NITROGEN DIOXIDE AND LOWER RESPIRATORY ILLNESS

(1)

(Received August 27, revision accepted for publication October 15, 1970.)

ADDRESS FOR REPRINTS: (J.F.F.) Ecological Research Branch, DHER, National Air Pollution Control

Administration, 411 W. Chapel Hill Street, Durham, North Carolina 27701.

PEDIATRICS, Vol.47, No. 2, February 1971

391

NITROGEN

DIOXIDE

AND

LOWER

RESPIRATORY

ILLNESS

Martin E. Pearlman, M.D., John F. Finklea, M.D., John P. Creason, M.S., Carl M. Shy, M.D.,

Marion M. Young, M.D., and Robert J. M. Horton, M.D.

From the Division of Health Effects Research; Bureau of Criteria and Standards, National Air Pollution Control Administration, Environmental Health Service, Department of Health,

Education and Welfare, Durham, North Carolina

ABSTRACT. Significantly increased bronchitis

morbidity was reported among elementary school

children exposed for 2 and 3 years and infant

co-horts exposed for 3 years to elevated levels of

ni-trogen dioxide in the ambient air. Both the relative proportion of children affected and the frequency

of attacks in these cases were higher in the

pol-luted areas. Morbidity associated with croup,

pneu-monia, and hospitalizations did not significantly

differ among the three exposure areas

studied-high, intermediate, and low. Retrospective

ques-tionnaire responses were validated by physician

and hospital records. Question sensitivity exceeded

67% and specificity 70% for each clinical

diagno-sis.

Lower respiratory tract infection appeared to

be a sensitive host response indicator of air

pollu-tion. Increased bronchitis in childhood may augur

increased morbidity and mortality in adulthood. Pediatrics, 47:391, 1971, AIR POLLUTION,

BRONCHI-TIS, INFANT, NITROGEN DIOXIDE, RESPIRATORY TRACT INFECTION, ENVIRONMENT.

D

U1UNG the Korean and Second World

Wars a substantial proportion of all

trmnitrotoluene (TNT) made in the United

States was produced by a plant located

northeast of Chattanooga, Tennessee, in

ru-ral Hamilton County. The plant was

re-opened in April, 1966 to supply munitions

for use in Vietnam. By then the facility was

bordered by upper-middle-class suburbs

whose residents soon began to complain

about the presence of fumes. Air quality

monitoring revealed elevated levels of

ni-trogen dioxide (NO2), a pollutant usually

associated with automotive and industrial

emissions.

Experiments in animals exposed to NO,

revealed changes in bronchiolar epithelium,

increased rates of Kiebsiella pneumoniae

infection and mortality, and an increased

susceptibility to tracheal infection with a

parainfiuenza virus.’ Prospective studies

conducted a year earlier in Hamilton

County revealed an increased rate of acute

upper respiratory illness in families living

in a high NO, area. The retrospective

study described here compares the

bronchi-tis, croup, and pneumonia in children

resid-ing in areas with varying degrees of NO2

air pollution.

MATERIALS AND METHODS

Area and Pollutant Exposure

Three areas were chosen to represent a

pollutant gradient on the basis of

aero-metric, meteorologic, and topographic

data.4’ These consisted of: a high NO,

cx-posure area surrounding the ammunition

plant, an intermediate NO, exposure area

seven miles southeast of the plant and

sepa-rated from it by low ridges, and a low NO2

exposure area located northwest of the plant

across the Tennessee River. Mean

inte-grated 24-hour NO, levels were .083 ppm

(parts per million) in the high exposure

area, .063 ppm in the intermediate exposure

area, and .043 ppm in the low exposure area

(Table I). The nitrate fraction of total

sus-pended particulates, another index of NO2

exposure, was 5.8 lJ.g/m3 in the high

expo-sure area, 2.6 g/m3 in the intermediate

ex-posure area, and 1.6 g/m3 in the low

ex-posure area. Total suspended particulate

concentrations were similar for all areas, as

(2)

ex-‘FABLE I

INTEGRATED 24-IIoUR SAMPLIR* Oi NITROGEN l)IoxIDE,

TOTAL SUSPENDED PARTICULATnS, SUSIENDED

NITUATK., AND SUSPENDED SULFATES

Total

NO, Sus- Sus-

Sn.,-Poll ulion (‘oncen- pended pended pended Gradient traI ions

/)/flfl

Nitrates

/.Lg/m3

Sulfates

g/m1

Particu-la/es

High

zg/m’

