Croup: An 11-Year Study in a Pediatric Practice

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VOLUME 71

#{149}

JUNE 1983#{149} NUMBER 6

Pediatrics

Croup:

An I 1-Year

Study

in a Pediatric

Practice

Floyd

W. Denny,

MD, Thomas

F. Murphy,

MD, Wallace

A. Clyde,

Jr,

MD, Albert

M. Collier,

MD, and Frederick

W. Henderson,

MD

In collaboration with R. S. Senior, MD, C. I. Sheafter, MD, W. G. Conley III, MD, and R. M. Christian, MD

From the Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill

ABSTRACT. The etiology and epidemiology ofcroup were

studied in a pediatric group practice over an 11-year period, 1964 to 1975. Croup was diagnosed in 951

in-stances in 6,165 cases of lower respiratory tract infection (LRI) studied. As census figures of the practice clientele were available, attack rates were calculated. The mci-dence of total LRI was highest in the first year of life. In contrast, the attack rate for croup was highest in the second year of life; the rate declined gradually after that age. Croup was not diagnosed in the first month of life. Boys were 1.43 times more likely to develop croup than were girls. Three hundred sixty agents were isolated from the 951 croup cases. The parainfluenza viruses accounted for 74.2% of all isolates; 65% of the parainfluenza isolates were classified as parainfluenza virus type 1. Respiratory syncytial virus, influenza viruses A and B, and Myco-plasma pneumoniae were the only other agents isolated in appreciable numbers. The propensity of various agents to produce croup symptoms in children with LRI due to specific microorganisms was 58% for parainfluenzae type 1, 60% for parainfluenzae type 2, and 29% for parainflu-enzae type 3; similar figures for the other agents varied from 5% to 16%. The role of the various agents in the etiology of croup varied with patient age and depended on the propensity of the agent to produce the croup syndrome and the frequency of isolation of the agent at that age. The parainfluenza viruses were the most impor-tant croup agents at all ages; respiratory syncytial virus caused croup in children less than 5 years of age whereas

Received for publication June 14, 1982; accepted Nov 2, 1982. Reprint requests to (F.W.D.) 535 Burnett-Womack Clinical Sciences Building, 229-H, University of North Carolina, Chapel Hill, NC 27514.

American Academy of Pediatrics.

the influenza viruses and M pneumoniae were significant causes of croup only in children more than 5 to 6 years old. Croup occurred predominately in late fall and early winter, times when the parainfluenza viruses, especially type 1, occurred most frequently. The epidemiology of croup differs from that of bronchiolitis, pneumonia, and tracheobronchitis; knowledge of this should be helpful to the clinician caring for children with LRI. Pediatrics

1983:71:871-876;

croup, lower respiratory tract infection,

parainfluenza virus.

Croup is one of the common manifestations of infection of the lower respiratory tract in children. It is a syndrome characterized by varying degrees of inspiratory stridor, cough, and hoarseness

re-suiting from obstruction in the region of the larnyx. The cause is generally considered to be a respiratory

virus, and parainfluenza virus type 1 is the agent

most frequently implicated. Most reported studies on the characteristics of croup have been from hospitalized patients and have consisted of

epide-miologic

and

clinical

descriptions

of

infections

(2)

3O

24 w

>-z

iLl

8

-I I 0

0 0 2

H

I

AGE

Fig 1. Age- and sex-specific attack rates of total lower

respiratory tract illness (LRI) and croup in pediatric group practice, Chapel Hill, NC, 1964 to 1975.

TABLE 1. Incidence of Croup by Patient Age and Sex,

Chapel Hill, NC, 1964 to 1975

adding

a

new dimension to our knowledge of the

epidemiology of croup.

MATERIALS AND METHODS

The study was performed between July 1964 and

June 1975 in the only private practice of pediatrics

in Chapel Hill, NC. All children seen in the practice

from

birth

to 15 years of age with lower respiratory

infections (LRI) were admitted to the study; the

specific criteria for characterization of these

ill-nesses have been described.1 Those cases

diagnosed

as croup, which consisted of hoarseness and a

bark-ing cough, with or without inspiratory stridor, are

included in the present report. Chest

roentgeno-grams and blood counts were done as clinically

indicated and are not included as a part of this

report. Blood was not drawn for serologic studies.

