- Email: [email protected]
Question 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis?
G Model
YPRRV-1134; No. of Pages 2 Paediatric Respiratory Reviews xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Paediatric Respiratory Reviews
Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis? Dominic A. Fitzgerald MBBS PhD FRACP1,2,* 1 2
Department of Respiratory Medicine, the Children’s Hospital at Westmead, Sydney, NSW Australia Sydney Medical School, Discipline of Child and Adolescent Health, University of Sydney
For the last twenty-five years there has been an increasing emphasis on the early detection of airway infection and inflammation, mitigation with antibiotics and anti-inflammatory therapies and prevention or slowing of the progression of bronchiectasis in cystic fibrosis. There is clear evidence that the acquisition of Pseudomonas aeruginosa in sputum is a key adverse prognostic factor in the development of bronchiectasis and thereby in life expectancy [1–3]. Thus, the earlier detection and treatment of such airway pathogens in children who are unable to provide adequate sputum samples through the use of bronchoscopy is an attractive tool in the attempt to slow the evolution of bronchiectasis. The concept of a window of opportunity to mitigate early lung damage and maintain normal lung structure and function has gained popularity based upon findings from bronchoscopy, lung function testing and imaging [4–6]. Whilst differences in opinion exist as to the extent and reversibility of changes seen on CT imaging, there is broad agreement that changes are significant by the preschool years [7]. In this setting, bronchoscopy and bronchoalveolar lavage are key interventions in the care of young children with cystic fibrosis [CF] for the dual purposes of clinical assessment and research. In terms of clinical assessment, young children with cystic fibrosis may also experience anatomical airway problems such as laryngomalacia and tracheomalacia, with implications for further compromise to muco-ciliary clearance beyond that associated with CF alone [8]. Direct visualization of the proximal airway is important for diagnostic purposes as well as for sampling of sputum for airway pathogens with a broncho-alveolar lavage. One recent report has suggested a high frequency of tracho-malacia in children with CF and that the presence of tracheomalacia is associated with a lower forced expiratory volume in the first second of forced exhalation FEV1 and the presence of pseudomonas in the sputum [9]. Another indication for bronchoscopy is in the setting of surveillance post lung transplantation investigating for evidence
* Department of Respiratory Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales, Australia, 2145. Tel.: +61 2 9845 3397; fax: +61 2 9845 3396. E-mail address: dominic.fi[email protected].
of infection. Whilst lung transplantation is fortunately uncommon in the paediatric age range, figures suggest that people with CF do as well as children with other conditions requiring a lung transplant, with a median survival of 4.7 years [10]. In this setting, bronchoscopy is required for evaluation of anatomical complications such as bronchial stenosis at the anastomotic site and bronchoalveolar lavage and transbronchial biopsy areindicated as surveillance for cell counts and markers of rejection, culture for airway pathogens and anatomical evidence of rejection. The utility of bronchoalveolar lavage in obtaining sputum in infants and young children who are unable to expectorate is evident. In such a situation, bronchoalveolar lavage (BAL) is a clinically indicated intervention in young children who are often travelling along a familiar pathway of poor growth, recurrent bronchiolitis/bronchitis and persisting symptoms and signs of suppurative lung disease. The identification of positive sputum cultures will direct therapy and in all likelihood alter the clinical course. The practice of performing repeated routine surveillance bronchoscopies is popular in some centres but without evidence of benefit [11]. Indeed, the role of frequent bronchoalveolar lavage in the clinical setting was addressed in the landmark study of Wainwright and colleagues, who enrolled 170 infants with CF and randomized them to bronchoscopy/BAL guided therapy for each pulmonary exacerbation up to the age of five years or standard care [12]. The study failed to show any benefit in terms of higher isolation of pseudomonas from bronchoalveolar lavage samples compared to suction sputum/cough swab samples, and FEV1 and chest computerized tomography [CT] scan appearance at the age of 5 years. The cost of this approach was also higher by approximately $AUS 1900 over the five years [13]. In contrast to surveillance bronchoscopy in a stable child with CF, a suboptimal clinical course at any age warrants consideration of the role of resistant strains of pseudomonas aeruginosa or alternative pathogens such as atypical mycobacteria [14,15]. In a child who provides adequate sputum samples this may not be required. However, for the child with a suppressed cough, a diagnostic bronchoalveolar lavage may be of particular utility. Furthermore, the child with focal signs on physical examination or localized signs on chest imaging, may also benefit from a directed bronchoalveolar lavage [14,16,17]. The issue of sampling in BAL
http://dx.doi.org/10.1016/j.prrv.2016.05.005 1526-0542/ß 2016 Published by Elsevier Ltd.