.083 5.8 11.5 81

IliterniedLIlte .063 El. 6 9. 8 7E2

Low .043 1.6 10.0 62

* Includes daily monitoring in November 1968 and

March 1969 and monitoring for one in 4 days from l)ecember 1968 through February 1969 and in April

1969.

ceed the thresholds currently associated

‘ith health impairment

(

Table I

)

.

Population

The age groups contacted in each area

were the first and second graders in public

elementary schools and all Caucasian

in-fants born during 1966, 1967, and 1968.

De-mographic data collected when the

partici-pating schools had cooperated in a previous

study characterized these areas as

upper-middle-class, white communities.4 Each

school child took home a questionnaire and

an explanatory letter; parents of infants

TABLE II

SCHOOL CHILDREN AND INFANT CoIIouT QUESTIONNAIRE

RESPONSE: DISTRIBUTION BY AREA

School Children in/ant Co/tort

Polluiion Percent Percent

Gradient Study Area

Population

Question-naire

Re-spondents*

Study Area

Population

(1970)f

Question

naire

Re-spondents’

111gb 731 94.3 541 86.3

Intermediate 491 90.3 350 85.1

Low 683 94.7 410 81.9

AH 1,906 05.0 1,311 84.4

#{149}Study area differences in questionnaire response were not sig-nificant; X2(s) =1.01 for school children and 3.65 for infants.

Does not include 477 infants who moved away from Chat-tanooga.

were contacted by mail. Response was

en-couraged by reminder notes, repeated

mail-ings, and telephones to non-respondents.

Among the infant cohorts, non-respondents

were assumed to have moved from

Chatta-nooga if they could not be located in the

cross-sectional index or the telephone

direc-tory, and/or if the post office returned their

questionnaires with no forwarding address.

A small percentage of respondents reported

they had moved from Chattanooga.

Questionnaire

The questionnaire inquired about the

fre-quency of treatment by a physician for

bronchitis

(

including bronchiolitis), croup,

or pneumonia during a 3-year period

begin-fling July 1966, shortly after the

ammuni-tion plant reopened. Total acute lower

re-spiratory infection ‘as defined as the sum

of the preceding three diagnoses.

Hospital-izations for lower respiratory infections,

his-tory of asthma, length of residence in the

area, and number of children in the family

were also ascertained. Hospital records

were searched to verify all reported

admis-sions and physicians’ records were reviewed

to validate a 14% sample of questionnaire

responses. The sample included equal

num-bers of well and sick children.

Statistical Testing

Hypotheses were tested by clii square

and ridit procedures.#{176}”

Response Rates

RESULTS

Among school children 95.0% of

qucs-tionnaires were completed and returned, an

excellent overall response

(

Table II).

Children in the intermediate NO2 area

re-turned 96.3% while the high and low

expo-sure areas returned 94.3 and 94.7%.

Al-though only two thirds of all questionnaires

mailed to parents of infants were returned,

this represented 84.6% of the group still

re-siding in Chattanooga since one quarter of

the population had moved away. Areas did

not differ significantly in the percentage of

(3)

TABLE III

NON-ASTHMATIC PARTICIPATING CHILDREN: DISTRIBU-TION BY LENGTH OF EXPOSURE

PERCENT OF CHILDREN REPORTING ONE OR MORE

EPISODES OF LOVER RESPIRATORY ILLNESS:

DISTRIBUTION BY LENGTH OF EXPOSURE

Pollution Gradient

School Children Years of Exposure

Infants Years of Exposure

ARTICLES 393

Asthma

As planned in the protocol, asthmatics

were excluded from the final analysis of

morbidity. In each area about 7% of the

children had a history of asthma. No area

differences in acute lower respiratory

dis-ease were observed among asthmatics

cx-cept for an isolated increase in the

preva-lence of bronchitis among the nine infant

asthmatics

living in the high exposure area for 2 years.

