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AN INQUIRY INTO THE ETIOLOGY OF ACUTE BRONCHIOLITIS OF INFANTS SARAH H. WOOD, G. JOHN BUDDINGH and BENJAMIN F. ABBERGER, JR.

Pediatrics 1954;13;363

The online version of this article, along with updated information and services, is located on the World Wide Web at:
http://pediatrics.aappublications.org/content/13/4/363

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1954 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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AN

INQUIRY

INTO

TITlE

ETIOLOGY
OF
JohN

OF

ACUTE

BRONCHIOLITIS
By
SARAH

INFANTS
BUDDINCH,

H. WooD,
BENJAMIN

M.D.,#{176} G.

M.D.,

AND

F.
New

ABBEJICER,

Jn.,

M.D.f

Orleans of
Theagents from

CUTE

bronchiolitis diseases

is of it arouses

one early is

of

the infancy. evident

impor-

the the disease

opinion may same have has mechanical during presented


occurrence

that the serious early for


in

different capacity process, consequences factors infancy. further itself


infants

infectious for stimulatand involved study of Hospital investigaetiologic It careful has bacadmitted

taut

serious
several have havior of its manifestations
iii

concern clinical
been

ing the

pathologic

that bein of its

and
which

etiologic in and
are

studies recent certain years.


its

which

published
young
infants

characterize

of The cause berespiration The this


frequent

aspects
in

opportunity disease

epidemiology

described

the

because

reports Pratt, ward, Henderson


Shwachman

by 1944/ 1948,

Hubble Nelson Thompson and


et al.,

and and
and

Osborne, 1941,1 Smith,


Spector,

1945, Ben1949,

to of

the pediatric Louisiana at certain was

wards of Charity New Orleans. An phases of undertaken. with to bacterial regularity. to


to

Rosenzweig,
1951.

1951,

and

tion into by problem

the

therefore concerned

A
been to be
tion

specific
encountered responsibie
in the

causative
No single which for the Adams
autopsj

agent
bacterial

has

not
species

been been
teriologic has

largely

discovered.

I)ronchioles.

whether can be considered be inflammatory reac- would approach Goodpasture et al.,M al.1#{176} each
in

studies designed a particular encountered was deemed


excursion

determine species This as


experi-

with

be
provide

essential which
viral or

Adams
studies

and
on

et
series

reported
which

prelimmary

ence they
quent of

and
studies

information
into a

upon
possible

subsecom-

described epithelium.

inclusions The presence

in
and

the

bronchiolar
identity

bined

viral

and

bacterial

etiology

could

be

based. The results which have been ohthe suspected viral agent in these cases tamed from a study of 51 patients appear to could not be confirmed by inoculation of elucidate certain aspects of the pathogenesis laboratory animals. Hubble and Osborne of bronchiolitis in infants. Their presnoted that acute bronchiolitis of infants oc- acute entation in this report in no way implies crirred in England only during influenza that the etiology of the disease has been c1):deIll ics. Greengard and his ul
111

study

of

200

infants

under

one isolating
sputum

year a

of
and

adequately
PLAN

demonstrated.
OF STUDY AND METHODS

age
from

were body

unsuccessful
washings,

in Nelson

virus were
Selection series were of Patients:

nasopharyngeal

other
From

fluids.

and

Smith1

The
from

51

patients
new

in

the
to

selected

admissions

the pediatric wards of Charity Hospital of the 1)epartunents of Microbiology and Pediatrics, Louisiana State University School ofLouisiana at New Orleans over a period of 13 \Ieclicine and Charity Hospital, New Orleans. mo. extending from November 1951 to DecemAided I)y grants from the Eli Lilly Company. ber 1952. All were under 2 yr. of age. The folPresented in part before the Society for Pediatric lowing criteria for admission to the study were Research, Atlantic City, May 5, 1953. observed. The present illness consisted of a ( Received for publication Nov. 6, 1953.) cold of 2 to 12 (lays duration with abrupt the 0 Present ad(lreSS : Department of Pediatrics, development of a sudden turn for the worse Tulane University School of Medicine, New Orwith dyspnea asthe predominant feature. in leans. instances the time of onset of this acute Present address: 1225 North Orange Botule- most y(1, Orlando, Fla. illness was noted bythe mother. Moderate

363

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364
fever fants. had and cal varying pitched throughout frequently vealed Ilormalities. strated no was Several fever. tachycardia findings.

S.

H.

WOOD,
in most more the all of lungs. On but atelectasis cyanosis. were Liver

C.J. BUDDINCH
but not all ill the

AND
penicillin in-

B.
and

F.

ABBERGER,
sulfisoxazole any Methods antibacterial : the swabbings media: and

JR.
another therapy. upon aspirates inocutracheal were

present of Dyspnea, were Nearly degrees wheezes both palpable.

the

seriously most the

pulmonary patients Rales usually and if and admission few chest

without babies covered Bacteriologic emphysema physi- receipt and spleen showed and lated high on at the the nasopharyngeal

Immediately

constant

laboratory, following

discernible

1.