Please cite this article in press as: Fitzgerald DA. Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis?. Paediatr. Respir. Rev. (2016), http://dx.doi.org/10.1016/j.prrv.2016.05.005
G Model
YPRRV-1134; No. of Pages 2 2
D.A. Fitzgerald / Paediatric Respiratory Reviews xxx (2016) xxx–xxx
has been previously addressed and in one study the concordance between two sites accessed [right middle lobe and lingula] for bacterial pathogens was about 75%, emphasizing the heterogeneity of CF lung disease [17]. With this in mind, one must always consider the more sites accessed and larger volumes of fluid washed will increase the risk of complications of the procedure [11]. Bronchoscopy should be undertaken or supervised by experienced hands as well as assisted by anaesthetists comfortable with the procedure [18]. The rates of adverse events following the bronchoalveolar lavage are common in CF infants as outlined by Wainwright et al. [19]. In this study they compared 170 subjects to age five years in the BAL directed therapy trial [12] at a median age of 27 months with 163 asymptomatic CF subjects at a median age of 10 months having a routine BAL and found that the major adverse event rate was high at 9% for a post-operative fever >38.5 deg C and was 3% for a period of oxygen desaturation <90% needing intervention during the procedure. Similarly, the minor adverse events were more common, with 41% of parents reporting an altered cough in their children and 12% of subjects having a low grade post-operative fever of <38.5 deg C.. In the clinical setting there are multiple other factors to consider. These begin with an explanation to families of the risks and benefits of the procedure in their child and their willingness for the procedure to be undertaken, the availability of anaesthetic time in the operating theatre and the optimal timing of the procedure in relation to the clinical setting. For example, in a persistently symptomatic young person with two negative sputum cultures in whom you may suspect pseudomonas aeruginosa, one would consider a bronchoalveolar lavage for culture. The important role of bronchoscopy in clinical research is evident. At a time of intense focus on early lung disease, with interventions to modify the clinical course, there is a need for comparative specimens to provide accurate information about the biomarkers of evolving lung disease in young children [20]. Biomarkers such as neutrophil elastase gathered from bronchoalveolar lavage specimens at the age of three months have been demonstrated to be predictive of the development of bronchiectasis on chest CT scan imaging at age three years [21]. Complementary roles of bronchoalveolar lavage and lung clearance index have been demonstrated in research studies of young children with CF [22]. The role of bronchoalveolar lavage findings in terms of neutrophil percentages and interleukin-8 concentration have complemented the clinical outcomes such FEV1 with the use of dornase alpha; where its anti-inflammatory properties have been described as attempts are made to better understand the pathophysiology of CF suppurative lung disease [23]. The diversity of the airway microbiome has come into focus and here the role of bronchoalveolar lavage has proven useful in highlighting the differences of the upper and lower airway: the greater diversity of organisms in the nose and throat as compared to the greater abundance of organisms in the lower airways [24]. This also serves a clinical purpose for distinguishing upper airway infection versus lower airway infection with pseudomonas- although the significance of this in the longer term with regard to the need for when to instigate intensive treatment has not reached consensus. Thus, as outlined by the European Cystic Fibrosis Clinical Trial Network Standardisation Committee, the research role of bronchoalveolar lavage remains central to studies that can help to ascertain the effectiveness of CF transmembrane regulators [CFTR] genetic modifiers, anti-inflammatory agents and antibiotics in infants and young children with CF in large centres with experience in this regard [11,18]. Similarly, the potential importance of longitudinal studies using bronchoalveolar lavage with various interventions remains as the alteration of biomarkers in the evolution of lung disease becomes clearer. There is no proven benefit for routine surveillance bronchoscopies in CF [11].