All Acute Lower Respiratory Infection

Since the source of the nitrogen dioxide

pollution had becn active for approximately

3 years, children were grouped according to

exposure of 1, 2, and 3 or more years

(

Ta-ble III

)

. The percentage of children

experi-encing one or more episodes of lower

respi-ratory

infection during the 3-year period

covered by the questionnaire was then

cal-culated; 45.7% of infants reported one or

more episodes as compared to 37.1% of

school children. Older infants, as expected,

were more frequently affected with 35.4%

of those age 1, 43.5 of those age 2, and

54.9% of those age 3 reporting at least one

lower respiratory infection. No significant

area differences were indicated for school

children or infants with respect to lower

respiratory infection incidence during any

exposure duration (Table IV). School

chil-dren of the intermediate NO, area

experi-enced the most illness at all exposure levels,

ranging from 38.6% among school children

exposed 1 year to 52.3% among those

ex-posed 2 years. However, infants from the

high and intermediate NO, areas

experi-enced somewhat more illness than those

from the low NO, area (Table IV).

Bronchitis

Twenty-eight percent of school children

reported one or more episodes of bronchitis

as compared to 36% of infants. Again, older

infants were niore frequently affected with

28% of those age 1, 34% of those age 2,

and 45% of those age 3 having at least one

such illness.

One or more episodes of bronchitis were

School Children Infants

Years of Exposure

1 2 3 1 2 3

High 163 75 397 105 128 156

Intermediate 114 44 266 84 78 95

Low 167 59 362 71 100 113

reported significantly more often by school

children residing for 2 (p = .02) and 3 (p

= .01) years in the high and intermediate

NO, areas (Table V). This pattern was not

consistent for infants. In no case

did

the

high

and intermediate exposure cohorts

differ significantly from each other. Almost

all parents of school children were unable

to date precisely the occurrence of

bronchi-tis episodes. Therefore, it was impossible to

separate illnesses occurring before

resi-dence in the exposure areas from illnesses

occurring thereafter, which confounded the

comparisons of children exposed for 1 or

even 2 years. A similar situation did not

ex-ist among infants 1 and 2 years of age since

their exposure was lifetime.

Croup

More infants, 18% more than school

chil-dren 14%, reported at least one croup episode

Older infants again were more frequently

TABLE IV

1 2 3 1 5 3

High 30.7 46.7 38.8 40.0 45.3 57.1

Intermediate 38.6 52.3 41.0 33.3 45.0 58.9

Low 33.5 33.9 33. 1 30.9 38.5 48. 7

(4)

TABLE V

PERCENT OF CHILDREN REPORTING ONE OR MORE

EPiSODES OF BRONCHITIS: DISTRIBUTION BY LENGTH

OF EXPOSURE*

. I ollution Gradient

1 5 3 1 2 3

high Intermediate Low

20.9 34.7 32.2

31.6 45.5 31.2

25.1 20.3 23.2

33.3 37.5 46.8

26.2 29.5 50.5

21.1 34.0 36.3

Area differences in bronchitis rates were signifi-cant for school children exposed for 2 years (x’, = 7.49, p = .02), and for 3 years (x’, = 8.57, p = .01).

‘I’ABLE VI

PERCENT OF CHILDREN REPORTING ONE OR MORE

EPISODES OF CROUP: DISTRIBUTION

HY LENGTh OF EXPOSURE*

. I olluiwn

Gradient

School Children Years of

,

7)O8h

high

Intermediate Low

1 5 3 1 5 3

11.7 18.7 14.1

13.2 20.5 13. 5

12.0 16.9 15.2

13.3 14.8 22.4

10. 7 14. 1 30. 9 12.7 16.0 19.5 * Area differences in rates were not significant.