After parental consent was obtained, clinical and

epidemiologic data were obtained and the

orophar-ynx was cultured for viruses and mycoplasmas.

Detailed descriptions of the data collected, the

methods used to determine the practice census, and the techniques employed to isolate and identify

viruses and mycoplasmas have been published

pre-viously.2

RESULTS

From 1964 to 1975 the pediatric practice

in-creased from two pediatricians caring for 3,500 children to four pediatricians caring for 6,500

chil-dren. During the 11 years of the study, 6,165 cases of lower respiratory tract infection were investi-gated, of which 951 were diagnosed as croup. These cases form the basis for this report. The 951 epi-sodes were seen in 903 children or 1.05 episodes per child. Fever was present in 82.55% of cases. Twelve or 1.26% of the patients required hospitalization; the ages of the hospitalized children ranged from 7 to 50 months with an average age of 21 months.

Croup was the sole diagnosis in 93.7% of the cases. Eighteen children (1.9%) had associated tracheo-bronchitis; 29 (3.0%) also had wheezing and 13 (1.4%) had pneumonia.

Attack

Rates by Age and Sex

The age- and sex-specific attack rates of total

lower respiratory tract illness and croup in the

practice are shown in Fig 1. The incidence of total

LRI was highest during the first year of life; the

rate in the second 6 months was slightly higher

than that in the first 6 months. In contrast, the

attack rate for croup was highest in the second year

of life, 4.7/100 children per year, having risen from

2.4/100 children per year during the first 6 months.

Croup was not diagnosed in children in the first

month of life; there were six cases (1.50/100

chil-r-1-r-1

TOTAL LRi

cou

JI a t i --- . ..

0- 6- -2 2-3 3-4 4-5 5-6 6-9 9-12 12-15

6

2

MONThSI YEARS I

Age (yr) Incidence/100 Chil-then/yr (M/F)

Incidence by Sex (M#{247}F)

0-#{189}

#{189}-i

1-2 2-3 3-4 4-5 5-6 >6

2.76/2.01

4.95/2.86

5.60/3.66 3.55/2.63 2.55/1.60 1.69/1.16 1.15/0.92 0.47/0.44

1.37

1.73

1.53 1.35 1.59 1.46 1.25 1.07

All ages 1.82/1.27 1.43

dren per year) in the second month and 11 cases

(2.76/100 children per year) in the third month.

After the second year, the rate decreased gradually

so that after 6 years of age it was only 0.46/100

children per year. These incidence figures for LRI

and croup reflect the changing proportion of LRI due to croup at various ages. In children less than

6 months of age, 15% of LRI was diagnosed as

croup; from age 1 to 2 years the figure was 24%; between ages 2 to 6 years the percentage fell

grad-ually, and after 6 years of age only 9% of LRIs were

classified as croup.

As is shown in Fig 1 croup was predominately a

disease of male children. The age-specific relative

risk of boys as compared with girls is

shown

in

Table 1. Overall, boys were 1.43 times more likely

to develop croup than girls. Between the ages of 6

and 12 months, boys were at greatest risk, 1.73

times greater than girls.

The etiologic agents recovered from children with

croup during the study are shown in Table 2.

A

total of 360 agents were recovered from 358

pa-tients; two children with parainfluenzae type 1

in-fections were also infected with Mycoplasrna

pneu-moniae. The overall isolation rate was 37.6%; this

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TABLE 3. Distribution of Principal Agents Recovered from Children with Croup Patient Age (yr) Total Cases of Croup Cases of Croup with Isolates

Parainfluenza Virus* Respiratory

Syncytial Vis*

Influenza Viruses A and B*

Mycoplasma

pneumoniae*

Type 1 Type 2 Type 3

0-1 1-2 2-3 3-4 4-5 5-6 >6 169 25i 162 114 71 48 i36 53 91 72 51 29 24 40

24 (45) 4 (8) 6 (11)

34 (37) 7 (8) 24 (26)

44 (61) 2 (3) 14 (19)

29 (57) 4 (8) 6 (12)

15 (52) 6 (21) 3 (10)

10 (42) 4 (17) 7 (29)

17 (43) 4 (10) 3 (8)

9 (17) 6 (7) 11 (15) 6 (12) 4 (14) 0 0 4 (8) 5 (5) 0 3 (6) 1 (3) 3 (13) 9 (23) 1 (2) 5 (5) 1 (1) 1 (2) 0 0 5 (13)

All ages 951 360 173 (48) 31 (9) 63 (18) 36 (10) 25 (7) 13 (4)

* Values are number of isolates; percent of cases of croup with isolates is shown in parentheses.

