s p e r s i s t e d to have 3 or m o r e e p i s o d e s in the next 3 years; at San C a r l o s , 36%. Likewise, the ' n o t high risk' followed b y ' p e r s i s t e n t ' otitis p a t t e r n was similar: 5.6% of the P a r k e r group, 5.1% of the San C a r l o s group. (These ' n o t high risk' then ' p e r s i s t e n t ' p a t i e n t s p r e s u m a b l y h a d silent otitis m e d i a d u r i n g the first two y e a r s o f life.) T h e r e c o r d i n g o f allergic a i r w a y disease o c c u r r e n c e was m a r k e d l y different (X 2 = 85, P < 0 . 0 0 1 ) at the two s t u d y sites: 45% at Parker, b u t o n l y 6% at San C a r l o s ( T a b l e II). A t Parker, 22 of the 160 c h i l d r e n were labelled as having a s t h m a ,
TABLE I PATTERNS OF OTITIS MEDIA AT PARKER AND SAN CARLOS * High risk, two or more clinical encounters for separate episodes of otitis media in the first two years of life; persistent, 3 or more clinical encounters for separate episodes of otitis media in a child age 2-4 years. Otitis media pattern
Parker
High risk. persistent High risk, not persistent Not high risk, but persistent Not high risk. not persistent Total
San Carlos
Total
35 53 9 63
46 80 12 97
81 133 21 160
160
235
335
* No significant difference.
TABLE I1 ALLERGIC AIRWAY DISEASE AT PARKER AND SAN CARLOS X2
= 85, P < 0.001.
Allergic airway disease Yes No Total
Parker
San Carlos
Total
73 87
14 221
87 308
160
235
395
30 T A B L E Ill A L L E R G I C A I R W A Y DISEASE VERSUS OTITIS M E D I A P A T T E R N IN C H I L D R E N LESS T H A N AGE 5 YEARS AT PARKER * Otitis media pattern
Allergic airway disease
High risk, persistent High risk, not persistent Not high risk, but persistent Not high risk, not persistent Total
Diagnosed
Not diagnosed
12 28 6 27
23 25 3 36
Total 35 53 9 63
'73
87
160
* No significant difference.
on 57 separate occasions. The median age for initial encounter for asthma was 28 months, with a range of 1-59 months. For allergic rhinitis, the total n u m b e r of encounters for the 69 children so diagnosed, at one time or another, was 204. The median age for initial encounter for allergic rhinitis was 12.5 months. Of the 22 children labelled as having asthma, 19 also had an allergic rhinitis diagnosis. Of the children considered clinically to have allergic airway disease, 26% (19/73) had additional information (4 had more than one positive supporting test) to support the diagnosis: 14 had eosinophilia > 5% on peripheral blood smear on at least one occasion; 3 had at least one elevated (for age) serum IgE, 2 had more than 20% eosinophils on at least one smear of nasal mucus, 2 had positive skin test responses to inhalent allergens, and 2 received an allergist's diagnosis without benefit of additional tests. Of the 14 San Carlos children diagnosed as having allergic airway disease, none had IgE, nasal or peripheral smear eosinophil data, nor skin testing to inhalant allergens, to support the diagnosis. Nine had asthma, the inverse of the allergic rhinitis to asthma ratio of diagnoses at Parker. If the diagnoses of allergic rhinitis were understated at San Carlos, and if the asthma diagnoses were valid, and if the true cumulative ratio of allergic rhinitis to asthma were 3 : 1 (the ratio found at T A B L E IV A L L E R G I C R H I N I T I S VERSUS OTITIS M E D I A P A T T E R N IN C H I L D R E N A G E 2 - 4 Y E A R S A T PARKER X 2 = 5.65, P < 0.02. Allergic rhinitis Diagnosed
Not diagnosed
Total
Persistent otitis Not persistent
22 33
22 83
44 116
Total
55
105
160
31 40-
t,-
35"
oo ¢ uJ
30.
u." "6_ 1-
asthma • allergic rhinitis • otitis media •
" t
,//
\I
20.