Bordet-Gengou

agar

plates

freshly
base with 1931) from agar and

pre15

emphysema Subsequent patchy

from Difco dehydrated werepared defibrinated rabbit blood; the RG reagar plates any other ab- 2. Levinthals fresh every day; films demon- prepared bronchopneu3. Blood agar brain-heart rabbit blood. plates

(Pittman,

prepared infusion

Difco 5%

monia
days

of varying
the ieucocyte

extent.
count

During
was

the
within

1st

2 or dehydrated 3
normal defibrinated

limits,
cytosis.

changing
of As before secretion soon

thereafter
Materials as antibiotic was collected practicable

to a relative
for after therapy collected by was

lympho-

The
successive various follows: of

cultures
plates days

were
were and

incubated
examined selected types were : on the Bile

aerobically
on colonies each from identified solubility coionies on of

at
4 the

37#{176}C.The Bacteriologic admission means

Collection Study: and tracheal

distinguishable

begun, as

DeLee
nasopharynx

aspirator.
was

Material
by

from
the

the

posterior tests nasal route plate

a Alpha-hemolytic were run

colonies directly

the

with

the

aid

of

a dissecting

microscope.

with swabs by Kendrick, were containing man3) delay. and On

prepared Lawson about brought several 0.5

in the manner and Miller.12 transferred cc. to Levinthals the laboratory these to

immediately

from such colonies were identified described Organisms pneumococci as to type by the Quellung The swabs as with 1-34 typing sera. If typing could small tubesreaction broth

occasions

be accomplished (Pitt-not in blood broth without tures toneally into mice. procedures admin- cific
to relieve toneal cyanosis. colonies type could exudate. which be Bile failed

in
were In

this

manner,
instances with

subculintraperithe the spepenre-

inoculated

most

were
istered the

postponed
for patients a

until
sufficiently severe

oxygen
long dyspnea

had

been
time and

determined soluble to kill

alpha-hemolytic mice were

Blood
days mately specimen tients allowed serum tor
by

for
after

serum
admission after 4 wk.

was
onset after

obtained
and of from onset. the again

within
at of disease. many The

2 vk. was 3 to

as nonpathogenic pneumococci. or garded 3 All bile insoluble alpha-hemolytic approxiof gram-positive cocci A third consisting

were

colonies desig-

obtained

the

blood and refrigeradirected

to clot removed : The pediatric measures

at room temperature before storage in the plan of therapy the of was

nated as alpha-hemolytic streptococci. pahemolytic streptococci were was Beta as by colony characteristics, the the such

identified
surround-

ing
stained

zone to

of
smears.

clear
They

hemolysis
were at

and
transferred

by
to

gramblood or

at 5#{176}C. Therapy services of consisted


tent.

broth
efforts Imtyping. the

confirm
were made

their

hemolytic
serologic

capacity. No
grouping andtains transferred slants and

the mediate

hospital. relieving

anoxia
ity in

by
an

supplying
oxygen

oxygen with The original

added plan

humidwas to ing
in 7

Neisseria

in

identified gram-stained agar the and

by morphology smears were chocolate agar

to to

use either dosages of

chloramphenicol 60 to 100

or terramycin mg./kg./day for

plain

in

alternate

cases.

Prejudice
developed so that terramycin. severely ill virulent Digoxin failure the

against
during majority Penicillin patients

the
of

dextrose, days Only use


the countered.

maltose,
nonpathogenic

sucrose

and
varieties

lactose
were by colony

agar.
encharreaction

of chloramphenicol course of the study patients added for received a few

hemolytic Str. or mouse were isolated by culture. tered when cardiac

after Diphtheroids pneumococci acteristics was adminisdiscerned

were the Staphylococci acteristics, morphology was by Grams method. beta were and were

identified and identified

staining
colony by

charstaining ann by

morphology identified by

and

was

Grams or only Coliforms

method.
morphology

suspected.

One

of

the

patients

received

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ETIOLOGY
staining Kliglers mannite, The ferred
made

OF
transferred

ACUTE
to

BRONCHIOLITIS
regarded it not been as being for the of particular that micro-organin

365
interest the ma-

by Grams iron lactose various to to as identify agar and organisms coliforms

method
and xylose of and them. Colonies

and

been

to this no were
OD

dextrose, fermentation group further identified

maltose, had tubes. jority were effort represent was

fact

of
In

tlie
as

first
the

cultures
predominating

H. it

influenzae was present

was in and

ism.

several
pure

instances
culture.

Hemophilus: their and to tunes


as

by agar agar

almost

typical satellite

appearance colonies plates. agar. tv1)ed by

Levinthals on blood were 12 to

The tures in

beta which

hemolytic occurred H. influenzae This most represented


of the of infectious penicillin

streptococci in was many presentin

and typabie hr.,

pneumococci numbers. in the

ciiiwas infants
The

Bordet-Gengou Levinthals were

These Young, the Quellung


1
TEIIIA
AND

transferred 24

significant culencountered and presumably


complication

reaction

with

combination severely ill an


process. produced in these

additional

IABLE
I N(I )EN( FIUST
:
OF

I )usF:ut:NT
(ULTUuIES
OF A(ITR

B;u

ISOLATRI)

FtOM

administration marked clinical

1uet( uIE.tL
GEAL

AsuIuATuc

N%soruutunx(tsEs

FROM .5!
BusoNuI
IOLITIS

improvement

cases cultures.

with
and
lreseuut iuu

the

disappearance
from

of
subsequent

the

Streptococci strepand after therapy

pneumococci

The

staphylococci, coliforms ill the well of

aipha-hemolytic usually cultures established. H. influenzae


in

Bacterial

((i(S

No.

of

(fuses taphy1oeocei 49
type type a 1) tvpahle uiouitypshIc streptococci streptococci

tococci and predominated therapy The was response

persisted obtained to

H.
II.

infiueuizae
iuiflueiizae puieuuuuouuiae puietinioniac heuuuolytic heunolytic

26 6
S

I).

