Impact of Prematurity and Severe Viral Bronchiolitis on Asthma Development at 6–9 Years

Figures & data

Figure 1 Flow chart of patients included in the study.

Table 1 Baseline Characteristics of the Three Groups of Children Included in the Study: Preterm and Full Term Admitted for Bronchiolitis and Preterm Controls without Admission for Bronchiolitis

	Preterm with Bronchiolitis Admission N=133	Full-Term with Bronchiolitis Admission N= 114	Preterm without Bronchiolitis Admission N=146	P-value
Age (years, mean)	6.6 ± 0.9	6.6 ± 0.8	7.0 ± 0.7	<0.001
Gestational age (weeks, mean)	33.1 ± 2.8		33.1 ±2.7	0.963
Gestational age < 32 weeks	32(24.8%)		32(27.1%)	0.175
Gestational age 32° to 33^6 weeks	42(44%)		41(38%)	0.366
Gestational age 34° to 36^6 weeks	53(56%)		67(62%)	0.366
Male sex	63 (47%)	76 (67%)	82(56%)	0.010
Breast feeding	90(76%)	82(78%)	108(80%)	0.761
Atopic dermatitis	35(34%)	50(44%)	36(27%)	0.020
Smoking during pregnancy	28(24.3%)	17(15.2%)	17(12%)	0.030
Passive smoking	56(47%)	39(35%)	61(43%)	0.159
Daycare attendance	55(57%)	73(72%)	77(58%)	0.04
Siblings < 5 years	62(54%)	59(58%)	61(43%)	0.05
Asthma
Mother	24(20%)	14(12%)	20(14%)	0.261
Father	1111 14(11%)	11(9.7%)	8 (5%)	0.216
Siblings	37(36%)	36(32%)	19(17%)	0.005
Atopy
Mother	29(24%)	27(24%)	28(19%)	0.649
Father	28 (23%)	33(29%)	23(16%)	0.040
Siblings	20 (18%)	36(32%)	27(26%)	0.070

Table 2 Comparison of the Incidence of Recurrent Wheezing, Hospitalizations and Maintenance Asthma Treatment, Among the Preterm and Full-Term Groups Admitted for Bronchiolitis and the Preterm Group without Admission for Bronchiolitis

	Preterm with Bronchiolitis Admission N=133	Full-Term with Bronchiolitis Admission N= 114	Preterm without Bronchiolitis Admission N=146	P-value
Recurrent wheezing	104(78%)	97(85%)	88(61%)	<0.001
Recurrent wheezing admission	42(32%)	23(20%)	32(22%)	0.080
Current asthma	36(27%)	17(16%)	22(15%)	0.040
Treatment with Inhaled corticosteroids	70(53%)	54(47%)	41(28%)	<0.001
Treatment with Montelukast	57(43%)	43(38%)	32(22%)	0.001

Table 3 Bivariate Analysis of Factors Associated with Recurrent Wheezing in Preterm and Full-Term Children with History of Admission for Bronchiolitis

