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Genotypic bases for phenotypic differences in children with bronchial asthma
Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66
– long-term after-effects: scar fistula orifice, single or complex; bronchomalacia due to cartilage destruction; circumferential stenosis; and ultimate bronchiectasis development. There is an unresolved debate on the respective place of radiology vs endoscopy in detecting endobronchial involvement. Several semirecent publications focus on underestimation by X-ray – including chest CT-scan – compared to flexible bronchoscopy [2]. Nevertheless these studies provide little information about the usefulness of detecting minor lesions, as this does not modify the treatment regimen. More recent radiological techniques using 3D-rendering methods allow accurate detection of ETB, thus potentially restricting the need for FB examination [5]. However there is a serious limitation regarding dosimetry when serial studies are needed in children with active disease. The following principles are still widely admitted: 1. In children with no symptoms and normal chest X-ray there is no need for additional investigation if the diagnosis is made clear. 2. CT-scan is indicated first when the chest X-ray demonstrates hilar enlargement or mild parenchymal involvement; FB is next discussed if bronchial wall abnormalities or airway patency impairment are suspected. 3. CT-scan and bronchoscopy are both performed in the case of huge lymphadenomegaly, atelectasis or emphysema, and extended parenchymal infiltrates. 4. FB is indicated whatever the radiological status when bacteriological studies are positive. There is a large agreement for early detection of ETB in order to prevent late sequelae. Antituberculosis drugs show variable effect on lymph node volume; significant enlargement remains sometimes visible for several years irrespective of the antibacterial efficacy. Systemic corticosteroids are added to the 3 or 4 drugs regimen at the early phase of the process when severe extrinsic compression or endobronchial granulation are observed. Serial FB examinations are carried out in order to assess the response – ranging from one to several weeks – and to keep an eye on the occurrence of fistulization that can be promoted by steroids. Failure or worsening lead us to consider interventional procedures in order to restore the airway patency. Interventional bronchoscopy: Intractable airway obstruction can produce definitive pulmonary destruction. Surgical adenotomy has been proposed in order to relieve compression but carries the risk of severe postoperative complications. Tuberculous-infected tissues are weak in nature, bleed easily and show a strong tendency to break in the adjacent connective structures (including vessels) with no clear cleavage plane. Impairment of nutritional status often acts as a pejorative factor. Therefore, endoscopic debulking should always be attempted first. FB is not the most appropriate tool for this purpose except for suctioning mucus or caseum plugs. The rigid bronchoscope can be used by itself as a mechanical drill, by rotating and guiding the bevel through the narrowing structure. Various working instruments can be passed through the tube including endoscopic forceps and scissors, suction tubes, balloon-catheters, electrocautery probes, and laser-conducting optical fibres. Purely mechanical disobstruction maneuvers have the drawback of poor visualization due to induced bleeding and carry the risk of imprecise tissue resection (wall laceration, perforation, vascular injury). Interestingly, some laser beams exhibit specific properties that fit these constraints. The CO2 laser is one of them but it is cumbersome for use into the lower pediatric airway. In our experience the KTP laser is more suitable as the beam is carried on by optical fibres, the contact of which causes soft tissue coagulation and necrosis with shallow penetration and very precise cutting action (Fig. 2). Moreover the KTP wavelength interacts specifically with hemoglobin and thus provides perfect hemostasis. It is therefore a choice piece in the endoscopic armamentarium, allowing accurate photoresection of obstructive granulomas including tuberculous ones [6].
S61
Fig. 2. Endoscopic laser photoresection of tuberculous lymphadenopathy: (a) complete bronchus obstruction with right middle and lower lobes atelectasis; (b) bronchus recanalization leading to right lung reventilation; the KTP fibre can be seen at the bottom of the endoscopic picture (green light).
Cicatricial stenoses can be dilated using long-shape balloon catheters. Tracheobronchial stenting for post-tuberculous bronchomalacia has already been described but only in adult patients. References [1] Abadco DL, Steiner P. Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. Pediatr Infect Dis 19992; 11: 735–8. [2] Bibi H, Mosheyev A, Shoseyov D et al. Should bronchoscopy be performed in the evaluation of suspected pediatric pulmonary tuberculosis? Chest 2002; 122: 1604–8. [3] Gomes-Pastrana D, Torronteras R, Caro P et al. Diagnosis of tuberculosis in children using a polymerase chain reaction. Pediatr Pulmonol 1999; 28: 344–51. [4] Singh M, Ashan Moosa NV, Kumar L et al. Role of gastric lavage and broncho-alveolar lavage in the bacteriological diagnosis of childhood pulmonary tuberculosis. Indian Pediatr 2000; 37: 947–51. [5] Arlaud K, Gorincour G, Bouvenot J et al. Could CT scan avoid unnecessary flexible bronchoscopy in children with active pulmonary tuberculosis? A retrospective study. Arch Dis Child 2010; 95: 125–9. [6] Donato L, Tran TMH, Mihailidou E. Interventional bronchoscopy. In: Priftis KN, Anthracopoulos MB, Eber E, et al (eds). Paediatric bronchoscopy. Prog Respir Res. Basel, Karger 2010, vol. 38, pp. 64–74.
