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Jain K, Wainwright CE, Smyth AR. Bronchoscopy-guided antimicrobial therapy for cystic fibrosis. Cochrane Database Syst Rev 2024; 5:CD009530. [PMID: 38700027 PMCID: PMC11066959 DOI: 10.1002/14651858.cd009530.pub5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
BACKGROUND Early diagnosis and treatment of lower respiratory tract infections is the mainstay of management of lung disease in cystic fibrosis (CF). When sputum samples are unavailable, diagnosis relies mainly on cultures from oropharyngeal specimens; however, there are concerns about whether this approach is sensitive enough to identify lower respiratory organisms. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL) are invasive but allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may increase the accuracy of diagnosis of lower respiratory tract infections and improve the selection of antimicrobials, which may lead to clinical benefits. This is an update of a previous review that was first published in 2013 and was updated in 2016 and in 2018. OBJECTIVES To evaluate the use of bronchoscopy-guided (also known as bronchoscopy-directed) antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. The date of the most recent searches was 1 November 2023. SELECTION CRITERIA We included randomised controlled studies involving people of any age with CF that compared the outcomes of antimicrobial therapies guided by the results of bronchoscopy (and related procedures) versus those guided by any other type of sampling (e.g. cultures from sputum, throat swab and cough swab). DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information when required. We assessed the certainty of the evidence using the GRADE criteria. MAIN RESULTS We included two studies in this updated review. One study enrolled 170 infants under six months of age who had been diagnosed with CF through newborn screening. Participants were followed until they were five years old, and data were available for 157 children. The study compared outcomes for pulmonary exacerbations following treatment directed by BAL versus standard treatment based on clinical features and oropharyngeal cultures. The second study enrolled 30 children with CF aged between five and 18 years and randomised participants to receive treatment based on microbiological results of BAL triggered by an increase in lung clearance index (LCI) of at least one unit above baseline or to receive standard treatment based on microbiological results of oropharyngeal samples collected when participants were symptomatic. We judged both studies to have a low risk of bias across most domains, although the risk of bias for allocation concealment and selective reporting was unclear in the smaller study. In the larger study, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was low because Pseudomonas aeruginosa isolation in BAL samples at five years of age in both groups were much lower than the expected rate that was used for the power calculation. We graded the certainty of evidence for the key outcomes as low, other than for high-resolution computed tomography scoring and cost-of-care analysis, which we graded as moderate certainty. Both studies reported similar outcomes, but meta-analysis was not possible due to different ways of measuring the outcomes and different indications for the use of BAL. Whether antimicrobial therapy is directed by the use of BAL or standard care may make little or no difference in lung function z scores after two years (n = 29) as measured by the change from baseline in LCI and forced expiratory volume in one second (FEV1) (low-certainty evidence). At five years, the larger study found little or no difference between groups in absolute FEV1 z score or forced vital capacity (FVC) (low-certainty evidence). BAL-directed therapy probably makes little or no difference to any measure of chest scores assessed by computed tomography (CT) scan at either two or five years (different measures used in the two studies; moderate-certainty evidence). BAL-directed therapy may make little or no difference in nutritional parameters or in the number of positive isolates of P aeruginosa per participant per year, but may lead to more hospitalisations per year (1 study, 157 participants; low-certainty evidence). There is probably no difference in average cost of care per participant (either for hospitalisations or total costs) at five years between BAL-directed therapy and standard care (1 study, 157 participants; moderate-certainty evidence). We found no difference in health-related quality of life between BAL-directed therapy and standard care at either two or five years, and the larger study found no difference in the number of isolates of Pseudomonas aeruginosa per child per year. The eradication rate following one or two courses of eradication treatment and the number of pulmonary exacerbations were comparable in the two groups. Mild adverse events, when reported, were generally well tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of BAL in 4.8% of procedures. AUTHORS' CONCLUSIONS This review, limited to two well-designed randomised controlled studies, shows no evidence to support the routine use of BAL for the diagnosis and management of pulmonary infection in preschool children with CF compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence is available for adults.
