Upper Airway Disorders

(1)

Upper

Airway

Disorders

PATHOPHYSIOLOGY

NASOPHARYNGEAL FLORA IN THE FIRST THREE YEARS OF LIFE IN NORMAL AND OTITIS-PRONE

CHILDREN

Faden H, Brodsky L, Waz MJ, Stanievich J, Bernstein J,

Ogra P. Ann Otol Rhinol Laryngol. 1991;100:612-615

Purpose of the Study

The study was conducted to establish the types of

middle ear bacterial pathogens found in the

na-sopharyngeal region of a group of normal children.

Study Population

A total of 110 demographically similar children

aged 2 months to 3 years, who lived in the Greater

Buffalo, New York, area, were enrolled in a 3-year

prospective study of the natural history of otitis me-dia as it relates to the nasopharyngeal bacterial flora.

As the study progressed the group was divided into

otitis-prone (OP) and non-otitis-prone (NOP)

chil-dren.

Methods

The children had at least one visit every 3 months

for the evaluation of the nasal passages and ears.

They were examined by the same group of

investi-gators for sick visits. At each visit, whether sick or well, cultures from the nasopharynx were obtained.

Findings

The OP children, even when well, were found to

carry middle ear pathogens, Streptococcus pneumo-niae, Moraxella catarrhalis, or nontypeable Haemophilus influenzae, at a rate statistically higher than the NOP group. When they were ill with a respiratory illness,

the recovery rate of the same pathogens was again

found to a greater degree in the OP children than the

NOP ones. Of interest, H influenzae type B was not

isolated in any nasopharyngeal culture.

Conclusions

The study is in general agreement with other pub-lished accounts, but the reason for this chronic

car-riage rate of middle ear pathogens in OP children

remains unknown.

Reviewer’s Comments

We have all encountered those unfortunate

chil-dren who must feel like “Pig Pen” in “Peanuts.” To

refresh your memory, he is the kid who always is pictured walking in a cloud of dust.

THAD H. Joos, MD

Grosse Pointe Woods, MI

HISTAMINE-CONTAINING CELLS OBTAINED

FROM THE NOSE HOURS AFTER ANTIGEN

CHALLENGE HAVE FUNCTIONAL AND

PHENOTYPIC CHARACTERISTICS OF BASOPHILS

Iliopoulos 0, Baroody FM, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM. J Immunol. 1992;148: 2223-2228

The authors sought to identify whether the cells

recovered after nasal allergen challenge and which

stain with Alcian blue are basophils or mast cells.

Methods

Allergic subjects were intranasally challenged with

increasing doses of ragweed or grass pollen extracts.

Approximately 24 hours after antigen challenge, the

subjects returned to the laboratory for nasal leuko-cyte collection and processing. Multiple nasal

lay-ages were performed to increase the yield of the na-sal cellular infiltrate. The cells obtained during

lavage were isolated for degranulation studies and

analysis of surface antigens and viability.

Findings

Alcian blue-stained cells are commonly found in

nasal lavages during the late-phase response follow-ing antigen challenge. By light microscopy criteria,

large numbers of these cells appeared to be

baso-phils. The average histamine content of these cells is similar to that reported for peripheral basophils. Dual-color immunofluorescence and flow cytometry analysis of the recovered nasal cells show that the vast number of these Alcian blue-staining cells con-tain IgE and co-express CD-18, a leukocyte marker

not expressed by mast cells. These nasal cells

consis-tently demonstrated high levels of spontaneous his-tamine release. The characteristics of the histamine

release and the nature of the cellular surface markers

found on Alcian blue cells recovered during the late

phase response strongly suggest that these cells are basophils and not mast cells.

Reviewer’s Comments

The role of the basophil in the allergic reactions, both early and late, has previously been suggested by the presence of local mediators. We are very familiar with eosinophils having specific chemoattractants that amplify their transmigration. The exact

media-tors that attract basophils need to be identified. The

presence of basophils in the late-phase response may

also have a potential bearing on therapy, as topical

anti-inflammatory agents, such as cromolyn sodium

or corticosteroids, may have differential effects on basophil function or effect on the release of basophil mediators. This is an exciting area of investigation,

both at the basic science and clinical levels.