1).
alpha 1)eta

1)5

-::
IS

as indicated tures varied most instances, ism was noted to


isms

by its occurrence greatly from disappearance over a period In


be

repeat ciiicase to case. In of the organof 3 to 4 days these


in of

Coliforms

a week.
could

some
recovered longer

cases
periods

micro-organgreatly time. reduced By the

type in

specific

H. infiuenzae
Those type types require or in ally of which were the with with a, as H.
case

antiserum could d, e not prepared and antiserum

prepared be f, for was but

numbers

for

chickens. as of to to

which b, the H. c, x and

identi- time against enzae were while growth and not

the could
cohiform to

patients usually
colonies be

had no

recovered, longer
persisted that the

H. be
in

influ-

fled each found were

cultured
varying cultural

staphylococcus,

alpha-streptococcus

v factors

considered

influenzae
of the

(nonspecific).

H. pertussis
countered Results frequency species patilogenic

parapertussis series. Studies: different be considered

numbers. en- It is

emphasized

Bacteriologic which might

Tile bacterial to

methods were vide satisfactory lation ble be of the experience

deliberately requirements Hemophilus in their in cultures


facts have interested

designed for groups.

to the and

proisotheir to be

Considcrafound
in

recognition was
been

isolated the these in


of tile

from 51

the cases

first is

ciii- maintenance
essential. sumby every These

tures obtained from marized in table 1. In most respects


110

recognized these

investigator

results much to the

provided significance possible


listed.

fastidious with
pendent

micro-organisms. which
i1Oll

The isolated
to

frequency is directly
H. Influenzae Acute Brozi-

evidence be
role

to attached

which

they these

are

de-

could
etiologic

respect
bacteria

factors.
Patients with

general other
appeared

they conformed investigators. The


in

to the findings of striking exception


of

In Antibody Types a and

Response b in

chliOlitis

: H.

The influenzae from

apparent types majority the

consistency a and of the b were

with repatients

the

high

incidence

enzae

types

or

b.

This

would

H. influ- which covered not have

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

366
led spoise isms. to tube ences lowing proved when Antigen
enzae type

S. to an of Much adapting in

H.

WOOD, of to the

G.J. BUDDINGH antibody micro-organwas devoted and differThe which re#42

AND
and checked

B.

F.

ABBERGER,
water for the antigen before use

JR.
ZC() the pOillt.

investigation the the specific patients unsuccessful Quellung to antibody agglutination

distilled

these effort reaction

The
was serial lung against folspecific

specificity
daily reactioll previously antiseruni

of and

suspensions by the Quelagglutination dilutions in of chickens.

by

slide

agglutination slide to be carefully


aand

demonstrate content. technic,

standardized prepared

These for and


bsamples

suspensions use for when a few


collected

remamed stored days


of the froni

satisfactory 4 to
The individual

reproducible
performed, Smooth H. influenzac

and
was H.

reliable
developed. influtype

at

5#{176}C. for
-

5 days
serum pa-

longer
Test: each

at 20#{176}C.

Suspensions:

Performance

colonies capsulated
heavily Levinthals incubation off days for coarse
centrifuged

which by
inoculated agar at chilled
was

were the

shown Quellung
onto

to
freshly After

be

well

reaction
six was saline. at 5#{176}C. for temperature

entient were were suspension comparative


dilutions of and

tested against in a smgle test results.


inultiples

tile samentigen a run to provide were


10, beginning controls

prepared hours washed two

They
of serum

set
with

inup

plates. 37#{176}C.,the 0.5% then at The stored at 1000

growth

the

undiluted in
of

sample
negative

through A small
was pipette

1-120. Known
were

into and 10

formalized this rpm to

Thepositive

suspension

included
respective by means a

each
serum

test.

drop
to

of
transferred each

each
half

centrifuged

dilution

minutes particles.
at

remove
was

all at 2500

a capillary

supernatant

again of

cl#{128}anlide. s

5#{176}C. for

20

minutes fluid was in


to a a

The

antigen
of H.

suspensions
the influenzae

were
test type run.

kept
A a was

chilled
capiltranswas roan-

rpm.
and which a

The the

supernatant sediment
saline adjusted to of 250 a in

discarded cold
which

resuspended
standard

in an ice 0.5%lary drop ferred H. to A


gavethe

bath during drop other amount

formalized conformed reading

turbidity

to one the

of the type drop of

serum
suspension b tile in

dilutionand
same

influcnzae small

Klctt-Summerscn

photoelectric

colorimeter

using

a blue

added filterncr.

Loefflers

alkaline

Antbody

to H. to
H.

nfl.
nfl.

type
type

a
b

90 2

Antibody

70-80

II-

50

60

>.

a
0

30-40

3 3

z
4

10-20

u
2 3

I
4

I
5 NUMBER

6 OF

1 7 CASES

1 8

u
0 9
II

13

CHART

1. I)istnibution

of antibody

response

to H.

influenzae

in 46

patients

with

actute

bronchiohitis.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

ETIOLOGY
24

OF

ACUTE

BRONCHIOLITIS

367

U
20
U,

Titer
Titer

rise
rise

+
only

nfl.