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Affiliation(s)
- Kamini Jain
- Leicester Children's Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Claire E Wainwright
- Department of Respiratory Medicine, Royal Children's Hospital, Brisbane, Australia
| | - Alan R Smyth
- Division of Child Health, Obstetrics & Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
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Menditto VG, Mei F, Fabrizzi B, Bonifazi M. Role of bronchoscopy in critically ill patients managed in intermediate care units - indications and complications: A narrative review. World J Crit Care Med 2021; 10:334-344. [PMID: 34888159 PMCID: PMC8613715 DOI: 10.5492/wjccm.v10.i6.334] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/18/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Flexible bronchoscopy (FB) has become a standard of care for the triad of inspection, sampling, and treatment in critical care patients. It is an invaluable tool for diagnostic and therapeutic purposes in critically ill patients in intensive care unit (ICU). Less is known about its role outside the ICU, particularly in the intermediate care unit (IMCU), a specialized environment, where an intermediate grade of intensive care and monitoring between standard care unit and ICU is provided. In the IMCU, the leading indications for a diagnostic work-up are: To visualize airway system/obstructions, perform investigations to detect respiratory infections, and identify potential sources of hemoptysis. The main procedures for therapeutic purposes are secretion aspiration, mucus plug removal to solve atelectasis (total or lobar), and blood aspiration during hemoptysis. The decision to perform FB might depend on the balance between potential benefits and risks due to frailty of critically ill patients. Serious adverse events related to FB are relatively uncommon, but they may be due to lack of expertise or appropriate precautions. Finally, nowadays, during dramatic recent coronavirus disease 2019 (COVID-19) pandemic, the exact role of FB in COVID-19 patients admitted to IMCU has yet to be clearly defined. Hence, we provide a concise review on the role of FB in an IMCU setting, focusing on its indications, technical aspects and complications.
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Affiliation(s)
- Vincenzo G Menditto
- Department of Emergency Medicine, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona 60126, Italy
| | - Federico Mei
- Respiratory Diseases Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona 60126, Italy
| | - Benedetta Fabrizzi
- Cystic Fibrosis Regional Reference Center, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona 60126, Italy
| | - Martina Bonifazi
- Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Ancona 60126, Italy
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Pontefract BA, Ho HT, Crain A, Kharel MK, Nybo SE. Drugs for Gram-Negative Bugs From 2010-2019: A Decade in Review. Open Forum Infect Dis 2020; 7:ofaa276. [PMID: 32760748 PMCID: PMC7393798 DOI: 10.1093/ofid/ofaa276] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 06/24/2020] [Indexed: 11/14/2022] Open
Abstract
A literature review spanning January 1, 2010, to December 31, 2019, was conducted using the PubMed and ISI Web of Science databases to determine the breadth of publication activity in the area of gram-negative bacteria antimicrobial therapy. The number of articles was used as a reflection of scholarly activity. First, PubMed was searched using the following Medical Subject Headings (MeSH): antibacterial agents, Enterobacteriaceae, Acinetobacter, and Pseudomonas. A total of 12 643 articles were identified within PubMed, and 77 862 articles were identified within ISI Web of Science that included these terms. Second, these articles were categorized by antibiotic class to identify relative contributions to the literature by drug category. Third, these studies were used to identify key trends in the treatment of gram-negative bacterial infections from the past decade. This review highlights advances made in the past 10 years in antibacterial pharmacotherapy and some of the challenges that await the next decade of practice.