/ ',,,
15lo-
,/' ~ll \ I \;
O-
i~ ,' ""
'•-J ~ ' t
,,,' "" )k,,
/,i .... ,--.-at
Ii
A g e In M o n t h s
Fig. 1. Age distribution o f first encounters for allergic rhinitis, asthma, and otitis media among 150 Indian children at Parker.
Parker, and reported elsewhere [13,15]), then 32 children at San Carlos could be considered allergic. Even if all this were so, the allergic airway disease occurrence would still be markedly different (X 2 = 47, P < 0.001) than at Parker. An association of allergic airway disease with otitis media was difficult to identify (Table III). Multiple analyses of number of clinic visits for allergic airway diseases versus otitis media revealed only one association: children age 2 - 4 years, at Parker, with one or more clinical encounters for allergic rhinitis, were more likely (X 2 = 5.65, P < 0.02) to have 3 or more clinical encounters for otitis media (Table IV). The ages of first clinical encounter for asthma and allergic rhinitis are older than that for otitis media (Fig. 1). In contrast to the winter season increase of otitis media, neither allergic rhinitis nor asthma had a statistically significant seasonal trend. No birth month association with subsequent allergic airway disease or otitis media was discernible. Although the otitis media rates and patterns were similar in these two populations, the allergic airway disease rates were quite different. Only in children who had otitis media recurringly in infancy, did allergic rhini.tis subsequently correlate with otitis media. Children fortunate enough to have escaped two or more bouts of otitis media in infancy, did not have significant otitis problems in the next 3 years, even if allergic rhinitis became a health problem prompting repeated physician visits. Discussion
The present study suggests that the relationship between allergic airway disease and otitis media is weak. Our data are more likely to be accurate than parent recall
32 studies [7,11]. However, some qualifications limit the interpretation of our results. The diagnosis of allergic rhinitis is often difficult in infancy. A number of different physicians attended these children, and the criteria for allergic airway disease diagnosis were not standardized. Perhaps the involvement of the same otolaryngologist prompted some uniformity of diagnoses. Only 26% of the allergic airway patients at Parker, and none at San Carlos, had support for the diagnosis beyond the history and physical examination by the general physician. The variables of exposure to household pets, tobacco, and other inhalent allergens and irritants are unknown. Patient access to medical services, use of the services, and quality of the services at the two facilities are presumably equal. Lastly, the appropriateness of extrapolating these findings to other populations is unknown. The concordance of allergic rhinitis and asthma has been noted by others [3,13]. Our finding of a 3 : 1 ratio of cumulative occurrence, in the first 5 years of life, of allergic rhinitis to asthma at Parker is similar to that reported by others [13A5] in diverse geographies. As would be expected [1], for children exposed to essentially year-round inhalant allergens, neither birth month nor season correlated with allergic airway diagnoses. Why were allergic airway problems so common in our Parker group, in contrast to our San Carlos group and elsewhere [3,13]? The question is especially interesting because "allergic (extrinsic) asthma and other atopic diseases occur less often in native Americans than whites" [22]. We think the explanation of Johnstone [10], in addressing the occurrence of asthma in developed versus developing countries, is applicable: environmental rather than purely genetic factors explain the differences. The reservation at Parker, in contrast to San Carlos, is in an agriculturally highly developed irrigated valley. The Indian population at Parker is a mix of about 5% Chemehuevi, 40% Mohave, 20% Navajo, 20% Hopi, and 15% other tribes. In contrast, San Carlos Apaches are an essentially homogeneous genetic group. However, no attempt was made to assess the degree of Indian 'blood' for the individual patients of our study groups. The finding that clinical allergic airway disease epidemiologically did not correlate well with otitis media is not surprising. Some mucosal diseases (cystic fibrosis [12] and Young's syndrome [10]) are not associated with an increased occurrence of otitis media, while other mucosal diseases (immotile cilia syndrome [17] and vitamin A deprivation in rats [5]) apparently are associated with otitis media., We suspect allergic rhinitis correlates with the more severe cases of otitis media: e.g. patients requiring surgery for the otitis [11]. From our data, however, the possible aggravating role of allergic airway disease in otitis patients who came to myringtomy-tubes cannot be determined.