D U

Titer
16 High

rise
titer

B
in

rough
l5t spec.

H. + H.

nfl. nfl

w
U,
1 L)

D
U-

H.

infl.

only

2
cr
LU

II

Negative

: z

8 5 4 22

TYPE

TYPE of

CulAuir

2.

Isolation

I I.

infloenzae,

110(1 , b

51 Illetilylene of oughl tilting


against

cases each
means by

of

acute with thor-body


fll1l by

and specific bronchiohitis. acute titer oI)tained. individual of

serologic

rcspone

iii

blue inoculating mixed. the slide

was The
Witil

added loop Pools a gentle


in

to and were

i)ronchiolitis 1 to Tile revealed was and duration 90 ill the

revealed first second a

an

anti-

ai

tile

pools agitated motion


in-

serum specimen decrease

specifrom in between disease was evident (innand titer

rotary
a strong

this

a \llit(.

background

to
the

1 to
No severity

40.
correlation #{128}Iiscernible of titer. levels
not

direct
fine cluml)s taming llall(1
tioii.

light. but

\Vitilin definite

:30 seconds
rnethylene visil)le
ill

to

2 Illinutes
blue-stained cona reacthe that
ing

the It

l)ecame specific hells Doubtful Quellung sarnl)le was to titer


ill

tile of were

serum Occasionally the checked

eventual the possible from increase interval had a had and


no

antibody high antibody


were

antibody. \isualizatioll reactions test. The whicil

attained
maintained.

aided

convalescence

It
of

with was

to

obtain
14 of in detectable

a third specimen
the antibody the antibodies decrease at10 in titer. patients who titers. onset, and

the serum tion pacity The

highest
produced tested

dilution
for its

of
agglutina-

a 5erilIll
eloped ca- S these showed r- remaining, onset, The logic week

dcAt 5 :3 The 6 the of

each give tile assigned

instance a positive highest results


in antibody

following

Quellung toach e serum


dilution and these
in

reaction. sample
which capsular determina-

marked tested iio

indicated duced swelling. tioiis An enzae could No are


increase

to

13
antibody. from

weeks
the \vitll

after
1)acterioH. influ-

both Tile

gross graphically

agglutination from presented titer course


in

demonstrable results studies

colilbined serologic

chart
to H. the acute
happens

1.
infodisease

enzae sented Including

types
Ill

aand
2.

1) are four froni

graphically whoii rough


combined

preon-

a or h during

the 1)resellt One


\ilO in

of of in the tile
\Vil()

chart

ie
antii)ody

denlonstrated was of 44.

46

patients.

the
strains

serum tpable

were aild
H. influenzae
All ill

isolated,
was increase
13

S1WCiI11CI1

patiellt,

I)acteniologic
fection with and

serologic

evidence
obtained ill Tile from titer

for
in

in-

to i)e
had
siloweci

the only
a 1 to
a

one
40 titer
sui)sequent

received the

no specitilen
to

therapy.

acute
increase

:3:3 of
was organism a
Wi1OITI

the I)cltiellts.
demonstrated was no increase

only microthree ill

1 to

80.
with

others.

Another three week

cilild

who history

was of

admitted illness

recovered intiter

compatible

could

be

demon-

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

368 strated. and ill H. antibodies

S. H.

WOOD,
was not

G. J.

BUDDINGH
not recovered

AND
branes saline hour of strain.

B. F.

ABBERGER,
with

JR.
0. 1 cc. of a from 18 to 24 of further
virus-infected

influenzae could two

be

demonstrated

were inoculated suspension prepared Levinthai Upon at 35 12 to agar to 18 hours

the The
cases

remaining antibody
proved

of
be

the in
type

series. the type majority


In specific.

cultures

the

rough incubawere fluid pipette. grew

response
to

tile

tion five

37#{176}C. the ill

individuals covered, could


ill

from cross be 1 to failure 10 demonstrated dilution to


may measures

whom agglutination in of

a with

was type

reembryos, inoculated b aspirated or In most from out imcally and in

fresh Levinthals with a drop by


instances

agar plates of allantoic

the the

undiluted serum.

the The

means the 18 hours

of a capillary colonies which were Type reactions Rough into H. normal H. were of from
an

isolate who perhaps

H. developed

influcnzae a good be attributed before administra-

12 to iridescent. agglutination

smooth specific could

and

typireadily

the miiiie
to

individuals response
therapeutic

Quellung infuenzae controlem-

instituted

hospitalization. tion could viduals sponse The of be


ill

A history sulfonamides established whom was a in specific

of and/or 5

the of

be demonstrated. strains inoculated


bryos underwent

antibiotics the antibody type the 13

no

change.

mdi- Two re- lated this

strains from procedure.


a. The

of the patient

rough One

influenzae available reverted this


in

isofor to strain
anti-

patients

only recovery

demonstrated. of H. influenzae

them whom
increase

a from type was body


reverted

24 patients in antibodies tion


only

who also developed to this type and specific


others is

an increase demonstratiter increase regarded

isolated titer
to

developed to type
type b

a only. and
an

The
increase

other
in anti-

strain

of
in

type
11

antibody
of particular

interest. body

H.

influenzae

type slight, if only a few


been

is

generally

in

the

titer to patient.

type

b only Investigations arc


confirmed

was being

demonstrated into this incontinued


that it can be

as having ertics. In
genicity

any, pathog#{128}nic instances has its


by its

phenomenon prop- triguing have thus far patho- and


recovery

established

from exander

cases

of

H. 1942,

influenzae and

meningitis Alexander, of

readily reproduced H. influenzae recovered (AlDetermination of of were the

with

strains from other Cold Patients:

of rough sources. Thirty-six

et al.,

1943s).

