Brain Natriuretic Peptid: The Reason of Respiratory Distress is Heart Disease or Lung Disease? Taylan S¸ahing¨ozl¨u MD, Ulas¸ Karadas¸ MD, Kayi Eliac¸ik MD, Ali Rahmi ¨ Bakiler MD, Nihal Ozdemir Karadas¸ MD, Muhammed Ali Kanik MD, Masaallah Baran MD PII: DOI: Reference:
S0735-6757(15)00065-0 doi: 10.1016/j.ajem.2015.02.005 YAJEM 54792
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
21 December 2014 2 February 2015 2 February 2015
Please cite this article as: S¸ahing¨ ozl¨ u Taylan, Karada¸s Ula¸s, Elia¸cik Kayi, Bakiler Ali ¨ Rahmi, Karada¸s Nihal Ozdemir, Kanik Muhammed Ali, Baran Masaallah, Brain Natriuretic Peptid: The Reason of Respiratory Distress is Heart Disease or Lung Disease?, American Journal of Emergency Medicine (2015), doi: 10.1016/j.ajem.2015.02.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT BRAIN NATRIURETIC PEPTID: THE REASON OF RESPIRATORY DISTRESS IS HEART DISEASE OR LUNG DISEASE?
Ulaş Karadaş1, MD Kayı Eliaçık1,MD
RI PT
Taylan Şahingözlü1, MD
SC
Ali Rahmi Bakiler1, MD,Prof Dr Nihal Özdemir Karadaş²,MD
NU
Muhammed Ali Kanık1,MD
MA
Masaallah Baran1,MD
Institution: 1: İzmir Tepecik Resarch Hospital, 2: Ege University Pediatrics
Text word count: Number of tables:
2573 -3-
-1-
Respiratory Distress, Brain Natriuretic Peptid, Heart Disease, Lung Disease
AC
Key words:
CE
Number of figures:
PT ED
Date of preparation: 21/12 /2014
Conflict of interest: The authors don’t have any conflict of interest Corresponding author:
Ulaş KARADAŞ 225 Sok. No: 59 Kat: 3 D: 6 Karesi BALIKESIR e- mail:
[email protected]
Phone: + 90 5055407144
ACCEPTED MANUSCRIPT
PT ED
MA
NU
SC
RI PT
Many cardiac disease states (ventricular septal defect (VSD), patent ductus arteriosus (PDA), coarctation of aorta, cardiomyopathy…etc ) can mimic the more common illnesses of childhood, such as bronchiolitis, reactive airway disease and sepsis (1). Acute bronchiolitis, one of the most common disease of this group, is most commonly seen in children under two years of age. Acute bronchiolitis which is characterized by cough, wheezing, tachypnea, retractions on the chest, prolonged expiration, is because of small airway obstruction caused by viral agents (2). Although echocardiography (ECO) is a good diagnostic tool for the diagnosis of congenital heart disease and ventricular dysfunction, it is not available in every clinic (3). Because of that a sensitive, reachable marker to aid in the recognition of heart disease and lung disease in children will be useful (1). Recently brain natriuretic peptide levels were found to be reliable test for the diagnosis of underlying cardiovascular disease in infants with respiratory distress (3). Nowadays, the usage of Brain Natriuretic Peptide (BNP) and N-terminal ProBNP (NT-proBNP) in children with congenital heart diseases, is increasing gradually (4-9). It seems to be reliable to use natriuretic peptides as a marker in children with congenital heart disease (10). Brain natriuretic peptides especially induce natriuresis, diuresis and vasodilatation and secreted mainly by cardiac myocytes in response to ventricular volume increase and pressure (11). BNP is first secreted as a pre-prohormone with 134 amino acids and then converts to proBNP which consists of 108 amino acids (12). ProBNP consists of inactive N-terminal proBNP and active BNP (12). Active form of BNP is released after the N-terminal part of the proBNP is cut off (12). In this prospective study, we sought to evaluate the effect of BNP as a marker to differentiate cardiac or lung related respiratory distress in patients who were hospitalized with acute bronchiolitis in infancy.
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MATERIALS AND METHODS: This study was performed at Izmir Tepecik Hospital Pediatrics Department between August 2012 and August 2013. Hospitalized 68 patients with respiratory distress accompanying acute bronchiolitis were enrolled to the study. Nineteen (%28) patients had congenital heart disease (9 patients had VSD, 4 patients had atrial septal defect and VSD, 2 patients had VSD and PDA) and cardiomyopathy (4 patients had dilated cardiomyopathy (DCMP)). Local ethical committee approved the study. Informed consents were taken from the parents. Thirty patients who admitted to hospital because of minor orthopedic and urologic problems and whose respiratory and cardiovascular examinations were normal were enrolled to the study as control group. The acute bronchiolitis was diagnosed with history and physical examination (2) and anterior posterior lung X-ray was performed to all of the patients. Except chronic lung disease and heart disease, the patients with chronic illnesses such as immune deficiency, renal failure, cerebral palsy etc and the patients with severe pneumonic infiltrations in lung x-ray were excluded. Respiratory scoring was performed according to the patients’ general appearance, respiration rate, heart rate and retractions on the chest wall in order to evaluate the severity of the disease (2). According to the respiratory scores the patients between 0-3 points classified as mild, 4-8 points as moderate, and 9 and above as severe bronchiolitis. The oxygen saturations at room air, heart rates and respiration rates are recorded. The blood samples of both patient and control group were obtained in ethylene diamino tetra acetate (EDTA) and aprotinin containing tubes. 3ml venous samples were taken and BNP levels were measured with electro-chemiluminescence immunoassay (ELISA)
ACCEPTED MANUSCRIPT
NU
SC
RI PT
immediately. ADVIA Centaur BNP lite reagent and Solid Phase kit was used. The echocardiographic evaluation was performed within the first 24 hour of BNP measurement. The echocardiographic evaluations (2-dimensions, M-mode) were performed by a pediatric cardiologist with Philips Ultrasound System and S8-3 probe. The conventional echocardiographic measurements were calculated according to the American Echocardiography Association recommendations (13). The left ventricular dimensions were measured on parasternal long axis with M mode ECO and ejection fraction (EF) and fractional shortening (FS) were calculated with Teicholz formulation (14). The effect of plasma BNP level to gender, age, heart rate was evaluated. Then the effect of BNP level to clinical findings (oxygen saturation, respiration rate, follow up duration and treatment), the presence of cardiac disease or heart failure. The analysis was performed by SPSS (Statistical Package for Social Sciences) 17.0 statistic program. The mean and standard deviations of digital values were calculated. MannWhitney U test was used to compare two groups because the groups were not homogenous. Kruskal-Wallis test was used to compare mean BNP levels of three groups (presence of heart
PT ED
MA
disease or not and control group). Ki-square test was used in categorical data and Fisher’s exact test was used when the expected numbers were lower. The findings were accepted significant if p is under 0,05.
RESULTS: A total of 68 patients (22 girls, %32) were enrolled to the study. The control group was consisted of 30 children and %27 (8) of them were girls. The patients and control groups
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mean age were 5,9 ±5,0 (1-26) and 6,5±5,4 months respectively and there were no significant difference in age and gender between these groups (p=0,82, p=0,89). The mean oxygen saturation, respiration rate, follow up duration were shown in table 1. Before oxygen therapy, 10 patients (%15) oxygen saturation was above %92. Twenty patients (%29) respiration rate was greater than 60/min and 11 (%16) patient hospitalized more than 10 days. It was observed that age (p=0,397), gender (p=0,187) and heart rate (p=0,240) had no significant effect on BNP levels. Subsequently the patient group and control group and the patients with heart disease or not were compared according to BNP levels. P value was 0,004 and 0,001 respectively. The differences between these groups were found significant. (Table 2) (Figure 1).The mean BNP levels of patients with heart disease were significantly higher. When the respiratory rates and respiratory scores were compared in patients with congenital heart disease and without congenital heart disease according to BNP levels, no significant difference was found (Table 3) . The BNP levels of 35 patient (11 of them had CHD) were taken again when they came to control after hospitalization. While the mean control BNP levels of patients with congenital heart disease was 210±50,5 pg/ml, it was 40±28 pg/ml in patients without congenital heart disease. By echocardiographic evaluation mean ejection fraction was found 68,3±8,3 (42-79) in patient group. The difference was found significant when the ejection fraction of patient with heart disease and patients with no heart disease were compared. The mean EF were 64,0±10,5, 70,0±6,7, p=0,007 respectively. The comparison of ≥10 days follow up to
S0735-6757(15)00065-0 doi: 10.1016/j.ajem.2015.02.005 YAJEM 54792
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
21 December 2014 2 February 2015 2 February 2015
Please cite this article as: S¸ahing¨ ozl¨ u Taylan, Karada¸s Ula¸s, Elia¸cik Kayi, Bakiler Ali ¨ Rahmi, Karada¸s Nihal Ozdemir, Kanik Muhammed Ali, Baran Masaallah, Brain Natriuretic Peptid: The Reason of Respiratory Distress is Heart Disease or Lung Disease?, American Journal of Emergency Medicine (2015), doi: 10.1016/j.ajem.2015.02.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT BRAIN NATRIURETIC PEPTID: THE REASON OF RESPIRATORY DISTRESS IS HEART DISEASE OR LUNG DISEASE?