TABLE VII

PERCENT OF CHILDREN REPORTING ONE OR MORE

EPISODES OF PNEUMONIA: DISTRIBUTION BY LENGTh!

OF EXPOSURE*

Io1lUtion Gradient

-___

153

1 2 .9

high 3.1 5.3 3.8 1.0 0.8 7.0

Intermediate 6.1 4.5 6.0 2.4 3.8 11.5

Low 3.1 6.8 4.7 1.4 6.0 4.4

* Area differences in rates were not significant.

affected with 12% of those age 1, 15% of

those age 2, and 24% of children age 3

re-porting croup.

No significant area differences were

found in the proportion of children

re-ported to have croup and no area trends

emerged

(

Table VI).

Pneumonia

Only 4.4% of infants and 4.6% of school

children reported an episode of pneumonia.

Older infants reported more pneumonia,

ranging from 1.5% of those exposed 1 year

to 3.3 and 7.4% of those exposed 2 and 3

years. No significant area differences or

suggestive trends appeared among children

reporting having pneumonia episodes

(Table VII).

Repeated Episodes of Acute Lower

Respiratory Illness

Q

uestionnaires were next analyzed to

identify a subpopulation that might be

more susceptible to pollution effects. This

population was defined as those children

re-porting

more than one episode of

pneumo-nia or at least three episodes of lower

respi-ratory

tract infection, bronchitis, or croup.

Significantly increased illness was found

among school children exposed for 2

(

p

.03) and 3 years

(

p = .02 ). This increase

followed the pollutant gradient only in

those exposed for 3 years

(

Table VIII).

Overall, 20% of school children and 23% of

infants were classed as repeaters.

Repeated Bronchitis

Fourteen percent of school children and

17.3% of infants had repeated bronchitis.

Statistically signfficant differences appeared

among school children reporting three or

more episodes of bronchitis with exposures

of 2 (p = .006) and 3 (p = .005) years

(Table IX). Among children exposed for 2

years, 14.7% in the high NO, area, 31.8%

in the intermediate NO, area, and 8.5% in

the low NO, area had repeated bronchitis.

Among those exposed for 3 years, 19.6% in

(5)

intermedi-TABLE VIII

PERCENT OF CHILDREN REPORTING Tii HER OR Mou H

EPISODES OF LOWER RESPIRATORY INFECTIONS:

DISTRIBUTION BY LENGTh OF

ARTICLES 395

ate area, and 11.0% in the low NO, area

re-ported

repeat episodes. No significant

in-creases in repeated bronchitis emerged

among infants in the high and intermediate

NO, areas although the high NO2 area had

the most repeaters for all exposure

dura-tions. Differences followed the pollution

gradient only in infants and school children

exposed for 3 or more years.

Repeated Croup

Seven percent of school children and

6.5% of infants had repeated croup.

Re-peated croup was more frequent in the high

and intermediate NO, areas in only three of

six exposure gradient comparisons

(

Table

X) . In no case did the proportion of

chil-dren with repeated croup follow the

expo-sure gradient. Furthermore, no significant

area differences were found.

Repeated Pneumonia

Pneumonia was a rare occurrence and

re-peat episodes of pneumonia even rarer.

Only 1.2% of school children and 0.9% of

infants were reported to have recurrent

pneumonia. Among this small group, the

low NO, area had relatively more repeaters

in four of the six possible exposure gradient

comparisons. No significant area differences

were found.

Ridit Analysis

The preceding chi square morbidity

anal-yses can be combined in a single ridit

anal-ysis in which area differences in the

pro-portion of children reported to have lower

respiratory illness and the frequency of their

attacks can be assessed simultaneously.

When this was done total acute lower

re-spiratory morbidity and bronchitis were

again found to be increased significantly

among school children living in the

inter-mediate and

high

exposure areas for 2 and

3 years. Acute bronchitis was also increased

significantly (p < .05) among infants in the

intermediate area exposed to NO2 for 3

years. This increase approached

signifi-cance (p = .09) and followed the pollution

.