TABLE 4. Occurrence

NC, 1964 to 1975*

of Croup in Children with Lower Respiratory Illnesses Due to Certain Agents, Chapel Hill,

. .

Parainfluenza Virus Respiratory. .

Syncytial Virus

Influenza Viruses

A and B

Mycoplasma

.

pneumoniae

Type 1 Type 2 Type 3

Patient Age (yr) No. % No. % No. % No. % No. % No. %

0-1 i-2 2-3 3-4 4-5 5-6 >6 42 55 65 44 30 16 49 57 62 68 66 50 63 35 6 66 9 78 6 33 8 50 7 86 5 80 11 36 47 47 36 22 21 19 26 13 51 39 27 15 37 12 91 10 79 8 71 15 42 14 30 13 15 0 27 0 13 31 11 45 10 0 18 17 11 9 18 22 78 12 5 20 12 42 12 8 17 6 15 0 19 0 162 3

All ages 301 58 52 60 218 29 355 10 159 16 242 5

* Values are number of total lower respiratory tract illnesses due to agent and percent of illnesses associated with

croup.

29%, in children less than 1 year and more than 6 years of age, respectively. Between these age

ex-tremes the isolation rate varied from 36% to 51% and was highest in the age group 5 to 6 years. The marked association of the parainfluenza viruses, especially type 1, with croup is reflected in these figures. This group of myxoviruses accounted for

74.2% of all isolates from our croup cases. The

smaller roles of respiratory syncytial virus (RSV), influenza viruses types A and B, and Mpneumoniae

are shown clearly. The small number of other agents isolated (19) emphasizes that croup is caused predominately by a relatively small group of respi-ratory agents.

TABLE 2. Etiologic Agents with Croup, Chapel Hill, NC,

Recovered from 1964 to 1975

Children

No. % Total

Parainfluenza virus type 1 Parainfluenza virus type 3 Respiratory syncytial virus Parainfluenza virus type 2

Influenza virus type A

Mycoplasma pneumoniae Influenza virus type B Miscellaneous viruses 173 63 36 31 13 13 12 19 48.1 17.5 10.0 8.6 3.6 3.6 3.3 5.3

Total 360 100

The

role of the

various agents in the etiology of croup varied with patient age. The distribution of the principal agents recovered from children of

different ages is shown in Table 3. The

parainflu-enza viruses were the predominant agents at all

ages, and there was little difference between age groups. In contrast, RSV caused croup in children less than 5 years of age but not in older children

whereas influenza viruses A and B and M

pneu-moniae were significant causes of croup only in

children more than 5 or 6 years old.

The propensity of the various agents to cause croup in children of different ages is shown in Table

4. In all children with LRI due to parainfluenzae

type 1, 58% had croup and this varied little by age.

Parainfluenzae type 2 was equally likely to cause croup in infected children of all ages. Only 29% of children with parainfluenzae type 3 infections had croup, again with little age variation. Infections

with RSV, influenza viruses A and B and M

pneu-moniae were much less likely to cause croup; even

though RSV and M pneumoniae were common

causes of LRI, they were relatively unimportant causes of croup.

Epidemic and Seasonal Occurrence

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U)

Ld

I-.

-J

0U)

Li.

0

LU

z

6-A Paroinfluenza virus type I

0-0

Porainfluenza vwuS type 2 o-o Parainfluenza virus type 3

.- -. Respirotory syncyticl virus

U)

LU

U)

20

Li.

0

100

LU

80

z

60

40

20

July Sept. Nov. Jan. March May

MONTH

Fig 2. Prevalence of cases of croup by month of

occur-rence in pediatric group practice.

I I I I I I I I I I I I

month of the year during the 1 1-year study is shown

in Fig 2. There

was a dramatic

increase

of croup

cases beginning in September, a peak was reached

in November, and the number of cases decreased

sharply

in December. Beginning in January

the

number of cases began to decrease more slowly and

this trend continued until late spring.