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Affiliation(s)
| | - Hong T Ho
- Ferris State University, College of Pharmacy, Big Rapids, Michigan, USA
| | - Alexandria Crain
- Ferris State University, College of Pharmacy, Big Rapids, Michigan, USA
| | - Madan K Kharel
- University of Maryland Eastern Shore, Department of Pharmaceutical Sciences, Princess Anne, Maryland, USA
| | - S Eric Nybo
- Ferris State University, College of Pharmacy, Big Rapids, Michigan, USA
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Taccetti G, Denton M, Hayes K, Drevinek P, Sermet-Gaudelus I, Bilton D, Campana S, Dolce D, Ferroni A, Héry-Arnaud G, Martin-Gomez MT, Nash E, Pereira L, Pressler T, Tümmler B. A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials. J Cyst Fibros 2020; 19:52-67. [DOI: 10.1016/j.jcf.2019.08.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 07/23/2019] [Accepted: 08/15/2019] [Indexed: 01/23/2023]
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Detecting respiratory infection in children with cystic fibrosis: Cough swab, sputum induction or bronchoalveolar lavage. Paediatr Respir Rev 2019; 31:28-31. [PMID: 31153794 DOI: 10.1016/j.prrv.2019.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 03/05/2019] [Indexed: 11/21/2022]
Abstract
Young children with cystic fibrosis (CF) are generally very well, cough free and non-productive, and are often incapable of spontaneously expectorating sputum even if actively coughing during an exacerbation. Obtaining a meaningful airway sample for microbiological analysis is therefore problematic, yet essential if lower airway infection is to be detected and adequately treated. Recently there has been increasing interest in the use of sputum-induction in young children with CF, as a simple, cost effective, well tolerated and frequently repeatable approach to sampling the lower airway, and the relative merits of this approach to bacterial sampling are discussed. Culture-independent microbiology has increased our understanding of the respiratory microbiota and has challenged the current paradigm of "single pathogen causes disease". Understanding how to diagnose infection using these new, highly sensitive technologies will be important. How we should best intervene to optimise, manipulate and prevent disruption of the respiratory microbiota is likely to greatly influence how we manage infection in the future.
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Abstract
BACKGROUND Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organisms.Bronchoscopy and related procedures (including bronchoalveolar lavage) though invasive, allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may help in a more accurate diagnosis of lower respiratory tract infections and guide the selection of antimicrobials, which may lead to clinical benefits.This is an update of a previous review. OBJECTIVES To evaluate the use of bronchoscopy-guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 30 August 2018.We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. Date of latest search: 10 April 2018. SELECTION CRITERIA We included randomized controlled studies including people of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (and related procedures) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab). DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS The search identified 11 studies, but we only included one study enrolling infants with cystic fibrosis under six months of age and diagnosed through newborn screening (170 enrolled); participants were followed until they were five years old (data from 157 children). The study compared outcomes following therapy directed by bronchoalveolar lavage for pulmonary exacerbations with standard treatment based on clinical features and oropharyngeal cultures.We considered this study to have a low risk of bias; however, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was limited due to the prevalence (of Pseudomonas aeruginosa isolation in bronchoalveolar lavage samples at five years age) being much lower in both the groups compared to that which was expected and which was used for the power calculation. The sample size was adequate to detect a difference in high-resolution computed tomography scoring. The quality of evidence for the key parameters was graded as low except high-resolution computed tomography scoring and cost of care analysis, which were graded as moderate quality.At five years of age, there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters. Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups.In addition, this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the standard therapy group. The eradication rate following one or two courses of eradication treatment was comparable in the two groups, as were the number of pulmonary exacerbations. However, the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group, but the mean duration of hospitalizations was significantly less compared to the standard therapy group.Mild adverse events were reported in a proportion of participants, but these were generally well-tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of bronchoalveolar lavage in 4.8% of procedures. AUTHORS' CONCLUSIONS This review, limited to a single, well-designed randomized controlled study, shows no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence was available for adult and adolescent populations.