Infants Years of Expoirure

1 2 .3 1 2 3

Highs Intermediate

Low

14. 1 18.7 2.5.4 21.9 36.4 22.2

15.0 15.3 16.9

20.0 2.5.8 32.7

9.5 15.4 37.9

14.1 18.0 ‘24.8

Area differences in rates were significant for school

children exposed for 2 years (x’(i) =7.63, p=.03) and

for 3years (x’o =8.34, p=.02).

gradient in the chi square analysis for

“re-peated episodes.”

Record Reviews

For each area, errors of diagnosis and

enumeration were estimated by reviewing

physicians’ records linked with a 14%

sam-ple of questionnaire responses. “True

ill-ness” was defined by the physician record.

Sensitivity,

the percentage of “true illness”

reported by questionnaire, and specificity,

the percentage of truly well children

like-wise reported, were then calculated (Table

XII). For bronchitis, neither sensitivity nor

TABLE IX

PERCENT OF CHILDREN REPORTING THREE OR MOIIE EPISODES OF BRONCHITIS: DISTRIBUTION BY LENGTH

OF EXPOSURE*

}‘ears of Expo.eure

1 2 3 1 2 2

High 8.6 14.7 19.6 14.3 21.9 25.6

Intermediate 15.8 31.8 16.5 7.1 9.0 24.2

Low 9.0 8.5 11.0 8.5 15.0 18.6

* Area differences in rates were significant for school

(6)

* Area differences did not follow the pollutant

TAB1E X

L’ERCENT 01. (hh1LuhsEN REPORTING ‘I’IIHEE OR MORE

EPISODES OF CROUI’: DISTRIBUTION BY LENGTH

OF EXPOSURE*

School Children lnfants

1 2 3 1 5 .3

high 4.9 5.3 7.3 3.8 7.0 7.7

Intermediate 7.9 13.6 7.9 -2.4 3.8 11.6

Low 4.2 8.5 6.6 5.6 7.0 7.1

* Area differences in rates were not significant.

specificity differed between areas. Overall,

sensitivity was 70.5% and specificity was

86.9%. School children and infants did not

differ significantly in either sensitivity or

specificity even though both measures were

7% higher among infants.

For croup, significant area differences

ap-peared only for sensitivity, which was

de-creased in the intermediate NO, area.

Al-though a significant sensitivity difference

was calculated for croup, this was based on

only 53 ill children. Overall sensitivity was

67.9% and specificity was 91.1.

For pneumonia, neither sensitivity nor

specificity differed among areas. The

high-est sensitivity and specificity, 90.0% and

97.5%, were reported for this category.

Only 99 children from all areas reported

hospitalization for a lower respiratory

infec-tion. Overall sensitivity was 72.1% and

TABLE XI

PERCENT OF ChILDREN REPORTING REPEAT EPISODES

OF PNEUMONIA I)IsTRIBUTI0N BY LENGTH

OF EXPOSURE*

School Children infants

Polution Gradient

1 2 3 1 2 3

High 0 0 0 0 0 1.3

Intermediate 1.8 2.3 1.1 0 0 4.2

Low 2.4 5.1 1.7 1 .4 0 0.9

specificity was 98.8%. Significant area

dif-ferences did not exist for either measure.

Once diagnostic errors were defined and

discarded, few pure enumeration errors

were found. No signfficant area differences

were found in overreporting or

underre-porting the number of episodes. In fact,

only 1.6% underreported and 2.3%

overre-ported. The median number was two for

overreported episodes and one for

underre-ported episodes.