Implications The minimal association of allergic rhinitis with otitis media in these children may serve to emphasize the musculoskeletal eustachian tube difference as the important etiologic factor for otitis media [4,23]. The eustachian tube difference manifests
33 kPa Nasopharynx
-10 -12 t -14
~-MiddleEar
J
IAI
(B) IC)
|
Time (sec) Fig. 2. Pressure changes during a sniff. (Adapted, with permission, from Magnuson and Falk, ref. 14. p. 663, Fig. 4.) "Simultaneous pressure recordings from the nasopharynx and middle ear obtained" in a person with relative eustachian tube closing failure. " T h e arrow indicates that the sniff-induced high negative pressure was released by the investigator". See Fig. 3 for hypothesized access of airborne allergen into the eustachian tube at time C.
primarily by poor ventilation from nasopharynx to middle ear, by allowing reflux from nasopharynx to middle ear, and by allowing sniff-induced high negative pressure in the middle ear (Fig. 2). We hypothesize that allergic rhinitis exacerbates eustachian tube malfunction, and enhances the occurrence of otitis media in patients who have a musculoskeletally different eustachian tube. Such eustachian tube could allow access of inhalent allergen, or inhalant irritant, to the mucosa of the eustachian tube during sniff relaxation (Fig. 3). This hypothesized mechanism of the role of allergy in the etiology and pathogenesis of otitis media has been mentioned [4], and this report provides epidemiologic substantiation. The eustachian tube difference is (A)
(B)
(C~
(.' Fig. 3. Hypothesized schematic illustration of a person with relative eustachian tube closing failure: before sniffing (A), during sniffing (B), and during sniff relaxation (C). At rest (A), the eustachian tube is closed, the nasopharyngeal pressure is essentially equal to the middle ear pressure, and the tympanic membrane is in normal position. During peak sniffing (B), the eustachian tube is open (perhaps by active muscle contraction), the nasopharyngeal pressure is less than atmospheric pressure but equal to middle ear pressure, and the tympanic membrane is retracted medially. When the eustachian tube is almost closed during relaxation from a sniff (C), nasopharyngeal pressure is approaching atmospheric pressure, middle ear pressure is less than both nasopharyngeal and atmospheric pressure, and the tympanic membrane is not quite so retracted. Aspiration of air and airborne allergen into the eustachian tube is hypothesized to occur during relaxation from a sniff when the pressure gradient is from nasopharynx to middle ear.
34
probably genetically determined, but allergic airway disease is largely environmentally determined.
Acknowledgements Dr. Melvin H. Goodwin gave invaluable aid and encouragement. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the Indian Health Service.