Hemagglutidetermine to

Reversion Strain of
Embryos

to Type H. Influcnzae
Infected

Specificity Cultured Influenza whether

The

problem attached untypable

as

with to

Response Rough nm of scra in Chick pairs whether cold Virus: during serum against 0 could by
detected.

the

tested of run
In none

aggiutinins the

had

developed

significance recovery influcnzac types


inoculation

could be of rough was


to cultural

to the occasional strains of H. during this to


and

the course samples were the an same


ill

illness. All the at the same time of patients titer be human of the

0.5% cold

suspension agglutmnmn

encountered induce to experiments reversion by virus. effect The embryos 1 strain hours old 24 It the reversion
methods

study.

Efforts type

erythrocytes. increase

specific
mouse

proved literature the which achieved chimpanzees cold same


embryos. day

be on

unsuccessful. this to infected appeared could be chorioallantois of later subject of Dochcz type intranasal with

A review called et of rough the


in

of 1932,16

attention al., strains inoculation

the Determination tion Response to

of

to serum tested

the AntihemagglutinaInfluenza Virus samples for an against


influenza

A,

B 46

and paA

C: in

The paired

from increase
influenza B Lee)

tients were was hemagglutination of

antiin and

titer C (J.J.). The

probable produced of 10

common prime influenza that the chick or with Eighteen with glutination 11 theincrease

( Cuppett),
cholera filtrate

sera to

were

not or
in

treated
ag-

destroy normal

F.M. to

was inoculated influenza virus. the virus-infected

inhibitors. A fourfold in titer against the influenza could paired not scra be demonstrated Five tested.

greater A or
any

strains

mem- of

the

patients

of

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

ETIOLOGY
tile fourfold,
influenza

OF developed

ACUTE

BRONCHIOLITIS
\Vilson, recovered studied Dulln aild

369
Blair,

series

were i)ut
IlOt

found

to

have

ainvestigators.
1924,20 of They patients

C (luring

greater, increase the course of the


DIscussIoN

against disease.

H. 1920
to

influenzae
during the

from
influenza

100%
epi-

demics
These inquiry olitis of investigations into constitute a partial

of
were

1919,
able

and during

1924 the
in

in

Ulster.

demonstrate

agglutinins

in
of the tive of has

the

serum from
results

obtained all
were

pyrexial Nega208 of 220

the
and

etiology
infancy. serologic of the

of
The

acute
results studies

bronchigive role

period
rise controls.

of work

these
obtained

individuals. Alexander,
that antibodies

early

bacteriologic to a consideration

The
clearly

of

1943,
de-

possible

indicated

H.
genesis dence

influenzae
of indicates this

types
disease.

a and infection
an

b
Much

in with

the
of the

patho- velop
cvi- It

in appears

H. for

influenzae to be of some infection


obtained by

type with 24 and of by the

b H.

meningitis. that influenzae


and

significance
bacteriologic

that
constituted

these

evidence
type a was

micro-organisms

important

part
dence etiologic

of

the
agent

process.
would

More H. to
Attempts have

conclusive infiucnzae
been to of inoculation

for implicating

as the
accomthe

cviserologic the actions

means only in been


The

in 11

serologic 51 by patients. others


indicate

reas

others encountered
present

available

had
ease plish organism

it

been
tilis with by

possible
pure intra-amniotic

reproduce

It has rarely dis- pathogen. a that H. having acute The


far comparable

studies

experimentally.

influenzae pathogenic bronchiolitis problem not be clinical of control

type

a must properties of

be

considered in respect

cultures

micro- as of

to

infants. an for adequate this solved. is encountered study This

10
been

to

12

day

chick
into

embryos
suckling mice

or

by
have

intranasal
thus

obtaining series syndrome

instillation

unsuccessful.

could Cecil,
1920,17

satisfactorily

Blake produce the H.


mucosa. autopsy pneumonia

and

were

able

to

particular

bronchiolitis of pure to the


bacillus

in

application influenzae
Pfeiffers from

monkeys following mostly in early infancy. Comparable situacultures of virulent tions in this age group in which bronchial nasal and bronchial or bronchiolar inflammatory reactions dewas recovered at velop

rarely who had

presented ingested

themselves. and control. of a


infants

One kerosene

in-

95% with results

of

40 from

cases

of by

bronchoListon,

fant

inhaled

bronchiolitis bacteriologic of
H.
of 06 1

1929.
ies on

Tile
a series

provided a negative stud- and serologic survey


number of normal

A bacteriologic sufficiently large


in the age group

cases between
regard

bronchiolitis 1927 and


influenzae

Ill

infants

occurring 1941,19 to

1933

was
ascilities.

beyond

the of the of H.
at drawing Yang,

capacity available influcnzae the

of

available on
chil-

fathe

led
tile

Trask, etiologic that


an

agent. this
factor

These micro-organism
in

observations may
the

dicate
1)e bronchial

often

in- A survey incidence


of dren attempts

literature
in

normal

important

production

emphasizes
comparison.

difficulty
significant 1941,21

inherent
isolated

in

The
a and
ess

and bronchiolar conclusion that


b were involved strongly An increase obtained in

inflammation. H. influcnzac
the in in infectious by the specific the present

conclusions H.

types by

proc- influenzae scro- 8 years inHe tween

from
during

26% of 40
a five month

children
winter

from children evidence H.