DISCUSSION AND CONCLUSIONS

School children exposed for 2 or 3 years

to elevated ambient levels of NO, reported

increased bronchitis morbidity. The

rela-tionship between lower respiratory

in-fections and NO2 has not been studied

previously in humans but British studies

re-vealed increased rates of such infections

among infants exposed to sulfur oxides and

particulate pollution.’ Animal studies of

the effect of NO, upon host defense

mecha-nisms employed doses 30 to 600 times

higher than the threshold level suggested

by the present report. Rats exposed to 2.0

ppm NO, for 33 weeks showed bronchial

epithelial abnormalities; however, exposure

to 0.8 ppm of NO, for 33 months failed to

produce any epithelial changes.1 Valand’

reported that alveolar macrophage inter

feron production was inhibited by 25 ppm

for NO, and parainfiuenza infection was

fa-cilitated. Purvis described increased

infec-tion and mortality rates among mice

ex-posed to .5 ppm of NO, for 6 months prior

to challenge with a K. pneumoniae aerosol.2

Conversely, Buckleyl0 reported that 37 ppm

of NO2 for either 30 days or 48 hours

de-creased mortality and rate of infection in

mice exposed to mouse adapted PR8

influ-enza virus.

Since illnesses among school children

with exposures of 1 or 2 years could not be

placed with certainty during the period of

NO, exposure, such reports were difficult to

interpret. A health effect should be related

to an exposure over time. Since children,

and probably infants, reported an increased

bronchitis morbidity after 3 years of

(7)

TABLE XII

SPECIFICITY AND SENSITIViTY OF THE QUESTIONNAIRE

FOR EACH DIAGNOSTIC CATEGORY: DISTRIBUTION BY AREA*

#{149}Area difference in sensitivity and #{149}peei&itywere signi&ant only for croup (x’(t =6.05, p= .048).

ARTICLES 397

level to provide an effect may, in fact, be

about 3 years. An effect threshold may exist

for NO, as exposure to levels higher than

that in the intermediate area did not result

in a further increase in bronchitis.

In the previous study of NO, and upper

respiratory infections, the illness experience

of children in the intermediate and low NO,

areas did not differ. Both groups reported

significantly fewer infections than children

in the high NO, area.’ This disparity

be-tween studies might reflect a different

threshold for the upper and lower

respira-tory tracts with the incidence of lower

re-spiratory infection a more sensitive index of

NO, toxicity. British studies in areas

pol-luted with particulates and sulfur oxides

re-vealed an identical pattern.SC

Repeated episodes of bronchitis were

more frequent in school children living in

the intermediate and high NO, areas for 2

or more years. In addition, bronchitis from

these areas were more likely to suffer

re-peated episodes. However, infants had not

yet developed this pattern.

Physician office records, including those

of 145 bronchitis patients, 65 croup

pa-tients,

and 27 pneumonia patients, revealed

no area bias in sensitivity or specificity of

the questionnaire response and, thus,

anti-air pollution sentiment could hardly affect

reporting of bronchitis or pneumonia. Since

clinical diagnostic criteria might well vary

among physicians, the observed area

differ-ences in bronchitis morbidity could have

been due to diagnostic bias if families from

the different study areas consulted distinct

groups of physicians. However, this did not

occur because the 24 Chattanooga

physi-cians who cared for the study population

were centrally located and almost all cared

for children from all three study areas.

Moreover, it is unlikely that physician

diag-nostic bias would account for differences

during some exposure periods but not

oth-ers. The only significant area differences

oc-curred in the intermediate NO, area where

illness underreporting was counter to any

expected anti-air pollution bias. Pure

enu-meration errors were quite rare and of

small magnitude. The middle class parents

Pollution Gradient

Bronc

Sensi. tivity

hitis

Speci-ficity

Cro

Sensi. tivity

up

Speci-ficity

Pneu,

Sensi-livity

nonia

Sped. ficity

High 69.2 89.1 86.7 90.1 80.0 98i

Intermediate 70.8 91.4 50.0 93.5 100.0 99.1

Low 72.5 81.4 78.6 89.7 87.5 95.1

Overall 70.5 86.9 67.9 91.1 90.0 97.5

participating in this study were dependable

historians.

This study demonstrated the utility of

partitioning lower respiratory illness into

major components. Significant differences

in bronchitis morbidity could have been

oh-scured if only total lower respiratory

dis-ease had been considered. Obscuring of

dif-ferences might have been caused by the

significant underreporting of croup in the

intermediate exposure area.

