Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

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.

Antibiotics for chronic pulmonary infection in children with a neurodisability (neurodevelopmental disorder).

BACKGROUND: 'Neurodisability' refers to a group of conditions that result primarily from a neurological problem (e.g. cerebral palsy), neuromuscular problem (e.g. a muscular dystrophy) or developmental problems (e.g. developmental impairment, Down syndrome). Children and young people with these conditions may have similar problems with mobility, feeding and airway clearance. Chest and breathing problems (including pulmonary infections) are commonly experienced by children and young people with neurodisabilities and are often a cause for them requiring hospital care. For those who are unable to completely clear their airway of secretions, or have frequent infections, pulmonary infections may not be able to be completely eradicated and therefore become chronic. It is unclear what treatment is best for children and young people in this position. OBJECTIVES: To assess the effectiveness and adverse effects of antibiotic treatment for chronic pulmonary infection in children and young people living with a neurodisability, including quality-of-life measures, effects on hospitalisation and healthcare contacts. SEARCH METHODS: We searched the Cochrane Airways Trials Register, Cochrane Acute Respiratory Infections Group Register of Trials (CARIGRT), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), OpenGrey (www.opengrey.eu) and three trials registries up to 8 February 2022. Additionally, we identified related systematic reviews through Epistemonikos.org (8 February 2022) and searched reference lists of these. SELECTION CRITERIA: All randomised controlled trials of antibiotic therapy for chronic pulmonary infection in children and young people up to the age of 18 living with a neurodisability were eligible. DATA COLLECTION AND ANALYSIS: Two independent review authors screened results of the searches against predetermined inclusion criteria, resolving any discrepancies by discussion. MAIN RESULTS: We identified a total of 1968 independent records through our searches, of which we assessed six full-text articles for eligibility. We identified one ongoing study as well as one related substudy but did not identify any completed studies eligible for inclusion in this systematic review. AUTHORS' CONCLUSIONS: The findings of this systematic review highlight a lack of evidence in the antibiotic treatment of chronic pulmonary infection in children and young people up to the age of 18 living with a neurodisability. Further research examining this topic is therefore required.

Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

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.

Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

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.

Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.

BACKGROUND: Early diagnosis and treatment of lower respiratory tract infections, particularly those with Pseudomonas aeruginosa, 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. 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 November 2013. SELECTION CRITERIA: We included randomized controlled studies including patients of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (including bronchoalveolar lavage or protected bronchial brush sampling) 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 patients 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 for high-resolution computed tomography scoring, which was graded as high.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 patients, 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, which only includes a single study, shows that there is 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.

Current dilemmas in antimicrobial therapy in cystic fibrosis.

The majority of cystic fibrosis (CF)-related morbidity and mortality is caused by pulmonary damage due to recurrent and chronic infections. Considerable improvements in the survival of individuals with CF have been achieved in recent decades, some of which may be due to better management of common pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. While the search continues for the optimal approach for prophylaxis, eradication and maintenance treatment of infections, there are several unanswered questions, posing dilemmas related to various therapeutic choices. Microbes pose additional challenges by adapting to CF lungs and developing treatment resistance. Several new, highly antimicrobial-resistant pathogens have emerged. Their pathogenic role in the progression of CF lung disease is not yet clear and effective treatment approaches have not been defined. There is an urgent need for well-designed comparative clinical trials of new antibiotic strategies.

Influence of seasonal temperature on the repeat swimming performance of rainbow trout Oncorhynchus mykiss.

While the temperature dependence of exercise performance in fishes is reasonably well documented, information on the temperature dependence of metabolic recovery and reperformance is scant. This study examined the recovery of swimming performance after exhaustive exercise in rainbow trout Oncorhynchus mykiss at seasonal temperatures ranging from 5 to 17 degrees C and explored the relationship between performance and preceding metabolic state. The primary objective of the study was to test the hypothesis that increased temperature increases the capability of rainbow trout to repeat a critical swimming speed (U(crit)), as assessed by two consecutive critical swimming speed tests separated by a 40 min rest interval. An additional expectation was that certain plasma ionic, metabolic and humoral parameters would be correlated with how well fish reperformed and so plasma levels of lactate, potassium, ammonia, osmolality, sodium and cortisol, as well as hematocrit, were monitored before, during and after the swim challenges via an indwelling cannula in the dorsal aorta. As expected, performance in the first U(crit) test (U(crit1)) was positively related to temperature. However, the relationship between U(crit1) and reperformance (U(crit2)) was not dependent on acclimation temperature in a simple manner. Contrary to our expectations, U(crit2) was less than U(crit1) for warm-acclimated fish (14.9+/-1.0 degrees C), whereas U(crit2) equaled U(crit1) for cold-acclimated fish (8.4+/-0.9 degrees C). Cold-acclimated fish also exhibited a lower U(crit1) and less metabolic disruption compared with warm-acclimated fish. Thus, while warm acclimation conferred a faster U(crit1), a similar swimming speed could not be attained on subsequent swim after a 40 min recovery period. This finding does not support the hypothesis that the ability of rainbow trout to reperform on U(crit) test is improved with temperature. Both plasma lactate and plasma potassium levels were strongly correlated with U(crit1) performance. Therefore, the higher U(crit1) of warm-acclimated fish may have been due in part to a greater anaerobic swimming effort compared with cold-acclimated fish. In fact, a significant correlation existed between the plasma lactate concentration prior to the start of the second test and the subsequent U(crit2) performance, such that U(crit2) decreased when a threshold plasma lactate level of around 12.2 mmol l(-1) was surpassed for the initial swim. No other measured plasma variable showed a significant relationship with the U(crit2) performance. We conclude that warm-acclimated fish, by apparently swimming harder and possibly more anaerobically compared with cold-acclimated fish, were unable to recovery sufficiently well during the fixed recovery period to repeat this initial level of performance, and this poorer repeat performance was correlated with elevations in plasma lactate levels.