References 1 Anderson, H.R., Bailey, P.A. and Bland, J.M., The effect of birth month on asthma, eczema, hayfever, respiratory symptoms, lung function, and hospital admissions for asthma, Int. J. Epidemiol., 10 (1981 ) 45-51. 2 Bernstein, J.M., Lee, J., Conboy, K., Ellis, E. and Li, P., The role of IgE mediated hypersensitivity in recurrent otitis media with effusion, Amer. J. Otol., 5 (1983) 66-69. 3 Bierman, D.W., Pierson, D.S. and Donaldson, J.A.. Diseases of the nose. In D.W. Bierman and D.S. Pearlman (Eds.), Allergic Diseases of Infancy, Childhood and Adolescence, W.B. Saunders, Philadelphia, 1980, p. 514. 4 Bluestone, C.D., Eustachian tube function: physiology, pathophysiology, and role of allergy in pathogenesis of otitis media, J. Allergy Clin. lmmunol., 72 (1983) 242-251. 5 Chole, R.A., Squamous metaplasia of the middle ear mucosa during vitamin A deprivation, Otolaryngol. Head Neck Surg., 87 (1979) 837-844. 6 De, P.R.. Secretory otitis media and allergic rhinitis, J. Laryngol. Otol., 94 (1980) 185-189. 7 Dodge, R.R. and Burrows, B., The prevalence and incidence of asthma and asthma-like symptoms in a general population sample, Amer. Rev. resp. Dis. 122 (1980) 567-575. 8 Goodwin, M.H., Shaw, J.R. and Feldman, C.M., Distribution of otitis media among four Indian populations in Arizona, Publ. Hlth. Rep. (Wash.), 95 (1980) 589-594. 9 Handelsman, D.J., Conway, A.J., Boylan, L.M. and Turtle, J.R., Young's syndrome: obstructive azoospermia and chronic sinopulmonary infections, N. Engl. J. Med., 310 (1984) 3-9. 10 Johnstone, D.E., Some aspects of the natural history of asthma, Ann. Allergy, 49 (1982) 257-264. 11 Kraemer, M.J., Richardson, M.A., Weiss, N.S., Furukawa, C.T., Shapiro, G.G., Pierson, W.E. and Bierman, C.W., Risk factors for persistent middle-ear effusions, J. Am. Med. Assoc., 249 (1983) 1022-1025. 12 Kramer, R.I., Otorhinolaryngologic complications of cystic fibrosis, Otolaryngol. Clin. North Am., 10 (1977) 205-208. 13 Luoma, R., Koivikko, A. and Viander, M., Development of asthma, allergic rhinitis and atopic dermatitis by the age of five years, Allergy, 38 (1983) 339-346. 14 Magnuson, B. and Falk, B., Diagnosis and management of eustachian tube malfunction, Otolaryngol. Clin. North Am., 17 (1984) 659-671. 15 Matthews, K.P., Respiratory atopic disease, J. Amer. Med. Assoc. 248 (1982) 2587-2610. 16 McMahan, J.T., Calenoff, E., Croft, D.J., Barenholtz, L. and Weber, L.D., Chronic otitis media with effusion and allergy: modified RAST analysis in 119 cases, Otolaryngol. Head Neck Surg., 89 (1981) 427-431. 17 Mossberg, B., Immotile-cilia syndrome: clinical features, Eur. J. Resp. Dis., Suppl 118, 63 (1982) 111-115. 18 Ruokonen, J., Halopainen, E., Palva, T. and Backman, A., Secretory otitis media and allergy: with special reference to the cytotoxic leukocyte test, Allergy, 36 (1981) 59-68. 19 Shambaugh, G.E., Panel discussion: serous effusion of the middle ear, Laryngoscope, 85 (1975) 128-139.
35 20 Shaw, J.R., Goodwin, M.H., Feldman, C.M. and Kingsolver, A.E., Otitis Media Project Quaterly Report, Department of Family and Community Medicine, University of Arizona Health Sciences Center, Tucson, Arizona, Oct.-Dec. 1982. 21 Shaw, J.R., Todd, N.W., Goodwin, M.H. and Feldman, C.M., Observations on the relation of environmental and behavioral factors to the occurrence of otitis media among Indian children, Publ. Hlth. Rep. (Wash.), 96 (1981) 342-349. 22 Sievers, M.L. and Fisher, J.R., Diseases of North American Indians. In H. Rothschild (Ed.): Biocultural Aspects of Disease, Academic Press, New York, 1981, p. 234. 23 Todd, N.W., Otitis media and eustachian tube caliber, Acta Oto-laryngol. (Stockh.), Suppl. 1, 404 (1983) 1-17.