Ill-

2 to
period.

is also

supported

logic vestigation. agamst covered


ill

evidence

antibody

also found that 4% of 200 1 and 8 years of age without infection from of 15 isolated harboured
1943,15 recovered

be-

the
by of H. the detected

type
culture cases. in been

of
could An 13

micro-organism
be increase others. in That antibody noted

retiter

of

the of

micro-organism. over 55% were patients. a

demonstrated

33

Alexander, onlyfluenzac period


protype

5% months. from

typable 847 children Of these, gravely ill

was with duction

infection by

infuenzae has

stimulates previously

I)

other Strahers

survey22

of

the

nasopharyngeal

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

.370 flora, i)Oys revealed SIllOoth casion ey,2 over ranging

S.
a

H.
4

WOOD,
year period,

C.J. BUDDINGH
of 200 school infants

AND
is

B.
well

F.

ABBERGER,
justified and

JR.
has not l)een

from 4 that

to

14
on

years carrier
ay

of

the

maximum
obtained

age, refuted rate of gations


occircumstances

by
into

these
the into

studies.
problem account

Further
wllich are in take

investitlleSe progress.

strains

single

did
she

not
found

exceed
8% of

19%.
50

In

another
from

sur- Chick
2 may to

embryos
provide

infected
suitable

with
conditions may

H.
in

influenzae
\Vilicll

children

11

years

influenzae. isolated normal influenzae

of age to be On the other


H. children. influenzae

carriers hand,
from

of smooth Rabe, 1948,2


32.8% of

H. the gated
1356 bacteria

responsible and other with


is also

viral agent detected. than agents


excluded. not

be
may

propathat
corn-

The H. influenzae to

probability produce the

A comparison
in the

of reported
but significance.

the
present

high carrier
permits The

incidence
series with

bine of H. ease
that

viral

dis-

most
haps as to

of

the
its

suggestive

in It is nevertheless apparent that during is per-the year in which this study was undertaken no conclusions in this area, evidence for infection with demonstrated influenzae types a and b was obtained in a

surveys

H.

antibody further in
many

response implicating pathogenesis


ways analogous

may be H. influenzac of the the to


and 1941,25 by

the

considered as highly significant as a factor with acute disease. It is micro-organism in observations agent by
Thompamong

proportion

of

51

infants

bronchiolitis. constitutes be decided


on

Whether the the sole basis studies of

this etiologic the of this

cannot

made Trask
SOIl

with et and
to

pneumococcal Edwards,

infections
Terry, who,

available disease for the influenzae


be ing

evidence.

Future

al., 1930,24 showed


these

others,
response

that denote of an

the their

specific
agents

serologic
could

will have to make proper isolation and identification as to specific type, and specific
SUMMARY

provisions of H. for follow-

infectious

the

immune
AND

response.
CONCLUSIONS

considered the disease The absence

to

participation in the

in cold Tracheal obtained


of age with

process. increase titer or the influenza does these of not diseases a fourfold titer against antihemagglutinating A and B strongly that were the not increase influenza involved. in swabs sug-years subjected The anti-during

aspirates from
acute

and 51 infants

nasopharyngeal
under were 2 bronchiolitis

agglutinin titer against gests agents The but of detection

prove

causative

to cases the

careful

bacteriologic

study.

in this 13 month

series were encountered period from November 1, 1952. recovered from to be 36 be H. of H. in-

hemagglutination in five critical rence


immune

cases is of some interest. Much work must be done on the occur- the 51 infants. of influenza virus infection and the influenzae type
response

C 1, 1951, to December H. influenzae was more

Of these, 26 proved a and 6 proved to b. in The strains. type specific four remaining

before can The been of chick


tiohl

the be

results

it of

provokes these tests

in in

infants fluenzae this study rough An havemeasured strains and


onstrated

type untypable increase the

were antibody technic be demin anti-

correctly limited made on the influenzac embryos problem The


as

evaluated. observations reversal in may influenza be pertinent of which rough virus-infected to a

by

by a slide Quellung
in 46 infants.

agglutination reaction could


No increase to H.

H.

of the bronchiolitis.
micro-organism

of the etiology important role


a secondary

solu-body titer could be of acute increase 111 antibody of this pe a was ty demonstrated flucnzae
that

demonstrated
titer .37 and in

inAn 5.
influenzae

to

H.

in-

component

type

b in

9 of

the H.

series. and serologic influenzae type process


in anti-

in epidemic
is virus well

influenza
recognized.

and
The

in swine
contention

influenza partici-

Combined evidence a a was inobtained

bacteriologic indicating that 26

or
iii

viruses the

as

yet

unrecognized of bronchiolitis

pate

pathogenesis

involved in

in the infectious cases. An increase

was

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

ETIOLOGY
l)O(ly ill titer
Otilers.

OF
demonstrated

ACUTE Hospital nonD. Mrs. in ful


Smith

BRONCHIOLITIS is Guidry, Joan technical


gave

:371

to
Ill

type

only

was

gratefully Mrs. Mary Herbert assistance.


mucil

acknowledged. R. Dr.
appreciated

Mr. and H. D. tile help-

11

two
were was

from

whom

rougil
an increase Evidence

J.