	Recurrent Wheezing N =195	Not Recurrent Wheezing N =44	P-value	OR (CI95%)	Current Asthma N=52	Not Current Asthma N=195	P-value	OR (CI95%)
Male gender	116 (60%)	20 (46%)	0.111	1.7(0.9–3.3)	23(45%)	107(55%)	0.261	0.7 (0.3–1.4)
Prematurity	98 (50%)	27 (61%)	0.183	0.4(0.3–1.2)	35(68%)	97(50%)	0.040	2.2(1.1–4.6)
Breast feeding	137(78%)	32(82%)	0.524	0.7(0.3–1.8)	40(77%)	150(77%)	0.998	0.9 (0.4–1.8)
Atopic dermatitis	74(40,5%)	11(35,5%)	0.586	1.2(0.2.7)	21(41%)	82(42%)	0.915	0.9(0.4–2.1)
Aeroallergen sensitization	25(31%)	43(52,4%)	0.566	1.3(0.5–3.3)	24(46%)	72(37%)	0.406	1.4(0.6–3.1)
Day care attendance	110(68%)	14(50%)	0.04	2.1(1.0–4.6)	35(67%)	132(68%)	0.873	0.9(0.4–2.1)
Siblings < 5 years	96(55%)	23(64%)	0.303	0.7(0.3–1.4)	25(49%)	109 (56%)	0.430	0.7(0.4–1.5)
Passive tobacco exposure	81(46%)	34(43%)	0.714	1.1(0.6–1.9)	16(31%)	86 (44%)	0.192	0.6(0.3–1.3)
Maternal asthma	31(16%)	6(15%)	0.790	1.1(0,4–2.9)	10(19%)	27(14%)	0.415	1.5(0.6–3.9)
Maternal atopy	45(24%)	10 (24%)	0.923	0.9(0.4–2.1)	15(28%)	46(23%)	0.598	1.2(0.5–2.9)
Paternal asthma	24(13%)	1 (2.4%)	0.05	5.9(1.0–45.4)	13(25%)	15(7%)	0.030	4.1 (1.5–11.1)
Paternal atopy	37(20%)	14(18%)	0.553	5.9(0.8–44.6)	20(39%)	48(25%)	0.080	1.9(0.9–4.2)
Siblings with asthma	57(33%)	15(40%)	0.415	0.7(0.3–1.5)	21(39%)	57(29%)	0.269	1.6(0,7–3.5)
Siblings with atopy	48(27%)	14(37%)	0.247	0.6(0.3–1.3)	21(39%)	48(25%)	0.090	1.9(0.9–4.4)
Viral detection	175(94%)	32(82%)	0.01	3.5(1.2–9.6)	47(91%)	179(91%)	0.871	0.9(0.2–3.4)
Viral codetection	19(10%)	5(13%)	0.601	0.7(0.3–2.2)	10(20%)	16(8%)	0.040	2.8(1.0–7.8)
RSV detection	85(46%)	19(49%)	0.752	0.9. (0.4–1.8)	22(42%)	95(49%)	0.418	0.7(0.3–1.5)
HRV detection	48(26%)	8(21%)	0.476	1.3 (0.6–3.1)	19(36%)	37(19%)	0.030	2.3(1.1–5.2)
ICU admission during bronchiolitis	10(5%)	6(14%)	0.04	0.3(0.1–0.9)	7(13%)	6(3%)	0.010	5.1(1.3–20.2)

Table 4 Multivariate Test of Possible Risk Factors for Recurrent Wheezing by a Backward (LR) Stepwise Logistic Procedure in Preterm and Full-Term Children with History of Admission for Bronchiolitis

	P-value	Adjusted OR	95% Confidence Interval
Positive viral Detection	0.006	8.2	1.1–70.2
Paternal asthma	0.050	3.1	1.1–10.2
Day care centre attendance	0.010	2.8	1.2–6.4

Table 5 Bivariate Analysis of Factors Associated with Recurrent Wheezing and Asthma at 6–9 Years in Preterm Children with and without Admission for Bronchiolitis

	Recurrent Wheezing N =186	Not Recurrent Wheezing N =84	P-value	OR (CI95%)	Current Asthma N=57	Not Current Asthma N=213	P-value	OR (CI95%)
Male gender	100 (54%)	42 (50%)	0.566	1.2 (0.7–1.9)	17(45%)	77(50%)	0.329	0.7 (0.3–1.4)
Gestational age	32.9 (2.9)	33.7(2.1)	0.030		32.9(3.0)	33.3(2.6)	0.456
Prenatal steroids	65(39%)	29 (35%)	0.549	1.2(0.7–2.1)	19(37%)	78(37%)	0.996	1.0(0.4–2.3)
Admission for bronchiolitis	99(53%)	27(32%)	0.001	2.5 (1.5–4.3)	38(67%)	117(48%)	0.030	2.2 (1.1–4.6)
Neonatal respiratory distress syndrome	45(24%)	9(11%)	0.010	2.5 (1.8–5.5)	11(20%)	43(20%)	0.873	0.9(0.3–2.4)
Palivizumab	24(13%)	12(14%)	0.840	0.9 (0.4–2.0)	9(16%)	28(13%)	0.566	0.7 (0.2–2.5)
Neonatal mechanical ventilation	48(26%)	10(12%)	0.01	2.5 (1.2–5.3)	11(20%)	49(23%)	0.398	0.6 (0.2–1.8)
Chronic lung disease	15(8%)	0%	0.01	3.3 (1.4–7.6)	2(3%)	11(5%)	0.481	1.22(0.1–3.9)
Breast feeding	143(77%)	65(78%)	0.860	0.9 (0.5–1.8)	49(86%)	151(71%)	0.080	2.4 (0.9–6.7)
Atopic dermatitis	59(32%)	23(27%)	0.432	1.1 (0.7–2.4)	16(29%)	68(32%)	0.716	0.9 (0.4–1.9)
Aeroallergen sensitization	76(41%)	28(33%)	0.270	1.5 (0.7–2.9)	30(52%)	68(32%)	0.050	2.2 (0.9–5.1)
Day care attendance	113(61%)	44(52%)	0.200	1.4(0.8–2.53	33(58%)	123(58%)	0.949	0.9 (0.4–2.1)
Siblings < 5 years	87(47%)	43(51%)	0.577	0.9(0.5–1.5)	24(43%)	94(44%)	0.917	0.9 (0.4–2.0)
Passive tobacco exposure	84(45%)	36(43%)	0.714	1.1 (0.6–1.9)	24(42%)	89(42%)	0.995	0.99(0.5–2.1)
Maternal asthma	37(20%)	7(9%)	0.023	2.6 (1.1–6.8)	12(22%)	32(15%)	0.281	1.6 (0.6–4.1)
Maternal atopy	43(23%)	15(18%)	0.937	0.9 (0.5–1.9)	16(28%)	40(19%)	0.247	1.6 (0.7–3.8)
Paternal asthma	19(10%)	4(5%)	0.178	2.1 (0.7–6.5)	10(17%)	11(5%)	0.010	3.7 (1.2 −12.0)
Paternal atopy	39(21%)	14(17%)	0.553	1.2 (0.6–2.4)	19(33%)	40(19%)	0.050	2.2 (1.0–4.9)
Siblings with asthma	56(30%)	14(17%)	0.04	2.0 (1–4.3)	16(29%)	43(20%)	0.303	1.6 (0.6–3.9)
Siblings with atopy	48(26%)	8(21%)	0.496	1.3 (0.6–2.7)	19(36%)	37(19%)	0.135	2.0 (0.8–5.4)