(2)

IMPLICATION OF SURFACTANT APOPROTEIN IN

OTITIS MEDIA WITH EFFUSION

Kobayashi K, Kuroki Y, Kataura A, Aldno T, Yamanaka N. Ann Otol Rhinol Laryngol. 1991;100:835-837

To determine whether the presence of surfactant apoprotein (SAP) in the aspirates of middle ear

effu-sion correlates with the ongoing ear problem, and also the relationship of SAP to chronic sinusitis in the

same group. Study Population

Middle ear effusion samples were obtained from

115 children aged 3 through 14 years who demon-strated chronic otitis media with effusion. These

same children, after appropriate therapy, were

fol-lowed until recovery occurred. Methods

The aspirates were classified as serous, purulent,

mucoid, or Hyperviscous. The presence and levels of

SAP were determined by suitable immunoassay

techniques.

Findings

Children with detectable SAP, regardless of quan-tity present, recovered in a significantly shorter time (17.3 months vs 26.2 months). In those children with

detectable SAP, surfactant apoprotein was found

more often in the serous fluid group (81.2%) than the

hyperviscous type (13.6%). Chronic sinus infection

was found to occur more often in the SAP-negative

group. Conclusions

Surfactant does lower surface tension and its pres-ence in the middle ear may well favorably influence

eustachian tube function, thereby reducing the

accu-mulation of fluid. Reviewer’s Comments

The neonatologist is now using surfactant

replace-ment therapy with encouraging results. The

corn-pound may also find a place in the treatment of

middle ear effusion.

THAD H. Joos, MD

Grosse Pointe Woods, MI

LYMPHOCYFE SUBSETS IN IMMUNE-MEDIATED

OTITIS MEDIA WITH EFFUSION

Takahashi M, Kanai N, Watanabe A, Oshima 0, Ryan #{192}Y.

Eur Arch Otorhinolaryngol. 1992;249:24-27

The purpose of the study was to examine whether

or not T-cell subsets play an important role in

im-mune-mediated otitis media by employing a mouse

model. The kinetics of immunocytes in the middle

ear (ME) and the eustachian tube were investigated

immunohistochemically after immunostimulation of

the ME with keyhole limpet hemocyanin (KLH). The

rationale behind the study is that it has been shown

experimentally and clinically that the ME has the

capacity to mount an immune response which

in-dudes a mucosal component. Additionally, helper

T-cells in mucosa-associated lymphoid tissue help to

switch plasma cell isotype to IgA, which is the most

important immunoglobulin class in mucosal

immu-nity.

Eighteen adult BALB/C mice.

Methods

Antibodies against munine macrophages and

granulocytes, helper T-cells, suppressor T-cells,

im-munoglobulins, secretory component, and KLH were

used. Animals were immunized subcutaneously

with KLH.

Findings

The ME exhibited a substantial immune response,

whereas the response of the eustacian tube was

mi-nor and was associated with a secondary ME

im-mune response. After KLH challenge, an effusion

with an extensive infiltration of inflammatory cells,

predominantly macrophages, granulocytes,

IgG-pos-itive cells, and 1gM-positive cells, was observed at

day 1 and 3 in the ME, and disappeared by day 7.

Within the ME mucosa, a large number of cells were

observed at days 1 and 3, peaking at day 7.

Granu-locytes and macrophages were the predominant cell

type followed by helper T-cells, IgG-positive cells, IgA-positive cells, and then 1gM-positive cells in the mucosa. Suppressor T-cells were rarely detected, and

secretory component was present within the ME

ep-ithelial cells from day I to 14.

Conclusions

The authors conclude that (1) the majority of infil-trating cells in the ME cavity originate from

circula-tion, (2) the ME mucosa has an excellent capacity to

mount a strong immune response by accumulating

immune cells for antigen processing and antibody

production, and (3) the elimination of antigen

ap-pears to be the most important factor for turning off

the immune response. Thus, the elimination of KLH

shut the response down.

This study suggests that the immune reaction, at

least in their model, might return to a quiet state by

eliminating antigen rather than from suppressor

T-cells. In a human this might imply that if one can more easily eliminate bacteria and/or bacteria

anti-gens or possibly allergens from the ME, one could

eliminate or abort an ME effusion and disease proc-ess. Perhaps in humans the more aggressive

elimina-tion of bacteria antigens or bacteria might diminish

the chronicity of ME effusions, and, possibly,

evacu-ating the fluid may be of some benefit, with or

with-out PE tubes.