Ulaş Karadaş1, MD Kayı Eliaçık1,MD
RI PT
Taylan Şahingözlü1, MD
SC
Ali Rahmi Bakiler1, MD,Prof Dr Nihal Özdemir Karadaş²,MD
NU
Muhammed Ali Kanık1,MD
MA
Masaallah Baran1,MD
Institution: 1: İzmir Tepecik Resarch Hospital, 2: Ege University Pediatrics
Text word count: Number of tables:
2573 -3-
-1-
Respiratory Distress, Brain Natriuretic Peptid, Heart Disease, Lung Disease
AC
Key words:
CE
Number of figures:
PT ED
Date of preparation: 21/12 /2014
Conflict of interest: The authors don’t have any conflict of interest Corresponding author:
Ulaş KARADAŞ 225 Sok. No: 59 Kat: 3 D: 6 Karesi BALIKESIR e- mail:
[email protected]
Phone: + 90 5055407144
ACCEPTED MANUSCRIPT
PT ED
MA
NU
SC
RI PT
Many cardiac disease states (ventricular septal defect (VSD), patent ductus arteriosus (PDA), coarctation of aorta, cardiomyopathy…etc ) can mimic the more common illnesses of childhood, such as bronchiolitis, reactive airway disease and sepsis (1). Acute bronchiolitis, one of the most common disease of this group, is most commonly seen in children under two years of age. Acute bronchiolitis which is characterized by cough, wheezing, tachypnea, retractions on the chest, prolonged expiration, is because of small airway obstruction caused by viral agents (2). Although echocardiography (ECO) is a good diagnostic tool for the diagnosis of congenital heart disease and ventricular dysfunction, it is not available in every clinic (3). Because of that a sensitive, reachable marker to aid in the recognition of heart disease and lung disease in children will be useful (1). Recently brain natriuretic peptide levels were found to be reliable test for the diagnosis of underlying cardiovascular disease in infants with respiratory distress (3). Nowadays, the usage of Brain Natriuretic Peptide (BNP) and N-terminal ProBNP (NT-proBNP) in children with congenital heart diseases, is increasing gradually (4-9). It seems to be reliable to use natriuretic peptides as a marker in children with congenital heart disease (10). Brain natriuretic peptides especially induce natriuresis, diuresis and vasodilatation and secreted mainly by cardiac myocytes in response to ventricular volume increase and pressure (11). BNP is first secreted as a pre-prohormone with 134 amino acids and then converts to proBNP which consists of 108 amino acids (12). ProBNP consists of inactive N-terminal proBNP and active BNP (12). Active form of BNP is released after the N-terminal part of the proBNP is cut off (12). In this prospective study, we sought to evaluate the effect of BNP as a marker to differentiate cardiac or lung related respiratory distress in patients who were hospitalized with acute bronchiolitis in infancy.
AC
CE
MATERIALS AND METHODS: This study was performed at Izmir Tepecik Hospital Pediatrics Department between August 2012 and August 2013. Hospitalized 68 patients with respiratory distress accompanying acute bronchiolitis were enrolled to the study. Nineteen (%28) patients had congenital heart disease (9 patients had VSD, 4 patients had atrial septal defect and VSD, 2 patients had VSD and PDA) and cardiomyopathy (4 patients had dilated cardiomyopathy (DCMP)). Local ethical committee approved the study. Informed consents were taken from the parents. Thirty patients who admitted to hospital because of minor orthopedic and urologic problems and whose respiratory and cardiovascular examinations were normal were enrolled to the study as control group. The acute bronchiolitis was diagnosed with history and physical examination (2) and anterior posterior lung X-ray was performed to all of the patients. Except chronic lung disease and heart disease, the patients with chronic illnesses such as immune deficiency, renal failure, cerebral palsy etc and the patients with severe pneumonic infiltrations in lung x-ray were excluded. Respiratory scoring was performed according to the patients’ general appearance, respiration rate, heart rate and retractions on the chest wall in order to evaluate the severity of the disease (2). According to the respiratory scores the patients between 0-3 points classified as mild, 4-8 points as moderate, and 9 and above as severe bronchiolitis. The oxygen saturations at room air, heart rates and respiration rates are recorded. The blood samples of both patient and control group were obtained in ethylene diamino tetra acetate (EDTA) and aprotinin containing tubes. 3ml venous samples were taken and BNP levels were measured with electro-chemiluminescence immunoassay (ELISA)
ACCEPTED MANUSCRIPT
NU
SC
RI PT
immediately. ADVIA Centaur BNP lite reagent and Solid Phase kit was used. The echocardiographic evaluation was performed within the first 24 hour of BNP measurement. The echocardiographic evaluations (2-dimensions, M-mode) were performed by a pediatric cardiologist with Philips Ultrasound System and S8-3 probe. The conventional echocardiographic measurements were calculated according to the American Echocardiography Association recommendations (13). The left ventricular dimensions were measured on parasternal long axis with M mode ECO and ejection fraction (EF) and fractional shortening (FS) were calculated with Teicholz formulation (14). The effect of plasma BNP level to gender, age, heart rate was evaluated. Then the effect of BNP level to clinical findings (oxygen saturation, respiration rate, follow up duration and treatment), the presence of cardiac disease or heart failure. The analysis was performed by SPSS (Statistical Package for Social Sciences) 17.0 statistic program. The mean and standard deviations of digital values were calculated. MannWhitney U test was used to compare two groups because the groups were not homogenous. Kruskal-Wallis test was used to compare mean BNP levels of three groups (presence of heart
PT ED
MA
disease or not and control group). Ki-square test was used in categorical data and Fisher’s exact test was used when the expected numbers were lower. The findings were accepted significant if p is under 0,05.
RESULTS: A total of 68 patients (22 girls, %32) were enrolled to the study. The control group was consisted of 30 children and %27 (8) of them were girls. The patients and control groups
AC
CE
mean age were 5,9 ±5,0 (1-26) and 6,5±5,4 months respectively and there were no significant difference in age and gender between these groups (p=0,82, p=0,89). The mean oxygen saturation, respiration rate, follow up duration were shown in table 1. Before oxygen therapy, 10 patients (%15) oxygen saturation was above %92. Twenty patients (%29) respiration rate was greater than 60/min and 11 (%16) patient hospitalized more than 10 days. It was observed that age (p=0,397), gender (p=0,187) and heart rate (p=0,240) had no significant effect on BNP levels. Subsequently the patient group and control group and the patients with heart disease or not were compared according to BNP levels. P value was 0,004 and 0,001 respectively. The differences between these groups were found significant. (Table 2) (Figure 1).The mean BNP levels of patients with heart disease were significantly higher. When the respiratory rates and respiratory scores were compared in patients with congenital heart disease and without congenital heart disease according to BNP levels, no significant difference was found (Table 3) . The BNP levels of 35 patient (11 of them had CHD) were taken again when they came to control after hospitalization. While the mean control BNP levels of patients with congenital heart disease was 210±50,5 pg/ml, it was 40±28 pg/ml in patients without congenital heart disease. By echocardiographic evaluation mean ejection fraction was found 68,3±8,3 (42-79) in patient group. The difference was found significant when the ejection fraction of patient with heart disease and patients with no heart disease were compared. The mean EF were 64,0±10,5, 70,0±6,7, p=0,007 respectively. The comparison of ≥10 days follow up to