27
Elsevier
P O R 00327
Allergic airway disease and otitis media in children N. W e n d e l l T o d d a n d Clyde M. F e l d m a n Department of Otorhinolar~'ngology and Communication Sciences. Phoenix Indian Medical Center, 421'2 N. 16th Street. Phoenix, A Z 85016, and Department of Family and Community Medicine. Universit); of A rizona Medical Center. Tucson, A Z 85724 (U.S.A.) (Received October 15th, 1984) (Revised May 14th, 1985) (Accepted June 8th, 1985)
Key words: allergic rhinitis - asthma - eustachian tube - otitis media
Summary The occurrence of allergic rhinitis, asthma and otitis media was examined in 395 Indian children living on two separate reservations in Arizona. The children were followed from birth to age 5 years in a study of otitis media. On retrospective review of medical records, 45% of the children at Parker had a clinical diagnosis of allergic airway disease, in contrast to only 6% at San Carlos. At each site, about 55% had recurring otitis media in infancy; of these otitis-prone infants, 40% at Parker and 36% at San Carlos persisted to have 3 or more episodes of otitis media after age 2 years. The only allergic airway disease correlate with otitis media was allergic rhinitis in children age 2-4 years.
Introduction
The relation of allergic airway disease to otitis media is controversial, with some [19,16] endorsing a very strong (90%) cause-effect relationship, and others [4,6,18] suggesting a much smaller relationship. With some exceptions [11], studies endorsing a relationship are not randomized or controlled, and do not consider treatment modalities other than allergic [2]. We present an epidemiologic study involving patients selected for having neither allergic airway disease not otitis media. Correspondence: N.W. Todd. Present address: Emory University School of Medicine. 1365 Clifton Road. Atlanta, G A 30322, U.S.A.
0165-5876/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
28
Background of the study A prospective study from birth of native American Indian children living on 4 separate reservations in Arizona began in 1974 to identify environmental correlates of the high occurrence of otitis media. No environmental correlate of otitis media in infancy was found [21]. The natural history of otitis media has been documented in these children: an infant with two or more clinical encounters for separate occurrences of otitis media is 'high risk' for having subsequent episodes of otitis media in the first two years of life [8]. Most of the initial attacks of acute suppurative otitis media occur during the first year of life, and most subsequent attacks occur within 4 months of a prior attack. A child aged 2 - 4 years, with 3 or more clinical encounters for separate occurrences of otitis media, is considered to have 'persistent' otitis media problems. These categories are epidemiologically sound whether the specific clinical diagnosis at a particular time is acute suppurative otitis media, chronic otitis media (tympanic membrane perforation for more than 3 weeks), or middle ear effusion. The winter seasonal exacerbation of otitis media problems is the same for each of the diagnostic categories, and for patients living at each of the 4 reservations. Zero or only one clinical encounter for otitis media in the initial two years of life associates with a 9570 likelihood of a child not having 'persistent' otitis [20].
Materials and Methods Review of the cohorts at the Colorado River Indian Reservation, at Parker in western Arizona identified 160 patients as having had essentially continuous medical care at the local United States Public Health Service Indian Hospital for the first 5 years of life. Each patient's medical record was reviewed for the date of encounter for any of the following physician-made diagnoses: 'allergic rhinitis', 'hay fever', 'reactive airway disease', and 'asthma'. Additionally, each record was searched regarding eosinophilia (not attributable to parasitic infection) on peripheral blood smear, serum IgE, nasal smear for eosinophils, skin test documentation of allergic airway disease, and allergist's diagnostic assessment. The data of children at another otitis media project site were similarly studied: San Carlos, an Apache reservation in eastern Arizona. Two hundred and thirty-five children were identified as having had presumably continuous medical attention at the U.S.P.H.S. Indian Hospital there. Standard diagnostic criteria for otitis media were used [8,21]. Generally accepted diagnostic criteria for allergic airway conditions are assumed. Some uniformity of allergic airway diagnoses may have been afforded by the involvement at these study sites of just one otolaryngologist [NWT]. In addition to providing telephone consultation to physicians on these reservations and seeing the patients in Phoenix for consultation and surgery, he made approximately monthly visits to each reservation's hospital from July 1974 to June 1984. These 'field clinics' provided an opportunity for patients to be seen in consultation, for the primary care physicians to confer with the otolaryngologist, and for the otolaryngologist to monitor the quality of care (including documentation in the patient medical records).