Infants reported more of each type of

ill-ness than school children, confirming a

com-mon clinical observation.11 The increasing

rates of infection as infants grew older were

probably related to increased time at risk,

possible protection afforded by maternal

antibodies during the first few months of

life, and relative isolation during early

in-fancy.

SPECULATION AND RELEVANCE

Increasing and intensifying bronchitis

morbidity has both immediate and distant

consequences. Each needless illness taxes

an already overburdened medical care

sys-tern. More ominously, if Reid” is correct in

his warning that “the bronchitic child is the

father of the bronchitic man,” NO,

expo-sure may already be contributing to an

un-relenting rise in morbidity and mortality

associated with chronic obstructive

pulmo-nary disease.13

Additional investigations of lower

respi-ratory disease and nitrogen dioxide are

(8)

unwarranted delays in providing clear air

for our children. There are few TNT plants

but many power plants and a myriad of

au-tomobiles, all of which need effective NO,

emission controls. Programs to reduce NO,

emissions from federal TNT plants are

al-ready underway.

REFERENCES

1. Freeman, C. B., Crane, S. C., Stephens, R. J.,

and Furiosi, N. J.: Environmental factors in

emphysema and a model system with NO.

Yale J. Biol. Med., 40:566, 1968.

2. Ehrlich, B., and Henry, M. C.: Chronic toxic-ity of nitrogen dioxide I. Effect on resistance

to bacterial pneumonia. Arch. Environ. Health, 17:860, 1968.

3. Valand, S. B., Acton, J. D., and Mvrvils, Q.

N.: Nitrogen dioxide inhibition of viral in-duced resistance in aveolar monocytes. Arch.

Environ. Health, 20:303, 1970.

4. Shy, C. M., Creason, J. P., Pearlinan, M. E.,

McClain, K. E., Benson, F. B., and Young,

M. M.: The Chattanooga school children

study: Effects of community exposure to ni-trogen dioxide. I. Methods, description of

pollutant exposure and results of ventilatory

function testing. J. Air Pol. Control Ass., 20:

No. 8, 539, 1970.

5. Shy, C. M., Creason, J. P., Pearlman, M. E.,

McClain, K. E., Benson, F. B., and Young,

M. M. : The Chattanooga school children

study: Effects of community exposure to

ni-trogen dioxide. II. Incidence of acute

respi-ratory illness. J. Air Pol. Control Ass., 20,

No. 9, 582, 1970.

6. Bross, I. D. J.: How to use the ridit analysis.

Biometrics, 14: 18, 1958.

7. Grizzle, J. E., Stonier, C. F., and Koch, C. C.:

Analysis of categorical data by linear

mod-els. Biometrics, 25:489, 1969.

8. Douglas,

J.

W. B., and \Valler, R. E. : Air

poi-lution and respiratory infection in children.

Brit. Jour. Prey. Soc. Med., 20:1, 1966.

9. Lunn, J. E., Knowelden, J., and Handyside,

A.

J.:

Patterns of respiratory illness in Shef-field infant school children. Brit.

J.

Prey. Soc. Med., 21:7, 1967.

10. Buckley, R. D., and Loosli, C. C.: Effects of

nitrogen dioxide inhalation on germ-free

mouse lung. Arch. Environ. Health, 18:588,

1969.

11. Dingle, J. H., Badger, C. F., and Jordan, W. S.:

Illness in the home. Cleveland: The Press

of Western Reserve University, pp. 33-37, 1964.

12. Reid, D. D.: The beginnings of bronchitis.

Proc. Royal Soc. Med., 62:311, 1969.

13. Anderson, D. 0.: Chronic nontuberculous re-spiratory diseases. In Clark, D. W. and

Mac-Mahon, B., ed.: Preventive Medicine.

Lon-don: J. and A. Churchill Ltd., pp. 491-498,

(9)

1971;47;391

Pediatrics

Robert J. M. Horton

Martin E. Pearlman, John F. Finklea, John P. Creason, Carl M. Shy, Marion M. Young and