Wofford
much

tvpahle t:ter to

strains ty1)e a

isolated, demonstrated.

H.

provided

Margaret
encourage-

for
Ill

infection
:37 of the
type
III

with
51
a

type
infants.
was

a was
From
recovered

thus
2

obtained
infants

ment H.
study.

and

helpful

criticism

throughout

influeIlZae

but
be

no indemon-

crease
strated.

antibody bacteriologic for infection obtained was

titer

could and with H.

REFERENCES

Combined evidence type b

serologic influenzae An in-

1.

5 infants. in type
more

2. 3.

Hubble, D., bronchioiitis 107, 1941. Pratt, E. L.,

and
in

Osborne, children,

G. Bnit.

R., Acute NI.J. 1: in infaults,

Acute and

bronchiolitis

crease
l4

in
others.

titer
A in strains

to
titer 2

b
increase

was
to

demonstrated
type was b rough 4. 5. obwhom

M.
Nelson,

Clin.
W.,

North

America
Smith, L.

28: 1098,
W.,

1944.

Generalized

demonstrated untypable

from

obstructive
Pediat. Benward, children, Thompson, mycin infants, 26:36,

emphysema
1945.

in

infants,

J.
in

were isolated.

Evidence obtained type b


was

for
111

infection 9 of the
in H.

with 51 infallts.

type H.
of

b was thus influenzae


increase isolated

J. J. J.

H., Acute bronchiolitis Lancet 68:24, 1948.


and Spector, AureoS., of acute bronchiolitis

without tamed No an

evidence one. influenzae in

titer were

B. F., in therapy

of

6.
nor

Henderson,
Bronchiolitis

Pediat. 35:546, A. T., and


in

1949. Rosenzweig,
U. S. Army

S.,

could demonof were the nega7.

infancy,

increase
Ill

antibody remaining

titer 2 reactions

be infants

strated
series.

the

Cold tivc in
virus sera. ill virus series. in A A C

hemagglutinin
36 pairs or B

Armed Forces NI. J. 2:943, 1951. Shwachman, H., Foley, C. E., and Cook, C. D., Aureomycin in pediatrcs: Review, 1. Pediat. 38:91, 1951.
Goodpasture, Swanson, E. W., H. S., and Auerbach, Cotter, E. S. H., F., Virus

8.

of
could

scra
be but

tested. titer
detected not titer

No to
greater, to in

increase
46 paired increase 9.

antihemagglutinating
fourfold, was detected

influenza

pneumonia of demic infection,


997, Adams, 1939.

infants secondary Am. J. Dis. Child.

to
57:

epi-

antihemagglutmnation

influenza

5in patients untypable typable


the

of H.
micro-organ-

the 10. influstrains influa 12. partibronother 13. 11.

Reversion enzae
was isms

of smooth
by

rough specifically
culturing

to
achieved

J. M., Primary virus pneumonitis with cytoplasmic inclusion bodies J.A.M.A. 116:925, 1941. Adams, J. M., Green, R. C., Evans, C. A., and Beach, N., Primary virus pliellmonitis, J. Pediat. 20:405, 1942. Greengard, J., Baycroft, W. B., and Frank, L. S. Observations on pneumonia inin
,

in chick

embryos type be A.
that

infected
H. influenzae

with types as of acute

fants

at

Cook

County

Hospital-Season

enza
It
and

virus
is

postulated

1941, Kendrick,

b must in
of

strongly pathogenesis
infancy. early

considered
Whether

J. J.,
York, tion,
Pittman,

Illinois M. J. 80:391, P., Lawson, G. MeL., Hemophilus Pertussis:


and Reagents,

1941. and Miller, Diagnostic


ed. 3, New

Procedures

cipating
chiolitis

the

American Public Inc., p. 141.


M., Variation and

Health
type

Associaspecificity

bacterial tion cated i)e of in determined

or viral bacteria the by

agents and

alone viruses of this

or can

a combinabe implidiseasemust

etiology further

14.

illvestigation.

ACKNOWLEDGMENTs

The
bers Tulane of

enthusiastic
the Louisiana

cooperation
State

of Staffs of

the

mem- 15.
and

University

Pediatrics

House

Charity

16.

in bacterial species H. influenzae, J. Exper. Med. 53:471, 1931. Alexander, Hattie, Ellis, C., and Leedy, Treatment of type specific Hemophilus infiuenzae infections in infancy and childhood, J. Pediat. 20:673, 1942. Alexander, Hattie, Experimental basis therapy of H. influenzae infections, Am. J. Dis. Child. 66:160, 1943. Dochez, A. R., Mills, K. C., and Kneeland,

G.,

for

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372

S.

H.

WOOD,

C. J. BUDDINGH

AND

B.

F.

ABBERGER,

JR.

17.

IT., Jr. , Variation of H. influenzae during nasofar#{237}ngeo y de aspiraci#{243}n traqueal. Se aisl#{243} acute respiratory infection in chimpanH. influenzae Il 36 de los 51 lactoantes: 26 zee, Proc. Soc. Exper. Biol. & Med. 30:fueron del tipo a, 6 tip() 1) Y los cuatr() restantes 314, 1932. rugosas no tipificables. Blake, F. G., and Cecil, R. L., Studies on Por medio de la t#{233}cnica deglutinaci#{243}n a en experimental pneumonia. IX. Production l#{225}mina y Ia reacci#{243}n de Quellung se demostr#{243} in monkeys of acute respiratory diseare en los anticuerpos especlficos tipo resembling influenza by inoculation with un aumento en 46 ni#{241}os, en 5 no se observ#{243}; para y el tipo B. influenzae, J. Exper. Med. 32:691,

18.