From a clinical viewpoint, the role of bronchoscopy and bronchoalveolar lavage remains clear with suspicions of airway anatomical abnormalities in young children, for children of any age who appear to have an unexplained clinical course and for patients following lung transplantation for which considerations of anastomotic compromise, infection and rejection remain paramount. Acknowledgement I would like to thank Associate Professor Hiran Selvadurai for his constructive review of the manuscript. References [1] Kosorok MR, Zeng L, West SHE, et al. Acceleration of lung disease in children with cystic fibrosis after pseudomonas acquisition. Pediatr Pulmonol 2001;32:277–87. [2] Kerem E, Viviani L, Zolin A, et al. Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS Patient Registry. European Respiratory Journal 2014;43:125–33. [3] Dijk FN, McKay KM, Barzi F, Gaskin KJ, Fitzgerald DA. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011. http://dx.doi.org/ 10.1136/archdischild-2011-300449 [4] Armstrong DS, Grimwood K, Carlin JB, et al. Lower Airway Inflammation in Infants and Young Children with Cystic Fibrosis. Am J Respir Crit Care Med 1997;156:1197–204. [5] Sly PD, Brennan S, Gangell C, deKlerk N, Murray C, Mott L, et al. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009;180:146–52. [6] Thia LP, Calder A, Stocks J, et al. Is Chest CT. useful in newborn screened infants with cystic fibrosis at 1 year of age? Thorax 2014;69:320–7. [7] Bush A, Sly PD. Evolution of cystic fibrosis lung function in the early years. Current Opinion in Pulmonary Medicine 2015;21:602–8. [8] Choo EM, Seaman JC, Musani AI. Tracheomalacia/tracheobronchomalacia and hyperdynamic airway collapse. Immunology and Allergy Clinics of North America 2013;33:23–34. [9] Fischer AJ, Singh SS, Adam RJ. et al Tracheomalacia is associated with lower FEV1 and Pseudomonas acquisition in children with CF. Ped Pulmonol 2014;49:960–70. [10] Kirkby S, Haynes Jr D. Pediatric lung transplantation: indications and outcomes. J Thorac Surg 2014;6:1024–31. [11] Fayon M, Kent L, Bui S, Dupont L, Sermet I. European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee. Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis. ERJ doi: 10.1183/09031936.00017713. [12] Wainwright CE, Vidmar S, Armstrong DS, et al. Effect of Bronchoalveolar Lavage-Directed Therapy on Pseudomonas aeruginosa Infection and Structural Lung Injury in Children with Cystic Fibrosis. A Randomized Trial. JAMA 2011;306:163–71. [13] Moodie M, Lal A, Vidmar S, et al. Costs of Bronchoalveolar lavage –directed therapy in the first five years of life for children with cystic fibrosis. J Pediatr 2014;165:564–9. [14] Gagliardo C, Saiman L. Microbiology of cystic fibrosis: Epidemiology of cystic fibrosis pathogens and clinical microbiology laboratory methods. Hodson and Geddes’ Cystic Fibrosis 2015;174. [15] Leung JM, Oliver KN. Nontuberculous mycobacteria in patients with cystic fibrosis. In Seminars in respiratory and critical care medicine 2013;34:124–34. [16] Gilchrist FJ, Salamat S, Clayton S, Peach J, Alexander J, Lenney W. Bronchoalveolar lavage in children: how many lobes should be sampled? Arch Dis Child 2011;96:215–7. [17] Gutierrez JP, Grimwood K, Armstrong DS, et al. Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis. Eur Respir J 2001;17:281–6. [18] Faro A, Wood RE, Schechter MS, Leong AB, Wittkugel E, Abode K, et al. Official American Thoracic Society technical standards: flexible airway endoscopy in children. Am J Respir Crit Care Med 2015;191:1066–80. [19] Wainwright CE, Grimwood K, Carlin JB, et al. Safety of bronchoalveolar lavage in young children with cystic fibrosis. Pediatr Pulmonol 2008;43:965–72. [20] Ramsey K, Schultz A, Stick SM. Biomarkers in Pediatric Cystic Fibrosis Lung Disease. Pediatr Respir Rev 2015. http://dx.doi.org/10.1016/j.prrv.2015.05.004. [21] Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, et al. Risk Factors for Bronchiectasis in Children with Cystic Fibrosis. N Eng J Med 2013;368:1963–70. [22] Belessis Y, Dixon B, Hawkins G, et al. Early Cystic Fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index. Am J Respir Crit Care Med 2012;185:862–73. [23] Paul K, Rietschel E, Ballmann M, et al. Effect of Treatment with Dornase Alpha on Airway Inflammation in Patients with Cystic Fibrosis. Am J Respir Crit Care Med 2004;169:719–25. [24] Boutin S, Graeber SY, Weitnauer M, et al. Comparison of Microbiomes from Different Niches of Upper and Lower Airways in Children and Adolescents with Cystic Fibrosis. PLOSONE/DOI:10.1371/journal.pone.0116029.
Please cite this article in press as: Fitzgerald DA. Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis?. Paediatr. Respir. Rev. (2016), http://dx.doi.org/10.1016/j.prrv.2016.05.005
YPRRV-1134; No. of Pages 2 Paediatric Respiratory Reviews xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Paediatric Respiratory Reviews
Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis? Dominic A. Fitzgerald MBBS PhD FRACP1,2,* 1 2
Department of Respiratory Medicine, the Children’s Hospital at Westmead, Sydney, NSW Australia Sydney Medical School, Discipline of Child and Adolescent Health, University of Sydney
For the last twenty-five years there has been an increasing emphasis on the early detection of airway infection and inflammation, mitigation with antibiotics and anti-inflammatory therapies and prevention or slowing of the progression of bronchiectasis in cystic fibrosis. There is clear evidence that the acquisition of Pseudomonas aeruginosa in sputum is a key adverse prognostic factor in the development of bronchiectasis and thereby in life expectancy [1–3]. Thus, the earlier detection and treatment of such airway pathogens in children who are unable to provide adequate sputum samples through the use of bronchoscopy is an attractive tool in the attempt to slow the evolution of bronchiectasis. The concept of a window of opportunity to mitigate early lung damage and maintain normal lung structure and function has gained popularity based upon findings from bronchoscopy, lung function testing and imaging [4–6]. Whilst differences in opinion exist as to the extent and reversibility of changes seen on CT imaging, there is broad agreement that changes are significant by the preschool years [7]. In this setting, bronchoscopy and bronchoalveolar lavage are key interventions in the care of young children with cystic fibrosis [CF] for the dual purposes of clinical assessment and research. In terms of clinical assessment, young children with cystic fibrosis may also experience anatomical airway problems such as laryngomalacia and tracheomalacia, with implications for further compromise to muco-ciliary clearance beyond that associated with CF alone [8]. Direct visualization of the proximal airway is important for diagnostic purposes as well as for sampling of sputum for airway pathogens with a broncho-alveolar lavage. One recent report has suggested a high frequency of tracho-malacia in children with CF and that the presence of tracheomalacia is associated with a lower forced expiratory volume in the first second of forced exhalation FEV1 and the presence of pseudomonas in the sputum [9]. Another indication for bronchoscopy is in the setting of surveillance post lung transplantation investigating for evidence
* Department of Respiratory Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales, Australia, 2145. Tel.: +61 2 9845 3397; fax: +61 2 9845 3396. E-mail address: dominic.fi[email protected].