29 F o r the p u r p o s e s of this study, hay fever a n d allergic rhinitis d i a g n o s e s were g r o u p e d a n d c o n s i d e r e d ' a l l e r g i c rhinitis'. Similarly, a s t h m a a n d reactive a i r w a y d i s e a s e were g r o u p e d a n d c o n s i d e r e d ' a s t h m a ' . Statistical a s s e s s m e n t was p e r f o r m e d with the x2-test.
Results T h e p a t t e r n s of o c c u r r e n c e of otitis m e d i a were strikingly similar at the two r e s e r v a t i o n s ( T a b l e I). Before two years of age, a b o u t 55% of the c h i l d r e n had at least two s e p a r a t e clinical e p i s o d e s of otitis media. A t Parker, 40% of these o t i t i s - p r o n e i n f a n t s p e r s i s t e d to have 3 or m o r e e p i s o d e s in the next 3 years; at San C a r l o s , 36%. Likewise, the ' n o t high risk' followed b y ' p e r s i s t e n t ' otitis p a t t e r n was similar: 5.6% of the P a r k e r group, 5.1% of the San C a r l o s group. (These ' n o t high risk' then ' p e r s i s t e n t ' p a t i e n t s p r e s u m a b l y h a d silent otitis m e d i a d u r i n g the first two y e a r s o f life.) T h e r e c o r d i n g o f allergic a i r w a y disease o c c u r r e n c e was m a r k e d l y different (X 2 = 85, P < 0 . 0 0 1 ) at the two s t u d y sites: 45% at Parker, b u t o n l y 6% at San C a r l o s ( T a b l e II). A t Parker, 22 of the 160 c h i l d r e n were labelled as having a s t h m a ,
TABLE I PATTERNS OF OTITIS MEDIA AT PARKER AND SAN CARLOS * High risk, two or more clinical encounters for separate episodes of otitis media in the first two years of life; persistent, 3 or more clinical encounters for separate episodes of otitis media in a child age 2-4 years. Otitis media pattern
Parker
High risk. persistent High risk, not persistent Not high risk, but persistent Not high risk. not persistent Total
San Carlos
Total
35 53 9 63
46 80 12 97
81 133 21 160
160
235
335
* No significant difference.
TABLE I1 ALLERGIC AIRWAY DISEASE AT PARKER AND SAN CARLOS X2
= 85, P < 0.001.
Allergic airway disease Yes No Total
Parker
San Carlos
Total
73 87
14 221
87 308
160
235
395
30 T A B L E Ill A L L E R G I C A I R W A Y DISEASE VERSUS OTITIS M E D I A P A T T E R N IN C H I L D R E N LESS T H A N AGE 5 YEARS AT PARKER * Otitis media pattern
Allergic airway disease
High risk, persistent High risk, not persistent Not high risk, but persistent Not high risk, not persistent Total
Diagnosed
Not diagnosed
12 28 6 27
23 25 3 36
Total 35 53 9 63
'73
87
160
* No significant difference.