19.

20.

a ci aumento fu#{233} 37 y para en el tipo en 9 h 1920. Liston, W. G., Note on bacteriology deof Ia senie. Se encontraron en 26 casos pruebas bronchopneumonia in children, Arch. bacteriol#{243}gicas y serol#{243}gicas de que el agente Dis. Childhood 4:283, 1929. causal era el H. inflvenzae tipo a;el aumento Trask, J. D., Pneumonias, in Brennemans de Ia titulaci#{243}n de anticuerpos tipo fue a enPractice of Pediatrics, Hagerstown, Md., contrado solo en otros once asI como dos en Williams & Wilkins Company, 1941, vol. con cepas rugosas no tipificables; asI tuvierQn se 2, chap. 48. datos de infecci#{243}n con el tipo a en 37 de los Wilson, W. J., Dunn, J. H., and Blair, E. El H. tipo a se aisl#{243}n dos e ni#{241}ossin M., Agglutinins for Pfeiffers bacillus ninos.

51

21. 22.

en ellos se observara elevaci#{243}n de los found in sera of patients suffering from que nIveles de anticuerpos. influenza and other diseases, J. Path. & Bact. 27:336, 1924. Se obtuvieron pruebas bacteniol#{243}gicas y seroYang, H. S., Nasal flora in children in day l#{243}gicas de infeci#{243}n con H. influenzae tipo 1) nursery, Am. J. Dis. Child. 61 :262, 1941. en cinco niflos, aumento en los anticuerpos al Straher, E. A., Serological typing of menin- tipo b en does m#{225}s, asI como en otros dos CO geal strains of H. influenzae, Lancet cepas rugosas no tipificables. En esta forma se

248:817,
E.
PEDIATRICS

1945.

23.

Rabe,

F.,

Infectious 2:255, 1948.

croup.
,

I.

Etiology, D.

tuvo

un

total

de

nueve

de

los

51

lactantes

con dos

infecci#{243}n tipo

b. Hubo
de

un
de Ia

caso
senielb

deH.
se

influenzae
En los aislaron H. en Ia titulareaclas

24.

Trask, M.,

J.
and

D.,

ODonovan, Beebe, A. A.,

C. Moore, Studies on
Mortality, antibodies J. Clin,

tipo pneu- casos


blood
influenzae

b sin

aumento

titulaci#{243}n.

restrantes

25.

inonia in children. I. cultures, and humoral pneumococcus pneumonia, vestigation 8:623, 1930. Terry, L. L., Thompson,
wards,

ni

se demostr#{243} aumento
de sueros en

In-

in ci#{243}n anticuerpos. de En 36 pares ciones de

estudiados frIo fueron

J.

C.,

Immune

P., response

J.

and

treated monia,

cases of pneumococcal Am. J. M. Sc. 201:574,


SPANISH ABSTRACT

Edtivas; en 46 sueros pareados no se cncontr#{243} in drug aumento de la titulaei#{243}n antihemoglutmnante a pneulos virus de Influenza A y B. Sin embargo, en 1941.
cinco cuatro aglutmnante pacientes veces al de mayor virus de la serie de Influenza se vi#{243} un C. en de las a cepas los
en

hemoaglutininas

nega-

aumento antihemoembniInfluenza

titulaci#{243}n

Encuesta Bronquiolitis
Siendo fermedades natural que

Sobre

la Aguda

EtiologIa de de la Infancia
aguda de se una de Ia hayan

la
en-

Sembrando ones de polio tipo A se influenzae no es especIficamente Por iiltimo, influenzae raz#{243}n casi
patog#{233}nesis

los microorganismos infectados con virus obtuvo inversion


y rugosas

Ia bronquiolitis m#{225}s importantes recientemente

las
infancia,

de

cepas

H. de
lisas

tipificables tipificables. los autores tipos cierta, de Ia para a

publicado

postulan que considerarse, participantes aguda requieren si en por se

H.
COIl

diversos estudios clmnicos, etiol#{243}gicos y epidemiol#{243}gicos; sin embargo, hasta la fecha no ha se descubierto El ciones menores aguda, gica doce de artIculo realizadas de sujetos cuidadosa meses, diciembre del de hicieron dos a lo. ci agente actual por aflos una de 1952. con de especIfico se los reflere autores edad con en Los cultivos un de estudios de causal. a las en observa51

y debell b como bronquiolitis determinar

Ia de Ia mayores Ia sI etiolosolos o

bronquiolitis perlodo 1951

infancia. ni#{241}os investigaciones gla de

Sin este

embargo, padecimiento o agentes de ambos.

investigaci#{243}n noviembre

bacteriol#{243}-

pueden virales,

impliearse

y observados

otras bacterias de en combinaci#{243}n al lo.

bacterioproducto

Louisiana School of

State Medicine

University

l#{243}gicos se

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on November 12, 2012

AN INQUIRY INTO THE ETIOLOGY OF ACUTE BRONCHIOLITIS OF INFANTS SARAH H. WOOD, G. JOHN BUDDINGH and BENJAMIN F. ABBERGER, JR. Pediatrics 1954;13;363
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1954 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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