sensitivities of the forced oscillation technique and spirometry in the detection of airway...

1
S62 Oral Presentations/Paediatric Respiratory Reviews 12S1 (2011) S1S66 children) was found in children who only had respiratory tract lesions (atopic bronchial asthma). The following differences were found: – Children who had the first phenotype of bronchial asthma were more often artificially fed (27%) than children with atopic bronchial asthma (11.6%) (p < 0.1). – Children with atopic march were born from mothers who smoked during pregnancy 3 times more often (30%) than children with atopic bronchial asthma (11.2%) (p < 0.1). – The defective allele of CYP2C19 gene reliably dominated in the first phenotype compared to the second one (p < 0.05). Similar results were obtained for CYP2D6 gene of the first detoxication phase (p < 0.01). – Statistically reliable differences were also found for GSTT1 gene of the second detoxication phase; the defective allele was more often found in children with the atopic march than in children with atopic bronchial asthma (37% and 13% respectively, p < 0.01). Conclusion: The research has found a higher incidence of asthma- provoking factors such as artificial feeding and mother’s smoking during pregnancy in children with the atopic march. Besides, this group had genetic defects of the first and second phases of xenobiotics detoxication system; this is likely to cause differences in clinical presentation of bronchial asthma with phenotypes I and II. VII.2 Sensitivities of the forced oscillation technique and spirometry in the detection of airway hyperreactivity in asthmatic children D. Cz¨ ovek, F. Pet´ ak, Z. Nov´ ak. University of Szeged, Szeged, Hungary The detection of airway hyperreactivity (AH) following bronchoprovocation tests plays a key role in the diagnosis of asthma. The measurement of lung function by means of spirometry in young children is limited by their inability to cooperate. Alternatively, the forced oscillation technique (FOT) requires minimal patient cooperation and provides direct information on the airway and respiratory tissue mechanics. The FOT has gained increasing attention for the measurement of lung function in children, but its ability to facilitate the diagnosis of asthma has not been explored. We therefore set out to compare the sensitivities of lung function parameters obtained with the FOT and spirometry in the detection of AH following different airway challenges in asthmatic children. The FOT and spirometry were performed in 20 asthmatic children under baseline conditions and after inhalations of increasing doses of aerosolized histamine and methacholine (0.5–16 mg/ml, for 2 minutes) at an interval of 2 weeks. The respiratory system input impedance was measured by the FOT; the resistance at 6 Hz (R 6 ) and the average resistance between 4 and 24 Hz (R 4–24 ) were extracted from these recordings. Spirometry was used to obtain the volume in the first second of forced expiration (FEV 1 ) and a flow parameter (FEF 25–75 ). Short- and long-term variabilities of the measured indices were also determined. Following the provocations with both agonists, the FOT detected AH earlier than spirometry (p < 0.001 at 0.05 mg/ml for R 4–24 and R 6 and at 1 mg/ml for FEV 1 and FEF 25–75 after both agonists) with significant correlations between the corresponding parameters relating to the central (R 2 = 0.6 and 0.48 between R 4–24 and FEV 1 for methacholine and histamine, respectively) and peripheral airways (R 2 = 0.47 and 0.50 between R 6 and FEF 25–75 ). With regard to the greater variability in the FOT parameters (R 4–24 = 10.3%, R 6 = 11.3%; FEV 1 = 4.3%, FEF 25–75 =7.1%), the two approaches exhibited similar sensitivities in the assessment of AH, with R 4–24 proving to be most sensitive following both challenges. Our findings suggest that the FOT is at least as suitable as spirometry for the detection of AH in asthmatic children. Since the FOT requires less patient cooperation than spirometry, use of the FOT may impose less stress on the children and may lead to a decrease in the age at which AH can be detected. This beneficial feature of the FOT may improve the early diagnosis of asthma in the preschool age range. VII.3 Cytomegalovirus infection in immunocompetent wheezy infants: diagnostic value of CMV PCR in bronchoalveolar lavage fluid G. Cinel 1 , S. Pekcan 2 , E. Yalcin 1 , D. Dogru 1 , U. Ozcelik 1 , N. Kiper 1 . 1 Hacettepe University, Ihsan Dogramacı Children’s Hospital Pediatric Pulmonology, Ankara, Turkey; 2 Selcuk University Pediatric Pulmonology, Konya, Turkey Introduction: Cytomegalovirus (CMV) pneumonitis in immuno- competent hosts is uncommon but is being recognized more frequently, particularly when presenting as severe viral pneumonia. Due to airway caliber and compliance of the lung, infants develop airway obstruction easily during the course of respiratory tract infections. There are only limited numbers of reports about CMV infection associated with prolonged and intractable wheezing in immunocompetent infants. Aims: The aims of our study are to determine lower respiratory tract infections caused by CMV in immunocompetent wheezy infants, using polimerase chain reaction (PCR) in bronchoalveolar lavage fluid (BAL), to compare CMV PCR in BAL and in blood samples for diagnosis, and also to evaluate the benefits of antiviral gancyclovir therapy in these patients. Materials and Methods: We retrospectively investigated the files of patients referred to our hospital between January 2000 and July 2010, with persistent wheezing that could not be explained with any other reason and fiberoptic flexible bronchoscopy (FFB) applied and CMV PCR in BAL fluid performed. Cystic fibrosis was excluded in all patients with sweat chloride measurement, and also known humoral and cellular immunodeficiencies were ruled out with detailed immunologic investigations. FFB was done to all patients with 3.6 mm flexible pediatric bronchoscope (Olympus ® ). BAL was performed from the right middle lobe bronchus or the most affected bronchial segment and aspirated aliquotes were analyzed for routine bacterial cultures, PCR for respiratory viruses and also CMV PCR. Patients with CMV PCR positivity in BAL fluids were examined for CMV serology (IgM and IgG) and CMV PCR in blood samples. Results: In this 10.5 years period, 102 infants with persistent wheezing with no underlying disease and not responding to any medical therapy, and who had diffuse interstitial infiltration with or without atelectasis on chest radiographs and/or thoracal CT admitted to our hospital. We performed FFB to all to exclude any structural airway abnormality and investigated CMV PCR in BAL fluids with other diagnostic tests. In 51 patients, CMV PCR in BAL fluid were positive. Retrospectively, we could reach to the files of 29 patients (18 males, 11 females; mean age 12.1 months). The mean CMV viral load measured as CMV PCR in BAL fluid of these patients was 27,6927.9 copies/mL (151–2,070,000 copies/mL). Only 8 patients had CMV PCR positivity in blood samples (mean 2,026.3 copies/mL). We detected a positively directed but weak relation between BAL and blood CMV PCR values by Spearman correlation analysis (r = 0.041). CMV IgM was positive in 10 patients and CMV IgG was positive in 24 patients. 17 patients, who had severe respiratory symptoms with tachypnea and hypoxia, received gancyclovir therapy. 10 of these patients fully recovered, 5 of them had partial remission and 2 patients had no improvement. Conclusion: BAL CMV PCR is a valuable test for the diagnosis of lower respiratory tract infections caused by CMV in immunocompetent wheezy infants. Blood CMV PCR and serologic tests are not valuable as BAL CMV PCR in these patients. In selected patients in this group, gancyclovir therapy can be effective.