The

monthly prevalence of the four most

fre-quently isolated agents from croup patients offers

an explanation, at least in part, for this marked

seasonal occurrence (Fig 3). Croup due to the three parainfluenza viruses occurred more frequently during the fall. RSV had a midwinter peak and was found in increased numbers during the spring as well, probably accounting for many of the croup

cases at that time. Although M pneumonio,e

and

influenza types A and

B did

not appear to be

frequent causes of croup, the regular occurrence of

M pneumoniae during the fall and the frequent occurrence of influenza outbreaks during the winter probably influenced the seasonal distribution of croup cases as well.

The epidemic occurrence of croup cases is dem-onstrated in Fig 4, which shows the incidence of

cases in children 0 to 5 years of age over a period

of

1 1 years. This age group was chosen for

illustra-tion because 81% of croup cases occurred in

chil-dren less than 5 years of age. The arrows in Fig 4

mark

the

months in which there were ten or more

isolates of the parainfluenza viruses and show that

these agents were responsible for the largest

out-breaks. The peak in October 1971 is an exception

200

80

60

140

MONTH

Fig 3. Monthly prevalence of selected respiratory

vi-ruses isolated from children with croup in pediatric group

practice.

to this. During this month there were two isolations

of parainfluenza

type

1,

one of parainfluenza

type

2, one of M pneumoniae,

and

one adenovirus.

It

seems probable that this represents a peak primar-ily due to parainfluenza viruses and that the

effi-ciency

of isolating

these

agents

during

this

time

was less then optimal. This phenomenon occurred

several times during the study. In addition, there

were

other

smaller peaks in croup incidence for

which

no correlative

isolates

were

identified.

The

peak in

December

1965 was associated with several

isolations of parainfluenza type 3 and M

pneumo-niae.

The

peak

in

February

1969

was

associated

with a sharp outbreak of influenza and RSV infec-tions. The peak in December 1972

was

associated

with the frequent isolation of M pneumoniae.

The

January 1975 peak occurred during an outbreak of

influenza virus

and

RSV

infections.

The

peaks

in

May 1967 and October 1974 were associated with

so few isolations that no associations can be made.

Thus, of 15 sharp outbreaks of croup during the study, nine could be attributed to the parainfluenza

viruses and four to the influenza viruses, RSV or

Mpneumoniae.

There

were only two outbreaks

that

could not be associated with these agents. In April

1969 there were 14 isolates of parainfluenzae type

3 with no increase in occurrence of croup. This is

of interest and possibly reflects the weaker

associ-ation of parainfluenza type 3 with croup

than

is

seen with types 1 and 2.

DISCUSSION

Most published studies on croup are from

hospi-talized patients and report the association of this

syndrome with respiratory viruses, especially

par-ainfluenza type i.”

Although

these

studies

have

provided

valuable

information

concerning

the

(5)

1965 ‘ 1966 ‘ 1967 ‘ 1968 1969 1970 1971 1972 973 1974 ‘ 975

YEARS IN MONTHS

I I-.

z 0

Ui

a: 0

-I

I C) 0 0

0

U)

Ui

U)

0

Fig 4. Epidemic occurrence of croup in children aged 0 to 5 years in pediatric group practice. Arrows indicate months in which parainfluenza viruses were prevalent. Asterisks mark peaks when other agents were prevalent or when no agent was isolated in sufficient number to implicate it as cause of epidemic; see text.

a general population. The data reported by Foy et

al’2 are an exception to this and record the

mci-dence of croup in preschool-aged children belonging

to a prepaid medical care group in Seattle. In this study the attack rates were 5.2/1,000 children per year in the 0- to 5-month age group, 11.0 in the 6-to 1 1-month age group, 14.9 in the 1-year-old group, 7.5 in the 2- to 3-year-old group, and 3.1 in the 4-to 5-year old group. Comparable figures in the present study were 24.3, 39.7, 47.0, 31.2, and 14.5 or approximately 3 to 5 times higher than in the Seattle study. The reasons for this discrepancy are not clear, but procedural differences probably played a large role. It is of interest to note, however, that the relative incidence of croup in various age groups in both studies was similar, with the peak incidence in the 1- to 2-year-old group.