on 57 separate occasions. The median age for initial encounter for asthma was 28 months, with a range of 1-59 months. For allergic rhinitis, the total n u m b e r of encounters for the 69 children so diagnosed, at one time or another, was 204. The median age for initial encounter for allergic rhinitis was 12.5 months. Of the 22 children labelled as having asthma, 19 also had an allergic rhinitis diagnosis. Of the children considered clinically to have allergic airway disease, 26% (19/73) had additional information (4 had more than one positive supporting test) to support the diagnosis: 14 had eosinophilia > 5% on peripheral blood smear on at least one occasion; 3 had at least one elevated (for age) serum IgE, 2 had more than 20% eosinophils on at least one smear of nasal mucus, 2 had positive skin test responses to inhalent allergens, and 2 received an allergist's diagnosis without benefit of additional tests. Of the 14 San Carlos children diagnosed as having allergic airway disease, none had IgE, nasal or peripheral smear eosinophil data, nor skin testing to inhalant allergens, to support the diagnosis. Nine had asthma, the inverse of the allergic rhinitis to asthma ratio of diagnoses at Parker. If the diagnoses of allergic rhinitis were understated at San Carlos, and if the asthma diagnoses were valid, and if the true cumulative ratio of allergic rhinitis to asthma were 3 : 1 (the ratio found at T A B L E IV A L L E R G I C R H I N I T I S VERSUS OTITIS M E D I A P A T T E R N IN C H I L D R E N A G E 2 - 4 Y E A R S A T PARKER X 2 = 5.65, P < 0.02. Allergic rhinitis Diagnosed
Not diagnosed
Total
Persistent otitis Not persistent
22 33
22 83
44 116
Total
55
105
160
31 40-
t,-
35"
oo ¢ uJ
30.
u." "6_ 1-
asthma • allergic rhinitis • otitis media •
" t
,//
\I
20.
/ ',,,
15lo-
,/' ~ll \ I \;
O-
i~ ,' ""
'•-J ~ ' t
,,,' "" )k,,
/,i .... ,--.-at
Ii
A g e In M o n t h s
Fig. 1. Age distribution o f first encounters for allergic rhinitis, asthma, and otitis media among 150 Indian children at Parker.
Parker, and reported elsewhere [13,15]), then 32 children at San Carlos could be considered allergic. Even if all this were so, the allergic airway disease occurrence would still be markedly different (X 2 = 47, P < 0.001) than at Parker. An association of allergic airway disease with otitis media was difficult to identify (Table III). Multiple analyses of number of clinic visits for allergic airway diseases versus otitis media revealed only one association: children age 2 - 4 years, at Parker, with one or more clinical encounters for allergic rhinitis, were more likely (X 2 = 5.65, P < 0.02) to have 3 or more clinical encounters for otitis media (Table IV). The ages of first clinical encounter for asthma and allergic rhinitis are older than that for otitis media (Fig. 1). In contrast to the winter season increase of otitis media, neither allergic rhinitis nor asthma had a statistically significant seasonal trend. No birth month association with subsequent allergic airway disease or otitis media was discernible. Although the otitis media rates and patterns were similar in these two populations, the allergic airway disease rates were quite different. Only in children who had otitis media recurringly in infancy, did allergic rhini.tis subsequently correlate with otitis media. Children fortunate enough to have escaped two or more bouts of otitis media in infancy, did not have significant otitis problems in the next 3 years, even if allergic rhinitis became a health problem prompting repeated physician visits. Discussion
The present study suggests that the relationship between allergic airway disease and otitis media is weak. Our data are more likely to be accurate than parent recall
32 studies [7,11]. However, some qualifications limit the interpretation of our results. The diagnosis of allergic rhinitis is often difficult in infancy. A number of different physicians attended these children, and the criteria for allergic airway disease diagnosis were not standardized. Perhaps the involvement of the same otolaryngologist prompted some uniformity of diagnoses. Only 26% of the allergic airway patients at Parker, and none at San Carlos, had support for the diagnosis beyond the history and physical examination by the general physician. The variables of exposure to household pets, tobacco, and other inhalent allergens and irritants are unknown. Patient access to medical services, use of the services, and quality of the services at the two facilities are presumably equal. Lastly, the appropriateness of extrapolating these findings to other populations is unknown. The concordance of allergic rhinitis and asthma has been noted by others [3,13]. Our finding of a 3 : 1 ratio of cumulative occurrence, in the first 5 years of life, of allergic rhinitis to asthma at Parker is similar to that reported by others [13A5] in diverse geographies. As would be expected [1], for children exposed to essentially year-round inhalant allergens, neither birth month nor season correlated with allergic airway diagnoses. Why were allergic airway problems so common in our Parker group, in contrast to our San Carlos group and elsewhere [3,13]? The question is especially interesting because "allergic (extrinsic) asthma and other atopic diseases occur less often in native Americans than whites" [22]. We think the explanation of Johnstone [10], in addressing the occurrence of asthma in developed versus developing countries, is applicable: environmental rather than purely genetic factors explain the differences. The reservation at Parker, in contrast to San Carlos, is in an agriculturally highly developed irrigated valley. The Indian population at Parker is a mix of about 5% Chemehuevi, 40% Mohave, 20% Navajo, 20% Hopi, and 15% other tribes. In contrast, San Carlos Apaches are an essentially homogeneous genetic group. However, no attempt was made to assess the degree of Indian 'blood' for the individual patients of our study groups. The finding that clinical allergic airway disease epidemiologically did not correlate well with otitis media is not surprising. Some mucosal diseases (cystic fibrosis [12] and Young's syndrome [10]) are not associated with an increased occurrence of otitis media, while other mucosal diseases (immotile cilia syndrome [17] and vitamin A deprivation in rats [5]) apparently are associated with otitis media., We suspect allergic rhinitis correlates with the more severe cases of otitis media: e.g. patients requiring surgery for the otitis [11]. From our data, however, the possible aggravating role of allergic airway disease in otitis patients who came to myringtomy-tubes cannot be determined.
Implications The minimal association of allergic rhinitis with otitis media in these children may serve to emphasize the musculoskeletal eustachian tube difference as the important etiologic factor for otitis media [4,23]. The eustachian tube difference manifests
33 kPa Nasopharynx
-10 -12 t -14
~-MiddleEar
J
IAI
(B) IC)
|
Time (sec) Fig. 2. Pressure changes during a sniff. (Adapted, with permission, from Magnuson and Falk, ref. 14. p. 663, Fig. 4.) "Simultaneous pressure recordings from the nasopharynx and middle ear obtained" in a person with relative eustachian tube closing failure. " T h e arrow indicates that the sniff-induced high negative pressure was released by the investigator". See Fig. 3 for hypothesized access of airborne allergen into the eustachian tube at time C.
primarily by poor ventilation from nasopharynx to middle ear, by allowing reflux from nasopharynx to middle ear, and by allowing sniff-induced high negative pressure in the middle ear (Fig. 2). We hypothesize that allergic rhinitis exacerbates eustachian tube malfunction, and enhances the occurrence of otitis media in patients who have a musculoskeletally different eustachian tube. Such eustachian tube could allow access of inhalent allergen, or inhalant irritant, to the mucosa of the eustachian tube during sniff relaxation (Fig. 3). This hypothesized mechanism of the role of allergy in the etiology and pathogenesis of otitis media has been mentioned [4], and this report provides epidemiologic substantiation. The eustachian tube difference is (A)
(B)
(C~
(.' Fig. 3. Hypothesized schematic illustration of a person with relative eustachian tube closing failure: before sniffing (A), during sniffing (B), and during sniff relaxation (C). At rest (A), the eustachian tube is closed, the nasopharyngeal pressure is essentially equal to the middle ear pressure, and the tympanic membrane is in normal position. During peak sniffing (B), the eustachian tube is open (perhaps by active muscle contraction), the nasopharyngeal pressure is less than atmospheric pressure but equal to middle ear pressure, and the tympanic membrane is retracted medially. When the eustachian tube is almost closed during relaxation from a sniff (C), nasopharyngeal pressure is approaching atmospheric pressure, middle ear pressure is less than both nasopharyngeal and atmospheric pressure, and the tympanic membrane is not quite so retracted. Aspiration of air and airborne allergen into the eustachian tube is hypothesized to occur during relaxation from a sniff when the pressure gradient is from nasopharynx to middle ear.
34
probably genetically determined, but allergic airway disease is largely environmentally determined.
Acknowledgements Dr. Melvin H. Goodwin gave invaluable aid and encouragement. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the Indian Health Service.
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