Table 6 Multivariate Analysis of Possible Risk Factors for Recurrent Wheezing by a Backward (LR) Stepwise Logistic Procedure in Preterm and Preterm Children with and without History of Admission for Bronchiolitis

	P-value	Adjusted OR	95% Confidence Interval
Positive viral Detection during bronchiolitis	<0.001	7.2	3.1–15.7
Maternal asthma	0.03	2.9	1.1–7.4

Table 7 Comparison of Affirmative Responses to Core Questions for Asthma (from ISAAC Questionnaire for 6-7-Year-Old) Among the Preterm and Full-Term Groups Admitted for Bronchiolitis and the Preterm Group without Admission for Bronchiolitis, at 6–9 Years of Age

Isaac Questionnaire for Asthma Symptoms	Preterm with Bronchiolitis Admission N=133	Full-Term with Bronchiolitis Admission N= 114	Preterm without Bronchiolitis Admission N=146	P-value
Ever wheezing	105 (79%)	87 (76%)	93 (64%)	0.050
Wheezing in the last 12 months	36 (27%)	17 (15%)	20 (14.5%)	0.040
Speech limited due to wheezing in the last 12 months	16 (12%)	3 (2.5%)	8 (6%)	0.050
Ever asthma	41 (31%)	20 (18%)	20 (14%)	0.010
Wheezing due to exercise	23 (17.5%)	7(6%)	11 (8%)	0.020
Sleep disturbed due to wheezing ≥1 night per week	29 (22%	7 (6%)	12 (8%)	0.002

Table 8 Multivariate Test of Possible Risk Factors for Current Asthma by a Backward (LR) Stepwise Logistic Procedure in 6-9-Year-Old Preterm and Full-Term Children with History of Admission for Bronchiolitis

	P-value	Adjusted OR	95% Confidence Interval
Rhinovirus detection during bronchiolitis	0.010	3.3	1.3–8.2
Viral coinfection during bronchiolitis	0.010	4.4	1.4–14.0
Paternal asthma	0.005	5.1	1.6–15.9
Intensive care unit admission during bronchiolitis	0.007	8.8	1.8–43.4

Table 9 Multivariate Test of Possible Risk Factors for Current Asthma by a Backward (LR) Stepwise Logistic Procedure in 6-9-Year-Old Preterm Children with and without History of Admission for Bronchiolitis

	P-value	Adjusted OR	95% Confidence Interval
Admission for bronchiolitis	0.040	2.2	1.1–4.8
Paternal asthma	0.040	3.3	1.1–10.8

Table 10 Comparison of Lung Function Values Among Preterm and Full-Term 6-to-9-Year-Old Children Previously Hospitalised for Bronchiolitis and the Control Group of 6-to-9-Year-Old Preterm Children without Admission for Bronchiolitis

	Preterm with Bronchiolitis Admission	Full-Term with Bronchiolitis Admission	Preterm without Bronchiolitis Admission	P-value
FEV-1	102.3 ± 14.9	104.1 ± 11.0	104.7 ± 15.7	0.604
FVC	96.8 ± 13.4	97.5 ± 12.7	105.1 ± 54.0	0.536
FEV-1/FVC	105.3 ± 10.5	107.2 ± 8.0	106.7 ± 9.1	0.606
MEF 50	90.3 ± 27.1	92.4 ± 21.7	97.1 ± 25.8	0.214