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Affiliation(s)
- Kamini Jain
- University of NottinghamDivision of Child Health, School of Clinical SciencesE Floor, East Block, Queen's Medical CentreDerby RoadNottinghamUKNG9 2SJ
| | - Claire Wainwright
- Royal Children's HospitalDepartment of Respiratory MedicineHerston RoadHerstonBrisbaneQueenslandAustralia4029
| | - Alan R Smyth
- School of Medicine, University of NottinghamDivision of Child Health, Obstetrics & Gynaecology (COG)Queens Medical CentreDerby RoadNottinghamUKNG7 2UH
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Chen T, Qiu L, Zhong L, Tao Q, Liu H, Chen L. Flexible bronchoscopy in pulmonary diseases in children with congenital cardiovascular abnormalities. Exp Ther Med 2018; 15:5481-5486. [PMID: 29904428 DOI: 10.3892/etm.2018.6113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 03/05/2018] [Indexed: 11/06/2022] Open
Abstract
There is a lack of data describing the role of flexible bronchoscopy (FB) in evaluating pulmonary diseases in children with congenital cardiovascular abnormalities in China. Determining whether those children suffer from respiratory complications may be useful for future preoperative planning and family counseling. The present study aimed to investigate the features and FB-associated findings with respect to pulmonary diseases in children with congenital cardiovascular abnormalities. The role of FB in guiding the treatment and safety of procedures was also evaluated. A cohort of 57 children with congenital cardiovascular abnormalities underwent FB for pulmonary diseases between November 2013 and June 2015. The demographics, bronchoscopy diagnoses, cellular analysis and microbiology of bronchoalveolar lavage fluid (BALF), and the clinically valuable contributions and side-effects of FB were analyzed retrospectively. The bronchoscopies were performed in patients with a median age of 4 months (range, 9 days-9 years) and 9 patients were intubated and mechanically ventilated. The most common types of congenital cardiovascular abnormalities were atrial septal defect, ventricular septal defect and patent ductus arteriosus. External compression of airways, tracheobronchomalacia, laryngomalacia, and airway narrowing were the most common airway abnormalities revealed by FB. BALF cellular analysis revealed an elevated total cell count and neutrophil percentage; 19.2% specimens harbored an etiological agent. FB findings contributed towards the clinical management of 26.3% patients. The complications of FB were mild and transient. In the present study, the majority of patients with cardiovascular abnormalities exhibited other airway disorders. The present findings suggest that FB was a useful and safe tool in the evaluation of this specific group of children.
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Affiliation(s)
- Ting Chen
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Li Qiu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Lin Zhong
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Qingfen Tao
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Hanmin Liu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Lina Chen
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial. THE LANCET RESPIRATORY MEDICINE 2018; 6:461-471. [PMID: 29778403 PMCID: PMC5971213 DOI: 10.1016/s2213-2600(18)30171-1] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 04/02/2018] [Accepted: 04/10/2018] [Indexed: 01/10/2023]
Abstract
Background Pathogen surveillance is challenging but crucial in children with cystic fibrosis—who are often non-productive of sputum even if actively coughing—because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage. Methods This prospective internally controlled interventional trial was done at the Children's Hospital for Wales (Cardiff, UK) in children with cystic fibrosis aged between 6 months and 18 years. Samples from cough swab, sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage were matched for within-patient comparisons. Primary outcomes were comparative pathogen yield between sputum induction and cough swab for stage 1, and between sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage for stage 2. Data were analysed as per protocol. This study is registered with the UK Clinical Research Network (14615) and with the International Standard Randomised Controlled Trial Network Registry (12473810). Findings Between Jan 23, 2012, and July 4, 2017, 124 patients were prospectively recruited to the trial and had 200 sputum induction procedures for stage 1. 