The parainfluenza viruses have been shown to be

the major cause of croup when etiologic studies

have been performed, especially parainfluenza type

1.1320

Type

2 produces croup symptoms in a high percentage of children with LRI due to this agent, but the relative infrequency of occurrence of type 2 makes it a less important cause of croup. Type 3, although less likely to cause croup in the infected child than are the two other parainfluenza viruses, is a more important cause of croup than type 2 because of the greater frequency of its occurrence. Parainfluenza virus type 4 was not isolated in our study.

In addition to the parainfluenza viruses, RSV and M pneurnoniae are the other common causes

of LRI in children.2’ The present studies support reported observations that these agents are less likely to cause croup than are the parainfluenza

viruses. Inasmuch as RSV is the most common

cause of LRI in small children and M pneumoniae

is the most common cause in children more than 5

years old, the clinician should be aware that these agents can and do cause croup.

The influenza viruses were relatively infrequent

causes of croup in our study. A number of articles in the literature report the severity of croup due to the influenza viruses,2227 but in our patients these agents were not recognized to cause croup more severe than that caused by the other agents. There

are anecdotal reports of all other respiratory viruses

as causes of croup, including the mumps virus,28

but these are infrequent. It should be noted that

the adenoviruses, important causes of upper and

lower respiratory tract infections in children, are

infrequent causes of croup.

It has been speculated that children who have

croup are at increased risk in later years for

devel-oping lung changes that result in decreased

pul-monary function.30’3’ The present study provides

base line incidence data that should be valuable in designing studies to evaluate this possibility.

IMPLICATIONS

AND RELEVANCE

Croup, along with tracheobronchitis,32

bronchiol-itis,2 and pneumonia,33 are syndromes caused by infections of the lower respiratory tract in children.

In general, the same group of microorganisms,

pri-manly respiratory syncytial virus, parainfluenza viruses types 1 and 3, and Mycoplasma pneumoniae,

(6)

with parainfluenza virus infections, especially type 1; it

occurs

mostly in boys, has a peak occurrence

in the second year of life, and occurs predominately

in the late fall and early winter. The characteristic

clinical and epidemiologic pictures of the syn-dromes caused by infections of the lower respiratory tract in children, especially croup, sbould be helpful to the clinician caring for children with these

com-mon and important infections.

ACKNOWLEDGMENTS

This work was supported by the Vaccine Development

Branch, National Institute of Allergy and Infectious

Dis-eases, NIH (contract PH 43-67-48); the US Army Medical

Research and Development Command (contract DADA 17-71-C-1095); and the National Heart, Lung, and Blood Institute, NIH (SCOR grant No. HL 19171-03).

We thank F. A. Loda, W. P. Glezen, A. S. Dajani, R.

I. Slotkin, R. P. Lipman, G. W. Fernald, N. F. Rodman,

and K. H. Fendt for their contribution to this work.

REFERENCES

1. Loda FA, Clyde WA Jr, Glezen WP et al: Studies on the

role of viruses, bacteria and M pneumoniae as causes of lower respiratory tract infections in children. J Pediatr

1968;72:161-176

2. Henderson FW, Clyde WA Jr, Collier AM, et al: The etio-logic and epidemiologic spectrum of bronchiolitis in pediat-nc practice. J Pediatr 1979;95:183-190

3. Feigin RD, Cherry JD (eds): Textbook of Pediatric Infectious

Diseases, Philadelphia, WB Saunders Co, 1981, vol 1, pp

146-155

4. Eller JJ: Attack rates for hospitalized croup in children in a military population: Importance of A2 influenza infection.

Pediatr Res 1972;6:386

5. Halzel A: Virus isolations from throats of children admitted to hospital with respiratory and other diseases, Manchester

1962-64. Br Med J 1965;1:614-619

6. Mufson MA: Viruses, Mycoplasma pneumoniae and bacteria associated with lower respiratory tract disease among in-fants. Am J Epidemiol 1970;91:192-202