VII. Oral Communications from Young Investigators VII.1 Genotypic bases for phenotypic differences in children with bronchial asthma Y.B. Alimova1 , A.N. Galustyan1 , L.A. Jelenina1 , A.S. Glotov2 . 1 St.-Petersburg State Pediatric Medical Academy pulmonology, St.-Petersburg, Russia; 2 Research Institute of Obstetrics and Gynecology under the RAMN Genetics, St.-Petersburg, Russia Background: Bronchial asthma is a typical multifactorial disease. Its formation is genetically influenced by both “main” genes and “candidate” genes. Aim: To investigate the association between CYP2D6, CYP2C19 and CSTT1 genes polymorphisms and provoking factors to the peculiarities of bronchial asthma genotypes in children. Research methods: Bronchial asthma was diagnosed in 81 children; the diagnosis was based on GINA criteria (2009). The multiform variants of genes CYP2D6, CYP2C19 and CSTT1 were studied with the help of the PCR method in the prenatal diagnostics laboratory in Research Institute of Obstetrics and Gynecology. Results: On the grounds of clinical features, two phenotypes of bronchial asthma were found in children. The first phenotype (37 children) was bronchial asthma in combination with allergic rhinitis and atopic dermatitis (atopic march); the second phenotype (44
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 asthmaprovoking 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 6 Hz (R6 ) and the average resistance between 4 and 24 Hz (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 0.05 mg/ml for R4–24 and R6 and at 1 mg/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 . 1 Hacettepe University, Ihsan Dogramacı Children’s Hospital Pediatric Pulmonology, Ankara, Turkey; 2 Selcuk University Pediatric Pulmonology, Konya, Turkey Introduction: Cytomegalovirus (CMV) pneumonitis in immunocompetent 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.
– long-term after-effects: scar fistula orifice, single or complex; bronchomalacia due to cartilage destruction; circumferential stenosis; and ultimate bronchiectasis development. There is an unresolved debate on the respective place of radiology vs endoscopy in detecting endobronchial involvement. Several semirecent publications focus on underestimation by X-ray – including chest CT-scan – compared to flexible bronchoscopy [2]. Nevertheless these studies provide little information about the usefulness of detecting minor lesions, as this does not modify the treatment regimen. More recent radiological techniques using 3D-rendering methods allow accurate detection of ETB, thus potentially restricting the need for FB examination [5]. However there is a serious limitation regarding dosimetry when serial studies are needed in children with active disease. The following principles are still widely admitted: 1. In children with no symptoms and normal chest X-ray there is no need for additional investigation if the diagnosis is made clear. 2. CT-scan is indicated first when the chest X-ray demonstrates hilar enlargement or mild parenchymal involvement; FB is next discussed if bronchial wall abnormalities or airway patency impairment are suspected. 3. CT-scan and bronchoscopy are both performed in the case of huge lymphadenomegaly, atelectasis or emphysema, and extended parenchymal infiltrates. 4. FB is indicated whatever the radiological status when bacteriological studies are positive. There is a large agreement for early detection of ETB in order to prevent late sequelae. Antituberculosis drugs show variable effect on lymph node volume; significant enlargement remains sometimes visible for several years irrespective of the antibacterial efficacy. Systemic corticosteroids are added to the 3 or 4 drugs regimen at the early phase of the process when severe extrinsic compression or endobronchial granulation are observed. Serial FB examinations are carried out in order to assess the response – ranging from one to several weeks – and to keep an eye on the occurrence of fistulization that can be promoted by steroids. Failure or worsening lead us to consider interventional procedures in order to restore the airway patency. Interventional bronchoscopy: Intractable airway obstruction can produce definitive pulmonary destruction. Surgical adenotomy has been proposed in order to relieve compression but carries the risk of severe postoperative complications. Tuberculous-infected tissues are weak in nature, bleed easily and show a strong tendency to break in the adjacent connective structures (including vessels) with no clear cleavage plane. Impairment of nutritional status often acts as a pejorative factor. Therefore, endoscopic debulking should always be attempted first. FB is not the most appropriate tool for this purpose except for suctioning mucus or caseum plugs. The rigid bronchoscope can be used by itself as a mechanical drill, by rotating and guiding the bevel through the narrowing structure. Various working instruments can be passed through the tube including endoscopic forceps and scissors, suction tubes, balloon-catheters, electrocautery probes, and laser-conducting optical fibres. Purely mechanical disobstruction maneuvers have the drawback of poor visualization due to induced bleeding and carry the risk of imprecise tissue resection (wall laceration, perforation, vascular injury). Interestingly, some laser beams exhibit specific properties that fit these constraints. The CO2 laser is one of them but it is cumbersome for use into the lower pediatric airway. In our experience the KTP laser is more suitable as the beam is carried on by optical fibres, the contact of which causes soft tissue coagulation and necrosis with shallow penetration and very precise cutting action (Fig. 2). Moreover the KTP wavelength interacts specifically with hemoglobin and thus provides perfect hemostasis. It is therefore a choice piece in the endoscopic armamentarium, allowing accurate photoresection of obstructive granulomas including tuberculous ones [6].
