Rationale: We have previously reported that early rhinovirus (RV) wheezing illnesses are the most robust predictor of asthma development at age 6 years in high-risk children in the Childhood Origins of ASThma (COAST) birth cohort study. We sought to assess the role of etiology and frequency of wheezing illnesses in asthma risk from ages 6 to 13 years. Methods: A total of 259 children were followed prospectively to age 6 years, and 217 were followed to age 13 years. A generalized additive logistic regression model (GAM) of asthma was fit for asthma diagnosed at ages 6, 8, 11, 13 years, with smooth terms for number of RV wheezing illnesses, number of non-RV wheezing illnesses, and their interaction. In the absence of significant interaction the main effect p-values are reported. Results: The number of RV wheezing episodes in early childhood was significantly associated with asthma at all ages (6 years: p<0.0001; 8 years: p<0.0001; 11 years: p=0.0006; 13 years: p=0.002). The number of non-RV wheezing episodes was not significantly associated with asthma (6 years: p=0.06; 8 years: p=0.09; 11 years: p=0.06; 13 years: p=0.33). Conclusion: RV wheezing illnesses remain an important predictor of asthma development in high-risk children and continued research efforts should focus on defining host and viral factors that promote wheezing RV illnesses in early childhood.

Abstract Conclusions Results

Background

Methods

Assessment of Wheezing Frequency and Viral Etiology on Childhood and Adolescent Asthma Risk Anderson HM, Lemanske RF, Evans MD, Gangnon RE, Gern JE, Jackson DJ

Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Wisconsin School of Medicine & Public Health, Madison, WI USA

Poster #355

•  We previously reported that rhinovirus (RV) wheezing illnesses are the most significant predictors of the subsequent development of asthma at age 6 years1.

•  A similar high-risk cohort has reported that the number of lower respiratory episodes in the first years of life, as opposed to the particular infectious trigger, are associated with asthma development2.

Research Question

What is the role of RV wheezing illnesses versus wheezing illnesses caused by other viruses in asthma

risk from ages 6 to 13 years?

Hypothesis The number of RV wheezing illnesses will be a more robust

predictor of asthma development and persistence. Supported by NIH Grants RO1 HL61879, PO1 HL70831, MO1 RR03186, T32 AI007635, and by grant UL1TR000427

We would also like to thank the COAST children, their families, and the

COAST research staff, for all of their efforts on this project.

Acknowledgments

• The number of RV wheezing episodes in early childhood was significantly associated with asthma risk between ages 6 & 13 years while number of non-RV wheezing episodes was not significantly associated with asthma risk

•  Our study demonstrated higher rates of viral detection (90%) compared with a similar high-risk cohort (65%)2 with detection of RV (48% vs. 23%) accounting for the majority of the discrepancy.

•  We hypothesize that the molecular techniques utilized in our study more robustly identify RV C, which may account for the discrepancy in RV detection rates.

§  Children at high risk for the development of asthma were studied prospectively from birth in the Childhood Origins of ASThma (COAST) study; 259 were followed to age 6 and 217 to age 13

§  The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase– PCR

§  The relationships of these virus-specific wheezing illnesses and frequency of wheezing illnesses to the development of asthma were analyzed using a generalized additive logistic regression model (GAM)

References 1Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 2008;178:667-72. 2BØNNELYKKE et al. Association between respiratory infections in early life and later asthma is independent of virus type. J Allergy Clin Immunol. 2015, May;136(1):81-86.e4.

RV−A

RV−C

RSV PI

V

MPV CoV Ad

V

Flu

EV

RV−B

No

Viru

s

Whe

ezin

g Ill

ness

es (%

)

0

5

10

15

20

25

0

5

10

15

20

25 •  478 wheezing illnesses documented in first 3 years of life

•  97% (465) with nasal specimens obtained

•  Respiratory viruses detected in 90% (420/465) of wheezing illnesses

•  RV was detected in 48% (223/465) of wheezing illnesses

Fig 1. Respiratory Viruses Detected During Wheezing Illnesses in First 3 Years of Life

The numbers in the circles represent the number of participants with each wheezing history. Shaded circles represent asthma risk.

Year 11 asthma rates

# Non−RV Wheezing Illnesses

# R

V W

heez

ing

Illne

sses

0 1 2 3 4 5 6 7 8

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

110

12

4

2

1

1

27

6

1

4

1

7

3

2

2

2

2

1

2

2

2

2

1

1

1

3

2

1

1

1

3

1

1

1

1

1

1

1

RV: P=0.0005Non−RV: P=0.06

Year 13 asthma rates

# Non−RV Wheezing Illnesses

# R

V W

heez

ing

Illne

sses

0 1 2 3 4 5 6 7 8

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

111

12

4

2

1

1

26

5

1

4

1

7

3

2

1

2

2

1

2

3

3

2

1

1

1

4

2

1

1

1

2

1

1

1

1

1

1

1

RV: P=0.003Non−RV: P=0.33

Year 6 asthma rates

# Non−RV Wheezing Illnesses

# R

V W

heez

ing

Illne

sses

0 1 2 3 4 5 6 7 8

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

135

12

5

2

1

1

34

9

1

4

1

9

3

2

2

3

2

1

2

3

3

2

1

1

1

4

2

1

1

1

3

1

1

1

1

1

1

1

RV: P<0.0001Non−RV: P=0.06

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

• RV wheezing illnesses remain an important predictor of asthma development in high-risk children

• Ongoing research efforts should focus on defining host and viral factors that promote RV wheezing illnesses in early life

Implications

Ast

hma

Ris

k

Fig 2. Number of RV Wheezing Illnesses vs Number of non-RV Wheezing Illnesses and Asthma Risk