167 (84%) procedures were successful and the procedure was well tolerated. Of the 167 paired samples, 63 (38%) sputum-induction samples were pathogen positive compared with 24 (14%) cough swabs (p<0·0001; odds ratio [OR] 7·5; 95% CI 3·19–17·98). More pathogens were isolated from sputum induction than cough swab (79 [92%] of 86 vs 27 [31%] of 86; p<0·0001). For stage 2, 35 patients had a total of 41 paired sputum-induction and bronchoalveolar lavage procedures. Of the 41 paired samples, 28 (68%) were positive for at least one of the concurrent samples. 39 pathogens were isolated. Sputum induction identified 27 (69%) of the 39 pathogens, compared with 22 (56%; p=0·092; OR 3·3, 95% CI 0·91–12·11) on single-lobe, 28 (72%; p=1·0; OR 1·1, 95% CI 0·41–3·15) on two-lobe, and 33 (85%; p=0·21; OR 2·2, 95% CI 0·76–6·33) on six-lobe bronchoalveolar lavage. Interpretation Sputum induction is superior to cough swab for pathogen detection, is effective at sampling the lower airway, and is a credible surrogate for bronchoalveolar lavage in symptomatic children. A substantial number of bronchoscopies could be avoided if sputum induction is done first and pathogens are appropriately treated. Both sputum induction and six-lobe bronchoalveolar lavage provide independent, sizeable gains in pathogen detection compared with the current gold-standard two-lobe bronchoalveolar lavage. We propose that sputum induction and six-lobe bronchoalveolar lavage combined are used as standard of care for comprehensive lower airway pathogen detection in children with cystic fibrosis. Funding Health and Care Research Wales—Academic Health Science Collaboration and Wellcome Trust Institutional Strategic Support Fund.
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Zemanick ET, Wagner BD, Robertson CE, Ahrens RC, Chmiel JF, Clancy JP, Gibson RL, Harris WT, Kurland G, Laguna TA, McColley SA, McCoy K, Retsch-Bogart G, Sobush KT, Zeitlin PL, Stevens MJ, Accurso FJ, Sagel SD, Harris JK. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J 2017; 50:50/5/1700832. [PMID: 29146601 DOI: 10.1183/13993003.00832-2017] [Citation(s) in RCA: 164] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/10/2017] [Indexed: 01/20/2023]
Abstract
Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status.BALF from paediatric and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing.We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2 years, nontraditional taxa (e.gStreptococcus, Prevotella and Veillonella) constituted ∼50% of the microbiota, whereas in CF patients aged ≥6 years, traditional CF taxa (e.gPseudomonas, Staphylococcus and Stenotrophomonas) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (e.gStreptococcus or Prevotella) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of Streptococcus, Prevotella and Veillonella were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF.The CF microbiota detected in BALF differs with age. In CF patients aged <2 years, Streptococcus predominates, whereas classic CF pathogens predominate in most older children and adults.
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Affiliation(s)
| | - Brandie D Wagner
- University of Colorado School of Medicine, Aurora, CO, USA.,Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | | | | | - James F Chmiel
- Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, USA
| | - John P Clancy
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ronald L Gibson
- University of Washington, Seattle Children's Hospital, Seattle, WA, USA
| | | | | | | | - Susanna A McColley
- Ann and Robert H. Lurie Children's Hospital of Chicago and Northwestern University, Chicago, IL, USA
| | - Karen McCoy
- Nationwide Children's Hospital, Columbus, OH, USA
| | | | | | | | - Mark J Stevens
- University of Colorado School of Medicine, Aurora, CO, USA
| | | | - Scott D Sagel
- University of Colorado School of Medicine, Aurora, CO, USA
| | - J Kirk Harris
- University of Colorado School of Medicine, Aurora, CO, USA
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Paul L. Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in cystic fibrosis and its clinical use. J Thorac Dis 2017; 9:S1139-S1145. [PMID: 29214071 DOI: 10.21037/jtd.2017.06.143] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases. Though bronchoscopy has been used in conjunction with other modalities such as computed tomography and sputum induction providing a better understanding of the progression of the disease, it still remains valuable in the diagnosis and management of CF.