S61
Fig. 2. Endoscopic laser photoresection of tuberculous lymphadenopathy: (a) complete bronchus obstruction with right middle and lower lobes atelectasis; (b) bronchus recanalization leading to right lung reventilation; the KTP fibre can be seen at the bottom of the endoscopic picture (green light).
Cicatricial stenoses can be dilated using long-shape balloon catheters. Tracheobronchial stenting for post-tuberculous bronchomalacia has already been described but only in adult patients. References [1] Abadco DL, Steiner P. Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. Pediatr Infect Dis 19992; 11: 735–8. [2] Bibi H, Mosheyev A, Shoseyov D et al. Should bronchoscopy be performed in the evaluation of suspected pediatric pulmonary tuberculosis? Chest 2002; 122: 1604–8. [3] Gomes-Pastrana D, Torronteras R, Caro P et al. Diagnosis of tuberculosis in children using a polymerase chain reaction. Pediatr Pulmonol 1999; 28: 344–51. [4] Singh M, Ashan Moosa NV, Kumar L et al. Role of gastric lavage and broncho-alveolar lavage in the bacteriological diagnosis of childhood pulmonary tuberculosis. Indian Pediatr 2000; 37: 947–51. [5] Arlaud K, Gorincour G, Bouvenot J et al. Could CT scan avoid unnecessary flexible bronchoscopy in children with active pulmonary tuberculosis? A retrospective study. Arch Dis Child 2010; 95: 125–9. [6] Donato L, Tran TMH, Mihailidou E. Interventional bronchoscopy. In: Priftis KN, Anthracopoulos MB, Eber E, et al (eds). Paediatric bronchoscopy. Prog Respir Res. Basel, Karger 2010, vol. 38, pp. 64–74.
VII. Oral Communications from Young Investigators VII.1 Genotypic bases for phenotypic differences in children with bronchial asthma Y.B. Alimova1 , A.N. Galustyan1 , L.A. Jelenina1 , A.S. Glotov2 . 1 St.-Petersburg State Pediatric Medical Academy pulmonology, St.-Petersburg, Russia; 2 Research Institute of Obstetrics and Gynecology under the RAMN Genetics, St.-Petersburg, Russia Background: Bronchial asthma is a typical multifactorial disease. Its formation is genetically influenced by both “main” genes and “candidate” genes. Aim: To investigate the association between CYP2D6, CYP2C19 and CSTT1 genes polymorphisms and provoking factors to the peculiarities of bronchial asthma genotypes in children. Research methods: Bronchial asthma was diagnosed in 81 children; the diagnosis was based on GINA criteria (2009). The multiform variants of genes CYP2D6, CYP2C19 and CSTT1 were studied with the help of the PCR method in the prenatal diagnostics laboratory in Research Institute of Obstetrics and Gynecology. Results: On the grounds of clinical features, two phenotypes of bronchial asthma were found in children. The first phenotype (37 children) was bronchial asthma in combination with allergic rhinitis and atopic dermatitis (atopic march); the second phenotype (44
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 asthmaprovoking 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 6 Hz (R6 ) and the average resistance between 4 and 24 Hz (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 0.05 mg/ml for R4–24 and R6 and at 1 mg/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 . 1 Hacettepe University, Ihsan Dogramacı Children’s Hospital Pediatric Pulmonology, Ankara, Turkey; 2 Selcuk University Pediatric Pulmonology, Konya, Turkey Introduction: Cytomegalovirus (CMV) pneumonitis in immunocompetent 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.