7. Parrott RH: Clinical syndromes among children. Am Rev Respir Dis 1963;88:73-76

8. Parrott RH: Viral respiratory tract illnesses in children. Bull

NYAcad Med 1963;39:629-648

9. Chanock R: WHO respiratory disease survey in children: A serological study. Bull WHO 1967;37:363-369

10. Horn MEC: Respiratory viral infection in childhood: A survey in general practice, Roehampton 1967-1972. J Hyg

1975;74:157-168

11. Buchan KA, Marten KW, Kennedy DH: Etiology and epi-demiology of viral croup in Glasgow, 1966-1972. J Hyg

1974;73:143-150

12. Foy HM, Cooney MK, Maletzky AJ, et al: Incidence and

etiology of pneumonia, croup and bronchiolitis in pre-school children belonging to a prepaid medical care group over a four year period. Am J Epidemiol 1973;97:80-102

13. Bisno AL: An outbreak of acute respiratory disease in Trin-idad associated with para-influenza viruses. Am J Epidemiol 1970;9i:68-77

14. Hall CB, Geiman JM, Breese BB, et al: Parainfluenza viral infections in children: Correlation of shedding with clinical manifestations. J Pediatr i977;91:194-198

15. Downham MAPS, McQuillin J, Gardner PS: Diagnosis and

clinical significance ofparainfluenza virus infections in

chil-dren. Arch Dis Child i974;49:8-15

16. Gardner PS: Observations on clinical and immunofluores-cent diagnosis of parainfluenza virus infections. Br Med J 1971;2:7-12

17. Parrott RH: Acute respiratory diseases of viral etiology: III.

Myxoviruses: Parainfluenza. Am J Public Health

1962;52:907-917

18. McLean DM: Parainfluenza viruses in association with acute laryngotracheobronchitis, Toronto, 1960-61. Can Med

Assoc J 1961;85:290-294

19. McClean DM, Bach RD, Larke RPB, et al: Myxoviruses associated with acute larnygotracheobronchitis in Toronto,

1962-63. Can Med Assoc J 1963;89:1257-1259

20. Herrmann EC Jr: Experiences in laboratory diagnosis of parainfluenza viruses in routine medical practice. Mayo Clin

Proc 1970;45:i77-i88

21. Glezen WP, Loda FA, Clyde WA Jr, et al: Epidemiologic patterns of acute lower respiratory disease of children in a

pediatric group practice. J Pediatr i971;78:397-406

22. Kim HW, Brandt CD, Chanock RM, et al: Influenza A and B virus infection in infants and young children during the

years 1957-1976, abstract ad. Pediatr Res 1978;12:423 23. Howard JB: Influenza A2 virus as a cause of croup requiring

tracheotomy. J Pediatr 1972;81:i148-1150

24. Hall CB, Douglas RG Jr: Respiratory syncytial Virus and

influenza: Practical community surveillance. Am J Dis Child

1976;130:615-620

25. Parrott RH: Serious respiratory tract illness as a result of Asian influenza and influenza B infections in children. J

Pediatr 1962;61:205-2i3

26. Brocklebank JT: Influenza A infection in children. Lancet

1972;2:497-500

27. Forbes JA: Severe effects of influenza virus infection. Med

JAust 1958;2:75-79

28. Foy HM, et a!: Isolation of mumps virus from children with

acute lower respiratory tract disease. Am J Epidemiol 1971;94:467-472

29. Brandt CD: Infections in 18,000 infants and children in a controlled study of respiratory tract disease: I. Adenovirus

pathogenicity in relation to serologic type and illness syn-drome. Am J Epidemiol 1969;90:484-500

30. Burrows B, Knudson RI, Lebowitz MD: The relationship of

childhood respiratory illness to adult obstructive airway disease. Am Rev Respir Dis 1977;i15:751-760

31. Loughlin GM, Taussig LM: Pulmonary function in children with a history of laryngotracheobronchitis. J Pediatr 1979;94:365-369

32. Chapman RS, Henderson FW, Clyde WA Jr, et a!: The epidemiology of tracheobronchitis in pediatric practice. Am J Epidemiol 1981;i14:786-797

33. Murphy TF, Henderson FW, Clyde WA Jr, et al: Pneu-monia: An eleven year study in a pediatric practice. Am J

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1983;71;871

Pediatrics

W. Henderson, R. S. Senior, C. I. Sheaffer, W. G. Conley III and R. M. Christian

Floyd W. Denny, Thomas F. Murphy, Wallace A. Clyde, Jr, Albert M. Collier, Frederick

Croup: An 11-Year Study in a Pediatric Practice

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