Giu S. RAcHELEFSKY, MD

(3)

DEMONSTRATION OF INTERLEUKIN 6 IN MIDDLE

EAR EFFUSIONS

Yellon RI, Leonard G, Marucha P, Sidman

J,

Carpenter R,

Burleson

J,

Carlson

J,

Kreutzer D. Arch Otolaryngol Head Neck Surg. 1992;118:745-748

These authors in a previous study have demon-strated significant levels of interleukin-1 (IL-i), IL-2,

tumor necrosis factor, and interferon gamma (IFN-g) in significant number of middle ear effusions (MEEs)

from children with otitis media with effusion (OME).

In this study, they looked at the levels of IL-6 in

MEEs from children with OME.

The study population included 25 children with

OME, who underwent placement of PE tubes.

Methods

Thirty-nine MEEs were collected from 25 children

whose average age was 4.3 years. Twenty effusions were serous, 5 seromucoid, and 14 mucoid. Assays for IL-6 were performed with commercially available

enzyme-linked immunosorbent assay kits.

Findings

There were significant levels of IL-6 in 36% of the

39 MEEs. The mean level was 173 ± 75 pg/mg. The

levels were not correlated with blood in the effu-sions. The levels were inversely correlated with age

such that levels of IL-6 were observed to increase

along a continuum.

Conclusions

N The authors conclude that these results, along with

those of their other studies, indicate that IL-2, IL-3, and IL-6 may act synergistically to help clear bacteria from the middle ear, and that is why IL-6 was found in higher amounts. Activities of IL-6 indude

simula-tion of bone erosion and production of antibodies and fever. The authors believe that IL-I and 11-6 may be important regulators of immune response in the early stages of otitis media with effusion.

Middle ear disease is becoming more complicated and much more immunologically interesting. These authors provide some evidence that lymphocyte

cy-tokines may be involved in the body’s response to

middle ear disease in children. For obvious reasons, more studies need to be done and not just on children

whose ear disease has progressed to the point of

needing PE tubes. Perhaps in the future we will be

treating this disease with immune modulators and not just with antibiotics.

G&iv S. RACHELEPSKY, MD

Los Angeles, CA

TREATMENT

INFECTIONS OF THE EARS, NOSE, AND THROAT

IN CHILDREN WITH PRIMARY

IMMUNODEFICIENCIES

Haddad

J

Jr, Brager R, Bluestone CD. Arch Otolaryngol Head Neck Surg. 1992;118:138-141

Children who suffer from primary immune

defi-ciencies have long been thought to be more

suscep-tible to infections of the ears, nose, and throat due to unusual or resistant organisms. This was a retrospec-tive chart review at Children’s Hospital of Pittsburgh

over a 10-year period to determine the types and

frequency of infections of the ears, nose, and throat,

and the bacteriologic findings from cultures of the

sinuses, ears, and head and neck abscesses, when

obtained from children with immune deficiency.

Seventy-five children with primary

immunodefi-ciencies.

Methods

This was basically chart review.

Findings

Of 55 patients with B-cell deficiency, 15 had IgA

deficiency, 14 had hypogammaglobulinemia, 10 had

common variable immune deficiency, and 5 had IgG subclass deficiency. There were 4 with combined B- and T-cell problems, 5 with T-cell problems

(DiGeorge syndrome), 3 with complement pathway defect, and 7 with a phagocytic defect (chronic gran-ulomatous disease). Of the 75, 60 (80%) had infec-tions of the ear, nose, and throat. A total of 34 cultures were obtained from 20 patients; #{189}were positive, with Haemophilus influenzae and Staphylococcus aureus

the only pathologic organisms obtained from the

ears. Sinus cultures revealed Streptococcus pneumoniae in 5, H influenzae in 4, Moraxella catarrhalis in 4, and Streptococcus pyogenes in 1. It appeared from their data that history of recurrent or chronic otitis media,

sinusitis, or both were very common in the

immune-deficient patient, predominantly in those with B-cell

problems. Patients with DiGeorge syndrome were

relatively free of ear and sinus problems.

Conclusions

CultUres from most of these patients showed the

majority of organisms commonly seen in ear and

sinus infections, even in non-immune-deficient

pa-tients.