of infection. Whilst lung transplantation is fortunately uncommon in the paediatric age range, figures suggest that people with CF do as well as children with other conditions requiring a lung transplant, with a median survival of 4.7 years [10]. In this setting, bronchoscopy is required for evaluation of anatomical complications such as bronchial stenosis at the anastomotic site and bronchoalveolar lavage and transbronchial biopsy areindicated as surveillance for cell counts and markers of rejection, culture for airway pathogens and anatomical evidence of rejection. The utility of bronchoalveolar lavage in obtaining sputum in infants and young children who are unable to expectorate is evident. In such a situation, bronchoalveolar lavage (BAL) is a clinically indicated intervention in young children who are often travelling along a familiar pathway of poor growth, recurrent bronchiolitis/bronchitis and persisting symptoms and signs of suppurative lung disease. The identification of positive sputum cultures will direct therapy and in all likelihood alter the clinical course. The practice of performing repeated routine surveillance bronchoscopies is popular in some centres but without evidence of benefit [11]. Indeed, the role of frequent bronchoalveolar lavage in the clinical setting was addressed in the landmark study of Wainwright and colleagues, who enrolled 170 infants with CF and randomized them to bronchoscopy/BAL guided therapy for each pulmonary exacerbation up to the age of five years or standard care [12]. The study failed to show any benefit in terms of higher isolation of pseudomonas from bronchoalveolar lavage samples compared to suction sputum/cough swab samples, and FEV1 and chest computerized tomography [CT] scan appearance at the age of 5 years. The cost of this approach was also higher by approximately $AUS 1900 over the five years [13]. In contrast to surveillance bronchoscopy in a stable child with CF, a suboptimal clinical course at any age warrants consideration of the role of resistant strains of pseudomonas aeruginosa or alternative pathogens such as atypical mycobacteria [14,15]. In a child who provides adequate sputum samples this may not be required. However, for the child with a suppressed cough, a diagnostic bronchoalveolar lavage may be of particular utility. Furthermore, the child with focal signs on physical examination or localized signs on chest imaging, may also benefit from a directed bronchoalveolar lavage [14,16,17]. The issue of sampling in BAL
http://dx.doi.org/10.1016/j.prrv.2016.05.005 1526-0542/ß 2016 Published by Elsevier Ltd.
Please cite this article in press as: Fitzgerald DA. Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis?. Paediatr. Respir. Rev. (2016), http://dx.doi.org/10.1016/j.prrv.2016.05.005
G Model
YPRRV-1134; No. of Pages 2 2
D.A. Fitzgerald / Paediatric Respiratory Reviews xxx (2016) xxx–xxx
has been previously addressed and in one study the concordance between two sites accessed [right middle lobe and lingula] for bacterial pathogens was about 75%, emphasizing the heterogeneity of CF lung disease [17]. With this in mind, one must always consider the more sites accessed and larger volumes of fluid washed will increase the risk of complications of the procedure [11]. Bronchoscopy should be undertaken or supervised by experienced hands as well as assisted by anaesthetists comfortable with the procedure [18]. The rates of adverse events following the bronchoalveolar lavage are common in CF infants as outlined by Wainwright et al. [19]. In this study they compared 170 subjects to age five years in the BAL directed therapy trial [12] at a median age of 27 months with 163 asymptomatic CF subjects at a median age of 10 months having a routine BAL and found that the major adverse event rate was high at 9% for a post-operative fever >38.5 deg C and was 3% for a period of oxygen desaturation <90% needing intervention during the procedure. Similarly, the