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Affiliation(s)
- Lisa Paul
- Division of Pulmonary, Critical Care and Sleep, Westchester Medical Center and New York Medical College of Touro, Valhalla, NY, USA.,Adult Cystic fibrosis Center, Valhalla, NY, USA
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11
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Abstract
For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.
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Affiliation(s)
- Marijke Proesmans
- Department of Paediatrics, UZ Leuven, Herestraat 49,
3000 Leuven, Belgium
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12
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Stehling F, Pieper N, Bouikidis A, Steinmann J, Rath PM, Mellies U. Upper airway microbial colonization in patients with neuromuscular disorders. Respirology 2016; 21:1285-91. [DOI: 10.1111/resp.12814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Revised: 02/03/2016] [Accepted: 02/27/2016] [Indexed: 11/28/2022]
Affiliation(s)
- Florian Stehling
- Pediatric Pulmonology and Sleep Medicine; University of Duisburg-Essen Children's Hospital; Essen Germany
| | - Nadine Pieper
- Pediatric Pulmonology and Sleep Medicine; University of Duisburg-Essen Children's Hospital; Essen Germany
| | - Anastasios Bouikidis
- Pediatric Pulmonology and Sleep Medicine; University of Duisburg-Essen Children's Hospital; Essen Germany
| | - Joerg Steinmann
- Institute of Medical Microbiology; University Hospital Essen, University of Duisburg-Essen; Essen Germany
| | - Peter-Michael Rath
- Institute of Medical Microbiology; University Hospital Essen, University of Duisburg-Essen; Essen Germany
| | - Uwe Mellies
- Pediatric Pulmonology and Sleep Medicine; University of Duisburg-Essen Children's Hospital; Essen Germany
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13
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Abstract
BACKGROUND Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organisms.Bronchoscopy and related procedures (including bronchoalveolar lavage) though invasive, allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may help in a more accurate diagnosis of lower respiratory tract infections and guide the selection of antimicrobials, which may lead to clinical benefits.This is an update of a previous review. OBJECTIVES To evaluate the use of bronchoscopy-guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched two registries of ongoing studies and the reference lists of relevant articles and reviews.Date of latest search: 28 August 2015. SELECTION CRITERIA We included randomized controlled studies including people of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (and related procedures) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab). DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information. MAIN RESULTS The search identified nine studies, but only one study with data from 157 participants (170 people were enrolled) was eligible for inclusion in the review. This study compared outcomes following therapy directed by bronchoalveolar lavage for pulmonary exacerbations during the first five years of life with standard treatment based on clinical features and oropharyngeal cultures. The study enrolled infants with CF who were under six months of age and diagnosed through newborn screening and followed them until they were five years old.We considered this study to have a low risk of bias; however, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was limited due to the prevalence (of Pseudomonas aeruginosa isolation in bronchoalveolar lavage samples at five years age) being much lower in both the groups compared to that which was expected and which was used for the power calculation. The sample size was adequate to detect a difference in high-resolution computed tomography scoring. The quality of evidence for the key parameters was graded as moderate except high-resolution computed tomography scoring and cost of care analysis, which were graded as high quality.At five years of age, there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters. Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups.In addition, this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the standard therapy group. The eradication rate following one or two courses of eradication treatment was comparable in the two groups, as were the number of pulmonary exacerbations. However, the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group, but the mean duration of hospitalizations was significantly less compared to the standard therapy group.Mild adverse events were reported in a proportion of participants, but these were generally well-tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of bronchoalveolar lavage in 4.8% of procedures. AUTHORS' CONCLUSIONS This review, limited to a single, well designed randomized-controlled study, shows no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence was available for adult and adolescent populations.
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Affiliation(s)
- Kamini Jain
- Division of Child Health, School of Clinical Sciences, University of Nottingham, E Floor, East Block, Queen's Medical Centre, Derby Road, Nottingham, UK, NG9 2SJ
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