This study demonstrates that children with pri-mary immune deficiencies, especially those with

B-cell problems who require hospitalizations, and

who have infections of the ear, nose, and throat, have

(4)

community-acquired bacteria. Therefore, the treatment may be

directed to common organisms causing these

infec-tions, and one should not be concerned about

eso-teric or unusual organisms.

Gi S. R Ipsi(y, MD

Los Angeles, CA

FOLLOW-UP OF ENDOSCOPIC SINUS SURGERY

ON CHILDREN WITH CYSTIC FIBROSIS

Cuyler JD. Arch Otolaryngol Head Neck Surg. 1992;118:

505-506

This study was undertaken to determine whether

the sinus disease in children with cystic fibrosis may

be improved by endoscopic surgery when compared

with control patients and to evaluate the degree of

recurrence or persistence of sinus disease 2 or more

years after surgery. The authors discussed the fact

that computed tomographic (CT) scans of the sinuses are universally abnormal in children with cystic

fi-brosis, although all do not have symptoms from the sinus disease.

Ten children with proven diagnosis of cystic

fibro-sis were evaluated; seven had polyposis and sinusi-tis, and five of the seven had symptoms consistent

with sinusitis. Three children with cystic fibrosis, the control patients, had no chronic nasal symptoms

con-sistent with sinusitis. All children had cough, but this was thought to be due to pulmonary disease.

Methods

Patients all underwent endoscopic surgery, having nasal polypoectomies, enlargement of the natural maxillary antra, and at least a limited ethmoidec-tomy. Patients were seen on a 3- to 6-month basis, for at least 2 years. Additional CT scans of the sinuses were done at 2 years.

Findings

All patients and parents believed nasal obstruction was improved, and the five with sinus symptoms

believed that their condition was improved. Two of

the surgical patients have required subsequent

sur-gery for recurrent nasal polyps, one at 2#{189}years and another at 3 years after the initial surgery.

Conclusions

The data suggest, at least in this small group, that endoscopic sinus surgery is not a cure for sinus dis-ease in these children, but may be helpful in

control-ling upper airway symptoms.

Although this study is positive for surgical inter-vention for the cystic fibrosis patient with upper air-way disease, it would have been very helpful if the author also had looked at the patients’ pulmonary

disease to determine whether that was also improved

by sinus surgery. In my own anecdotal experience, patients with cystic fibrosis, if they have significant

hyperreactivity, do improve their lower airway dis-ease by having endoscopic surgery of their paranasal

sinus.

GARY S. RACHELEFSKY, MD

Los Angeles, CA

FOLLOW-UP OF ENDOSCOPIC SINUS SURGERY

ON CHILDREN WITH CYSTIC FIBROSIS

Cuyler JP. Arch Otolarijngol Head Neck Surg. 1992;118:

505-506

There were 10 patients aged 4 through 19 years

with proven cystic fibrosis. Seven had polyposis; five of those had symptoms consistent with sinusitis. The

three other children lacked symptoms of nasal

ob-struction or sinusitis and served as controls.

Methods

All 7 symptomatic children had endoscopic

polypectomies and enlargement of maxillary antra.

All 10 children were followed over the next 3 years.

At 3 years they had additional computed

tomo-graphic (CT) scans and completed questionnaires

concerning satisfaction with the results of the sur-gery.

Findings

All 10 children had CT findings of pansinusitis

initially and 3 years later-even the 7 who had had surgery. Yet all 7 of the surgically treated patients (and their families) reported subjective symptomatic

improvement in obstructive and sinus symptoms. All

would be willing to undergo the procedure again, if

necessary.

Removing the obstructing polyp helped the

symp-toms of obstruction. It remains unclear why the

si-nusitis symptoms were improved since the CT scans continued to show pansinusitis. As the author points

out, the main problem is one of mucoviscidosis and

surgery does not correct that.

ALLEN T. SIEGEL, MD

Dallas, TX

CLINICAL EVALUATION OF TRIAMCINOLONE

ACETONIDE NASAL AEROSOL IN CHILDREN

WITH PERENNIAL ALLERGIC RHINITIS

Welch MJ, Bronsky EA, Grossman

J,

Shapiro GG, Tint-elman DG, Garcia JD, Gillen MS. Ann Allergy. 1991;67:

493-498

Purpose of the Study

Triamcinolone acetonide aerosol (TAA), a topical

(5)

Lower

Airway

Disorders

to be highly effective in the treatment of seasonal and

perennial allergic rhinitis (PAR) in adults. The

pur-pose of this study is to evaluate the efficacy and

safety of TAA in children.