minor adverse events were more common, with 41% of parents reporting an altered cough in their children and 12% of subjects having a low grade post-operative fever of <38.5 deg C.. In the clinical setting there are multiple other factors to consider. These begin with an explanation to families of the risks and benefits of the procedure in their child and their willingness for the procedure to be undertaken, the availability of anaesthetic time in the operating theatre and the optimal timing of the procedure in relation to the clinical setting. For example, in a persistently symptomatic young person with two negative sputum cultures in whom you may suspect pseudomonas aeruginosa, one would consider a bronchoalveolar lavage for culture. The important role of bronchoscopy in clinical research is evident. At a time of intense focus on early lung disease, with interventions to modify the clinical course, there is a need for comparative specimens to provide accurate information about the biomarkers of evolving lung disease in young children [20]. Biomarkers such as neutrophil elastase gathered from bronchoalveolar lavage specimens at the age of three months have been demonstrated to be predictive of the development of bronchiectasis on chest CT scan imaging at age three years [21]. Complementary roles of bronchoalveolar lavage and lung clearance index have been demonstrated in research studies of young children with CF [22]. The role of bronchoalveolar lavage findings in terms of neutrophil percentages and interleukin-8 concentration have complemented the clinical outcomes such FEV1 with the use of dornase alpha; where its anti-inflammatory properties have been described as attempts are made to better understand the pathophysiology of CF suppurative lung disease [23]. The diversity of the airway microbiome has come into focus and here the role of bronchoalveolar lavage has proven useful in highlighting the differences of the upper and lower airway: the greater diversity of organisms in the nose and throat as compared to the greater abundance of organisms in the lower airways [24]. This also serves a clinical purpose for distinguishing upper airway infection versus lower airway infection with pseudomonas- although the significance of this in the longer term with regard to the need for when to instigate intensive treatment has not reached consensus. Thus, as outlined by the European Cystic Fibrosis Clinical Trial Network Standardisation Committee, the research role of bronchoalveolar lavage remains central to studies that can help to ascertain the effectiveness of CF transmembrane regulators [CFTR] genetic modifiers, anti-inflammatory agents and antibiotics in infants and young children with CF in large centres with experience in this regard [11,18]. Similarly, the potential importance of longitudinal studies using bronchoalveolar lavage with various interventions remains as the alteration of biomarkers in the evolution of lung disease becomes clearer. There is no proven benefit for routine surveillance bronchoscopies in CF [11].
From a clinical viewpoint, the role of bronchoscopy and bronchoalveolar lavage remains clear with suspicions of airway anatomical abnormalities in young children, for children of any age who appear to have an unexplained clinical course and for patients following lung transplantation for which considerations of anastomotic compromise, infection and rejection remain paramount. Acknowledgement I would like to thank Associate Professor Hiran Selvadurai for his constructive review of the manuscript. References [1] Kosorok MR, Zeng L, West SHE, et al. Acceleration of lung disease in children with cystic fibrosis after pseudomonas acquisition. Pediatr Pulmonol 2001;32:277–87. [2] Kerem E, Viviani L, Zolin A, et al. Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS Patient Registry. European Respiratory Journal 2014;43:125–33. [3] Dijk FN, McKay KM, Barzi F, Gaskin KJ, Fitzgerald DA. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011. http://dx.doi.org/ 10.1136/archdischild-2011-300449 [4] Armstrong DS, Grimwood K, Carlin JB, et al. Lower Airway Inflammation in Infants and Young Children with Cystic Fibrosis. Am J Respir Crit Care Med 1997;156:1197–204. [5] Sly PD, Brennan S, Gangell C, deKlerk N, Murray C, Mott L, et al. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009;180:146–52. [6] Thia LP, Calder A, Stocks J, et al. Is Chest CT. useful in newborn screened infants with cystic fibrosis at 1 year of age? Thorax 2014;69:320–7. [7] Bush A, Sly PD. Evolution of cystic fibrosis lung function in the early years. Current Opinion in Pulmonary Medicine 2015;21:602–8. [8] Choo EM, Seaman JC, Musani AI. Tracheomalacia/tracheobronchomalacia and hyperdynamic airway collapse. Immunology and Allergy Clinics of North America 2013;33:23–34. [9] Fischer AJ, Singh SS, Adam RJ. et al Tracheomalacia is associated with lower FEV1 and Pseudomonas acquisition in children with CF. Ped Pulmonol 2014;49:960–70. [10] Kirkby S, Haynes Jr D. Pediatric lung transplantation: indications and outcomes. J Thorac Surg 2014;6:1024–31. [11] Fayon M, Kent L, Bui S, Dupont L, Sermet I. European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee. Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis. ERJ doi: 10.1183/09031936.00017713. [12] Wainwright CE, Vidmar S, Armstrong DS, et al. Effect of Bronchoalveolar Lavage-Directed Therapy on Pseudomonas aeruginosa Infection and Structural Lung Injury in Children with Cystic Fibrosis. A Randomized Trial. JAMA 2011;306:163–71. [13] Moodie M, Lal A, Vidmar S, et al. Costs of Bronchoalveolar lavage –directed therapy in the first five years of life for children with cystic fibrosis. J Pediatr 2014;165:564–9. [14] Gagliardo C, Saiman L. Microbiology of cystic fibrosis: Epidemiology of cystic fibrosis pathogens and clinical microbiology laboratory methods. Hodson and Geddes’ Cystic Fibrosis 2015;174. [15] Leung JM, Oliver KN. Nontuberculous mycobacteria in patients with cystic fibrosis. In Seminars in respiratory and critical care medicine 2013;34:124–34. [16] Gilchrist FJ, Salamat S, Clayton S, Peach J, Alexander J, Lenney W. Bronchoalveolar lavage in children: how many lobes should be sampled? Arch Dis Child 2011;96:215–7. [17] Gutierrez JP, Grimwood K, Armstrong DS, et al. Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis. Eur Respir J 2001;17:281–6. [18] Faro A, Wood RE, Schechter MS, Leong AB, Wittkugel E, Abode K, et al. Official American Thoracic Society technical standards: flexible airway endoscopy in children. Am J Respir Crit Care Med 2015;191:1066–80. [19] Wainwright CE, Grimwood K, Carlin JB, et al. Safety of bronchoalveolar lavage in young children with cystic fibrosis. Pediatr Pulmonol 2008;43:965–72. [20] Ramsey K, Schultz A, Stick SM. Biomarkers in Pediatric Cystic Fibrosis Lung Disease. Pediatr Respir Rev 2015. http://dx.doi.org/10.1016/j.prrv.2015.05.004. [21] Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, et al. Risk Factors for Bronchiectasis in Children with Cystic Fibrosis. N Eng J Med 2013;368:1963–70. [22] Belessis Y, Dixon B, Hawkins G, et al. Early Cystic Fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index. Am J Respir Crit Care Med 2012;185:862–73. [23] Paul K, Rietschel E, Ballmann M, et al. Effect of Treatment with Dornase Alpha on Airway Inflammation in Patients with Cystic Fibrosis. Am J Respir Crit Care Med 2004;169:719–25. [24] Boutin S, Graeber SY, Weitnauer M, et al. Comparison of Microbiomes from Different Niches of Upper and Lower Airways in Children and Adolescents with Cystic Fibrosis. PLOSONE/DOI:10.1371/journal.pone.0116029.
Please cite this article in press as: Fitzgerald DA. Cystic Fibrosis Frequently Asked Questions No 9: What is the role for bronchoscopy and bronchoalveolar lavage in Cystic Fibrosis?. Paediatr. Respir. Rev. (2016), http://dx.doi.org/10.1016/j.prrv.2016.05.005