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S62 Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66

children) was found in children who only had respiratory tract

lesions (atopic bronchial asthma).

The following differences were found:

– Children who had the first phenotype of bronchial asthma

were more often artificially fed (27%) than children with atopic

bronchial asthma (11.6%) (p < 0.1).

– Children with atopic march were born from mothers who smoked

during pregnancy 3 times more often (30%) than children with

atopic bronchial asthma (11.2%) (p < 0.1).

– The defective allele of CYP2C19 gene reliably dominated in the

first phenotype compared to the second one (p < 0.05). Similar

results were obtained for CYP2D6 gene of the first detoxication

phase (p < 0.01).

– Statistically reliable differences were also found for GSTT1 gene

of the second detoxication phase; the defective allele was more

often found in children with the atopic march than in children

with atopic bronchial asthma (37% and 13% respectively, p < 0.01).

Conclusion: The research has found a higher incidence of asthma-

provoking factors such as artificial feeding and mother’s smoking

during pregnancy in children with the atopic march. Besides,

this group had genetic defects of the first and second phases of

xenobiotics detoxication system; this is likely to cause differences in

clinical presentation of bronchial asthma with phenotypes I and II.

VII.2

Sensitivities of the forced oscillation technique and spirometry

in the detection of airway hyperreactivity in asthmatic children

D. Czovek, F. Petak, Z. Novak. University of Szeged, Szeged, Hungary

The detection of airway hyperreactivity (AH) following

bronchoprovocation tests plays a key role in the diagnosis of asthma.

The measurement of lung function by means of spirometry in young

children is limited by their inability to cooperate. Alternatively,

the forced oscillation technique (FOT) requires minimal patient

cooperation and provides direct information on the airway and

respiratory tissue mechanics. The FOT has gained increasing

attention for the measurement of lung function in children, but its

ability to facilitate the diagnosis of asthma has not been explored.

We therefore set out to compare the sensitivities of lung function

parameters obtained with the FOT and spirometry in the detection

of AH following different airway challenges in asthmatic children.

The FOT and spirometry were performed in 20 asthmatic children

under baseline conditions and after inhalations of increasing doses

of aerosolized histamine and methacholine (0.5–16 mg/ml, for 2

minutes) at an interval of 2 weeks. The respiratory system input

impedance was measured by the FOT; the resistance at 6Hz (R6) and

the average resistance between 4 and 24Hz (R4–24) were extracted

from these recordings. Spirometry was used to obtain the volume

in the first second of forced expiration (FEV1) and a flow parameter

(FEF25–75). Short- and long-term variabilities of the measured indices

were also determined.

