Quantitative analysis of inflammatory and adhesion molecules in lungs of neonates with chronic lung disease (bronchopulmonary dysplasia) receiving mechanical ventilation

Okamoto, Cristina T.; Oldenburg Neto, Carlos F.; Witkowski, Sandra Mara; Percicote, Ana Paula; Pasqualotto, Luca R.; Troiano, Gabriela; Almeida, Tammy; Souza, Cleber M.; Noronha, Lúcia de

doi:10.5935/1676-2444.20160042

Cristina T. Okamoto

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Carlos F. Oldenburg Neto

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Sandra Mara Witkowski

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Ana Paula Percicote

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Luca R. Pasqualotto

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Gabriela Troiano

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Tammy Almeida

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Cleber M. Souza

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

Lúcia de Noronha CORRESPONDING AUTHOR: Lúcia de Noronha, Pontifícia Universidade Católica do Paraná (PUCPR); Escola de Medicina; Laboratório de Patologia Experimental, Rua Imaculada Conceição, 1.155; Prado Velho, CEP: 80215-901; Curitiba-PR, Brasil, Phone: +55 (41) 3271-2264. e-mail: lnno@terra.com.br

Pontifícia Universidade Católica do Paraná (PUCPR), Paraná, Brazil

CORRESPONDING AUTHOR: Lúcia de Noronha, Pontifícia Universidade Católica do Paraná (PUCPR); Escola de Medicina; Laboratório de Patologia Experimental, Rua Imaculada Conceição, 1.155; Prado Velho, CEP: 80215-901; Curitiba-PR, Brasil, Phone: +55 (41) 3271-2264. e-mail: lnno@terra.com.br

Parameters	New CLD^* * :average ± standard deviation; (n = 5)	Without CLD^* * :average ± standard deviation; (n = 35)	p value
Number of alveoli	40.9 ± 15.1	57.7 ± 16.2	0.033^§ § Mann-Whitney non-parametric test (p < 0.05);
Alveolar perimeter^‡ ‡ square micrometers;	481.5 ± 182.4	611.3 ± 206.2	0.018^† † Ancova (p < 0.05) (gestational age adjustment).

Parameters	Total samples (n = 51)	Classic CLD (n = 11)	New CLD (n = 5)	Without CLD (n = 35)	p value
Gender^† † number of cases;
Female	33	6	4	23
Male	18	5	1	12	^{- -} - - not statistically significant data.
Gestational age (weeks)	27 (28.9 ± 2.6)^* * median (average ± standard deviation);	27 (27-34.5)^‡ ‡ median (min-max);	33 (27-34.5)^‡ ‡ median (min-max);	27 (25-33)^‡ ‡ median (min-max);	0.04^§ § Kruskal-Wallis non-parametric test (p < 0.05);
Birth weight (g) (n = 49/51)	1760 (972.9 ± 342.7)^* * median (average ± standard deviation);	1021 (685-1650) ^‡ ‡ median (min-max);	1340 (900-1760)^‡ ‡ median (min-max);	870 (515-1695)^‡ ‡ median (min-max);	0.03^§ § Kruskal-Wallis non-parametric test (p < 0.05);
1-minute Apgar score (n = 45/51)	3 (3.5 ± 2.7)^* * median (average ± standard deviation);	2.6 (1-5)^‡ ‡ median (min-max);	6 (1-8)^‡ ‡ median (min-max);	3.4 (1-8)^‡ ‡ median (min-max);	^{- -} - - not statistically significant data.
5-minute Apgar score (n = 47/51)	7 (5.9 ± 2.9)^* * median (average ± standard deviation);	6.2 (2-9)^‡ ‡ median (min-max);	8.4 (5-10)^‡ ‡ median (min-max);	5.5 (0-10)^‡ ‡ median (min-max);	^{- -} - - not statistically significant data.
Maternal age (years) (n = 48/51)	25 (25 ± 6.4)^* * median (average ± standard deviation);	26.2 (16-36)^‡ ‡ median (min-max);	29.8 (18-36)^‡ ‡ median (min-max);	24.1 (15-37)^‡ ‡ median (min-max);	^{- -} - - not statistically significant data.
Number of pregnancies (n = 50/51)^† † number of cases;
1 or 2	30	6	2	22
≥ 2	20	5	3	12	^{- -} - - not statistically significant data.

Follow-up prenatal visits (n = 50/51)^† † number of cases;
Yes	27	7	4	16
No	23	4	1	18	^{- -} - - not statistically significant data.
Hypertensive event in pregnancy (n = 50/51)^† † number of cases;
Yes	12	3	3	5
No	38	8	2	29	0.01^§§ §§ Pearson correlation;
Gestational diabetes (n = 51/51)^† † number of cases;
Yes	1	0	1	0
No	50	11	4	35	^{- -} - - not statistically significant data.
Chorioamnionitis (n = 49/51)^† † number of cases;
Yes	5	1	0	4
No	44	10	5	29	^{- -} - - not statistically significant data.
Premature amniotic sac disruption (n = 45/51)^† † number of cases;
Yes	15	1	1	13
No	30	9	4	17	^{- -} - - not statistically significant data.
Type of birth (n = 51/51)^† † number of cases;
Normal delivery	29	6	2	21
Cesarean delivery	22	5	3	14	^{- -} - - not statistically significant data.
Twin pregnancy (n = 51/51)^† † number of cases;
Yes	12	5	1	6
No	39	6	4	29	^{- -} - - not statistically significant data.