In this study 210 patients from five different

centers-with the diagnosis PAR for at least I year; positive skin tests to dust, mites, mold, or animals;

and unsatisfactory response to antihistamines,

de-congestants, or immunotherapy-were enrolled.

Methods

The children (aged 4 through 12 years, mean age 9

years) were randomly assigned to one of three

treat-ment groups: placebo, TAA 82.5 pg/d, or TAA 165

pg/d. Medication was given three times a day for 12

weeks in a double-blind fashion. Response to

medi-cation was evaluated using symptom scores,

physi-cian evaluation, and in 44 patients, nasal airflow

measurements by anterior rhinomanometry. A

corn-plete blood cell count, chemistry panel, and morning

cortisol level were obtained before and after the study period.

Findings

The higher dose of TAA (165 pg/d) significantly improved rhinitis symptoms relative to placebo. The total nasal symptoms score and scores for stuffiness, itch, and sneezing were significantly better. Duration of rhinitis symptoms was reduced and nasal airflow, in a subset of patients, showed significant improve-ment. The lower dose of TAA (82.5 pg/d) was

supe-rior to placebo for the same parameters, but this im-provement was not as consistently significant as with the higher dose. There were no clinically significant adverse events; nasal irritation and epistaxis were rare, with a similar incidence in the treatment and

placebo groups. No changes in morning cortisol 1ev-els were noted.

Conclusions

TAA, 165 pg/d, was effective in controlling the

symptoms of PAR and improving nasal airflow in

pediatric patients. The lower dose, 82.5 pg/d, was less effective. Both doses were safe and well tolerated in the children studied.

This was a large study population and the first

investigation utilizing anterior rhinometry with

symptom scoring to demonstrate the efficacy of

in-tranasal steroid treatment for PAR in children. Intra-nasal steroids certainly present a safe, short-term al-ternative to using sedating antihistamines or central

nervous system stimulating decongestants in

chil-dren. Further studies are necessary to establish the safety of longer term (greater than 12 weeks) use of intranasal steroid, especially since the commercially

available TAA has 110 pg per spray.

Bim MILLER, MD Daly City, CA

PATHOPHYSIOLOGY

IMPACT OF CHILDHOOD ASTHMA ON HEALTH

Taylor WR, Newacheck PW. Pediatrics. 199290:657-662

(1) Determine the prevalence of childhood asthma; (2) describe the sociodemographic characteristics of children with asthma; and (3) describe asthma’s ef-fect on functional status and medical care utilization.

Method

In 1988, a questionnaire was administered in the

home to a randomly selected sample of 17 110

chil-dren younger than 18 years of age. The parent or

responsible adult family member was asked whether

the child had any asthma in the past 12 months. If

yes, other questions regarding limitation of activity,

school absenteeism, days confined to bed, number of

doctor contacts, and number of days hospitalized

were asked. Standard demographic data were also

obtained, including details about smokers in the

household.

Findings

The prevalence of asthma in this survey was 4.3%

(ie, the percentage of children who reported an

oc-currence of asthma in the past 12 months). Almost

30% of children with asthma had some limitation in

activity, compared with only 5% of children without

asthma. Ten percent of children with asthma had

severe disease as measured by frequency of bother

and limitations in function; these children accounted for 35% of hospitalizations for asthma and 77% of the

days in the hospital. The prevalence rate of asthma

among boys was 50% greater than among girls; the

rate in black children was 26% higher than among

white children. Children who were living in a

house-hold that earned less than the poverty level had a

significantly higher prevalence of asthma than

chil-dren in higher income households. Among

house-holds with a child with asthma, 41 % of households

had at least one member who smoked, which turned

out to be the same as the proportion among

house-holds with no child with asthma. The prevalence rate in children living in the “central metropolitan” area was significantly higher than other areas.

Almost 30% of children with asthma had some

limitation in activity, compared with only 5% of

chil-dren without asthma. Ten percent of children with

asthma had severe disease as measured by frequency of bother and limitations in function; these children accounted for 35% of hospitalizations for asthma and 77% of days in the hospital. Children were classified

as having severe asthma in 10% and moderate in

32%, with mild being 59%. Although black children

had more severe asthma than white children, the

number of doctor contacts with white children was

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limita-1993;92;314

Pediatrics