Following the provocations with both agonists, the FOT detected

AH earlier than spirometry (p < 0.001 at 0.05mg/ml for R4–24 and

R6 and at 1mg/ml for FEV1 and FEF25–75 after both agonists)

with significant correlations between the corresponding parameters

relating to the central (R2 = 0.6 and 0.48 between R4–24 and FEV1 for

methacholine and histamine, respectively) and peripheral airways

(R2 = 0.47 and 0.50 between R6 and FEF25–75). With regard to the

greater variability in the FOT parameters (R4–24 = 10.3%, R6 = 11.3%;

FEV1 = 4.3%, FEF25–75 = 7.1%), the two approaches exhibited similar

sensitivities in the assessment of AH, with R4–24 proving to be most

sensitive following both challenges.

Our findings suggest that the FOT is at least as suitable as spirometry

for the detection of AH in asthmatic children. Since the FOT requires

less patient cooperation than spirometry, use of the FOT may impose

less stress on the children and may lead to a decrease in the age at

which AH can be detected. This beneficial feature of the FOT may

improve the early diagnosis of asthma in the preschool age range.

VII.3

Cytomegalovirus infection in immunocompetent wheezy

infants: diagnostic value of CMV PCR in bronchoalveolar lavage

fluid

G. Cinel1, S. Pekcan2, E. Yalcin1, D. Dogru1, U. Ozcelik1, N. Kiper1.1Hacettepe University, Ihsan Dogramacı Children’s Hospital

Pediatric Pulmonology, Ankara, Turkey; 2Selcuk University Pediatric

Pulmonology, Konya, Turkey

Introduction: Cytomegalovirus (CMV) pneumonitis in immuno-

competent hosts is uncommon but is being recognized more

frequently, particularly when presenting as severe viral pneumonia.

Due to airway caliber and compliance of the lung, infants develop

airway obstruction easily during the course of respiratory tract

infections. There are only limited numbers of reports about CMV

infection associated with prolonged and intractable wheezing in

immunocompetent infants.

Aims: The aims of our study are to determine lower respiratory tract

infections caused by CMV in immunocompetent wheezy infants,

using polimerase chain reaction (PCR) in bronchoalveolar lavage

fluid (BAL), to compare CMV PCR in BAL and in blood samples for

diagnosis, and also to evaluate the benefits of antiviral gancyclovir

therapy in these patients.

Materials and Methods: We retrospectively investigated the files

of patients referred to our hospital between January 2000 and

July 2010, with persistent wheezing that could not be explained

with any other reason and fiberoptic flexible bronchoscopy (FFB)

applied and CMV PCR in BAL fluid performed. Cystic fibrosis was

excluded in all patients with sweat chloride measurement, and

also known humoral and cellular immunodeficiencies were ruled

out with detailed immunologic investigations. FFB was done to all

patients with 3.6mm flexible pediatric bronchoscope (Olympus®).

BAL was performed from the right middle lobe bronchus or the most

affected bronchial segment and aspirated aliquotes were analyzed

for routine bacterial cultures, PCR for respiratory viruses and also

CMV PCR. Patients with CMV PCR positivity in BAL fluids were

examined for CMV serology (IgM and IgG) and CMV PCR in blood

samples.

Results: In this 10.5 years period, 102 infants with persistent

wheezing with no underlying disease and not responding to any

medical therapy, and who had diffuse interstitial infiltration with

or without atelectasis on chest radiographs and/or thoracal CT

admitted to our hospital. We performed FFB to all to exclude any

structural airway abnormality and investigated CMV PCR in BAL

fluids with other diagnostic tests. In 51 patients, CMV PCR in BAL

fluid were positive. Retrospectively, we could reach to the files of

29 patients (18 males, 11 females; mean age 12.1 months). The

mean CMV viral load measured as CMV PCR in BAL fluid of these

patients was 27,6927.9 copies/mL (151–2,070,000 copies/mL). Only

8 patients had CMV PCR positivity in blood samples (mean 2,026.3

copies/mL). We detected a positively directed but weak relation

between BAL and blood CMV PCR values by Spearman correlation

analysis (r = 0.041). CMV IgM was positive in 10 patients and CMV

IgG was positive in 24 patients.

17 patients, who had severe respiratory symptoms with tachypnea

and hypoxia, received gancyclovir therapy. 10 of these patients fully

recovered, 5 of them had partial remission and 2 patients had no

improvement.

Conclusion: BAL CMV PCR is a valuable test for the diagnosis

of lower respiratory tract infections caused by CMV in

immunocompetent wheezy infants. Blood CMV PCR and serologic

tests are not valuable as BAL CMV PCR in these patients. In selected

patients in this group, gancyclovir therapy can be effective.