Parameters	Total samples (n = 51)	Classic CLD (n = 11)	New CLD (n = 5)	Without CLD (n = 35)	p value
Patent ductus arteriosus^† † number of cases;
Yes	15	10	2	3	^{- -} - - not statistically significant data.
No	36	1	3	32
Cardiopulmonary resuscitation^† † number of cases;
Yes	40	8	3	29	^{- -} - - not statistically significant data.
No	11	3	2	6
Antibiotic therapy^† † number of cases;
Yes	33	10	4	19	^{- -} - - not statistically significant data.
No	18	1	1	16
Surfactant replacement therapy^† † number of cases;
Yes	15	7	0	8	^{- -} - - not statistically significant data.
No	36	4	5	27
Necrotizing enterocolitis^† † number of cases;
Yes	11	7	2	2	0.0001^§§ §§ Pearson correlation;
No	40	4	3	33
Bronchopneumonia^† † number of cases;
Yes	12	6	0	6	0.0165^§§ §§ Pearson correlation;
No	39	5	5	29
Pulmonary hemorrhage^† † number of cases;
Yes	9	3	1	5	^{- -} - - not statistically significant data.
No	42	8	4	30
Pulmonary hypertension^† † number of cases;
Yes	7	2	1	4	^{- -} - - not statistically significant data.
No	44	9	4	31
Choking^† † number of cases;
Yes	28	6	1	21	^{- -} - - not statistically significant data.
No	23	5	4	14
Intracranial hemorrhage^† † number of cases;
Yes	11	4	2	5	^{- -} - - not statistically significant data.
No	40	7	3	30
Pneumothorax^† † number of cases;
Yes	3	1	0	2	^{- -} - - not statistically significant data.
No	48	10	5	33
Sepsis^† † number of cases;
Yes	24	11	4	9	0.0001^§§ §§ Pearson correlation;
No	27	0	1	26
Corrected gestational age (weeks)^* * :median (average ± standard deviation);	29 (29.7 ± 3.2)^* * :median (average ± standard deviation);	32 (29-39)^‡ ‡ median (min-max);	34 (28-36)^‡ ‡ median (min-max);	27 (25-33)^‡ ‡ median (min-max);	0.0002^§ § Kruskal-Wallis non-parametric test (p < 0.05);
Survival time (days)	3 (7.6 ± 10.7)^* * :median (average ± standard deviation);	23.4 (11-50)^‡ ‡ median (min-max);	12.4 (8-21)^‡ ‡ median (min-max);	1 (0-6)^‡ ‡ median (min-max);	0.0001^§ § Kruskal-Wallis non-parametric test (p < 0.05);
Cause of death^† † number of cases;
Sepsis	24	11	4	9
Intracranial hemorrhage	4	0	1	3
Perinatal asphyxia	11	0	0	11	^{- -} - - not statistically significant data.
Others	22	0	0	22

Parameters	Classic CLD^‡ ‡ mean (max-min)/median; (n = 11)	New CLD^‡ ‡ mean (max-min)/median; (n = 5)	Without CLD^‡ ‡ mean (max-min)/median; (n = 35)	p value
Mechanical ventilation (days)	12.9 (1-29)/1	3.4 (1-9)/1	1.4 (0.02-6)/2	- -
CPAP (days)	5.6 (0.04-19)/1	4.40 (1-8)/0	1.91 (0.04-5)/25	- -
Oxygen tent (days)	3.8 (1-30)/5	1.8 (1-5)/1	-/35	- -
Catheter oxygen therapy^† † number of cases; CPAP: continuous positive airway pressure; FiO2max: maximum fraction of inspired oxygen; PIPmax: maximum peak inspiratory pressure; PEEPmax: maximum positive end-expiratory pressure;				- -
Yes	1	1	0
No	10	4	35
Oxygen therapy (days)	21.36 (11-50)	10.40 (8-15)	1 (0.02-6)	< 0.001^§ § statistical analysis not significant (p > 0.017); Fisher test (Bonferroni correction).
FiO₂max (%)	95 (40-100)	85 (40-100)	98.57 (60-100)	- -
PIPmax (mmHg)	21.16 (18-30)	20 (20-20)	22.93 (17-35)	- -
PEEPmax (mmHg)	4.78 (4-5)	5 (5-5)	5 (5-6)	- -

Marker	Classic CLD (n = 11)	New CLD (n = 5)	Without CLD (n = 33)	p value^§ § Kruskal-Wallis non-parametric test (p < 0.05); p value is between classic and without CLD and new and without CLD.
Neutrophils count	3.11	1.49	0.59	< 0.001
CD20+	1.5	2.12	1.25	0.938
CD25+	0.3214	0.95	0.3839	0.04
CD45RO+	5.25	1.36	2	0.0004
CD14 (alveolar septum)	3	341.5	15	0.0523
CD14 (alveolar space)	2	61	11	0.138
CD4+	10.887	2.766	2.86	0.016
CD8+	0.472	2.5	3.991	0.17
CD74+	12.25	9.625	7.187	0.05
ICAM	0.106	0.6	0.4292	0.02
VCAM	0	0.2	1	0.076

[1] CORRESPONDING AUTHOR: Lúcia de Noronha, Pontifícia Universidade Católica do Paraná (PUCPR); Escola de Medicina; Laboratório de Patologia Experimental, Rua Imaculada Conceição, 1.155; Prado Velho, CEP: 80215-901; Curitiba-PR, Brasil, Phone: +55 (41) 3271-2264. e-mail: lnno@terra.com.br

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Quantitative analysis of inflammatory and adhesion molecules in lungs of neonates with chronic lung disease (bronchopulmonary dysplasia) receiving mechanical ventilation

Análise quantitativa de moléculas inflamatórias e de adesão em pulmões de neonatos com doença pulmonar crônica (displasia broncopulmonar) submetidos à ventilação mecânica

ABSTRACT

INTRODUCTION:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION: