Management Of Pulmonary Exacerbations Research Articles

Experiences Among Patients With Cystic Fibrosis in the MucoExocet Study of Using Connected Devices for the Management of Pulmonary Exacerbations: Grounded Theory Qualitative Research.

Early detection of pulmonary exacerbations (PEx) in patients with cystic fibrosis is important to quickly trigger treatment and reduce respiratory damage. An intervention was designed in the frame of the MucoExocet research study providing patients with cystic fibrosis with connected devices and educating them to detect and react to their early signs of PEx. This study aims to identify the contributions and conditions of home monitoring in relation to their care teams from the users' point of view to detect PEx early and treat it. This study focused on the patients' experiences as the first and main users of home monitoring. A qualitative study was conducted to explore patients' and professionals' experiences with the intervention. We interviewed patients who completed the 2-year study using semistructured guides and conducted focus groups with the care teams. All the interviews were recorded and transcribed verbatim. Their educational material was collected. A grounded analysis was conducted by 2 researchers. A total of 20 patients completed the study. Three main categories emerged from the patients' verbatim transcripts and were also found in those of the professionals: (1) task technology fit, reflecting reliability, ease of use, accuracy of data, and support of the technology; (2) patient empowerment through technology, grouping patients' learnings, validation of their perception of exacerbation, assessment of treatment efficacy, awareness of healthy behaviors, and ability to react to PEx signs in relation to their care team; (3) use, reflecting a continuous or intermittent use, the perceived usefulness balanced with cumbersome measurements, routinization and personalization of the measurement process, and the way data are shared with the care team. Furthermore, 3 relationships were highlighted between the categories that reflect the necessary conditions for patient empowerment through the use of technology. We discuss a theorization of the process of patient empowerment through the use of connected devices and call for further research to verify or amend it in the context of other technologies, illnesses, and care organizations. ClinicalTrials.gov NCT03304028; https://clinicaltrials.gov/ct2/show/results/NCT03304028.

717 Provider practices in management of pulmonary exacerbations in the era of highly effective modulator therapy

717 Provider practices in management of pulmonary exacerbations in the era of highly effective modulator therapy

A scoping review of clinical pharmacist and pharmacy technician contributions to cystic fibrosis care

AbstractThe purpose of this scoping literature review was to assess available published literature/abstracts, and to examine described contributions by pharmacists and/or pharmacy technicians as part of the care of people with cystic fibrosis (pwCF). This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for Scoping Reviews (PRISMA‐ScR). Published abstracts and articles from inception through December 2022 were included if they described care of pwCF (all ages), with at least one group of participants receiving care/services from pharmacy staff, and were available in English. Data extractions were outcomes, study, and participant characteristics. From 756 abstracts and papers, 91 were included. The majority were published abstracts (n = 67), from the United States (n = 64), retrospective cohort study design (n = 47), involved pharmacist intervention (n = 75), with no comparison group (n = 48), and in an outpatient/ambulatory setting (n = 59). Most often, literature were descriptions of specific pharmacist services, evaluations of adding a pharmacist, or descriptions of overall pharmacist practice/role. Specific pharmacist services were defined as patient or caregiver education, adherence support, medication reconciliation, management of pulmonary exacerbations, and medication management (including monitoring, and telehealth). Pharmacists and pharmacy technicians have contributed to the care of pwCF in various ways; however, much of the available data are currently disseminated in the form of conference abstracts. Efforts to support author publication of data as full peer‐reviewed publications should be prioritized as this data can help support others’ efforts to develop or support similar clinical pharmacy services.

Breath of fresh insight: unraveling the evolution of our understanding of cystic fibrosis pulmonary exacerbations.

Pulmonary exacerbations are critical events with significant negative impacts in persons with cystic fibrosis, but their diagnosis and management are highly variable. Highly effective modulator therapies have greatly improved health and reduced exacerbation events, but have also reshaped how they present. This review discusses the complexities of the diagnosis and management of pulmonary exacerbations as well as the emerging work and evidence in this area. The shifting epidemiology and our understanding of risk factors for pulmonary exacerbations are discussed. As symptoms may be more subtle in the modulator context, novel technologies including studies of remote monitoring are presented. The continued relevance of pulmonary exacerbations, the heterogeneity in their management, as well as current and forthcoming clinical trials to optimize treatment approaches are detailed. In spite of the dramatic reductions in pulmonary exacerbations, airway infections persist, a proportion of persons with cystic fibrosis either on or off modulator therapies continue to experience exacerbation events, and long-term data is lacking. Innovative approaches and studies will be crucial to enable standardized and generalizable strategies to improve outcomes in persons with cystic fibrosis.

BEAT CF pulmonary exacerbations core protocol for evaluating the management of pulmonary exacerbations in people with cystic fibrosis

BackgroundCystic fibrosis (CF) is a rare, inherited, life-limiting condition predominantly affecting the lungs, for which there is no cure. The disease is characterized by recurrent pulmonary exacerbations (PEx), which are thought to drive progressive lung damage. Management of these episodes is complex and generally involves multiple interventions targeting different aspects of disease. The emergence of innovative trials and use of Bayesian statistical methods has created renewed opportunities for studying heterogeneous populations in rare diseases. Here, we present the protocol for the BEAT CF PEx cohort, a prospective, multi-site, perpetual, platform enrolling adults and children with CF. The BEAT CF PEx cohort will be used to evaluate the comparative effectiveness of interventions for the treatment of PEx requiring intensive therapy (PERITs), with a primary focus on short-term improvements in lung function. This will be achieved through the conduct of cohort-nested studies, including adaptive clinical trials, within the BEAT CF PEx cohort. This protocol will outline key features of the BEAT CF PEx cohort, including the design, implementation, data collection and management, governance and analysis, and dissemination of results.MethodsThis platform will be conducted across multiple sites, commencing with CF treatment centers in Australia. People of all ages with a clinical diagnosis of CF will be eligible to participate, except those who have previously received a lung transplant. Data including demographic and clinical information, treatment details, and outcomes (including safety, microbiology, and patient-reported outcome measures including quality of life scores) will be systematically collected and securely stored via a digital centralized trial management system (CTMS). The primary endpoint is the absolute change in the percentage predicted forced expiratory volume in 1 s (ppFEV1) from the commencement of intensive therapy to 7 to 10 days afterwards.DiscussionThe BEAT CF PEx cohort will report clinical, treatment, and outcome data for PEx among people with CF and is intended to serve as a core (master) protocol for future nested, interventional trials evaluating treatment(s) for these episodes. The protocols for nested sub-studies are beyond the scope of this document and will be reported separately.Trial registrationANZCTR BEAT CF Platform – ACTRN12621000638831. Registration date: Sept. 26, 2022.

246 Provider practices in the management of pulmonary exacerbations in the era of highly effective modulator therapy

246 Provider practices in the management of pulmonary exacerbations in the era of highly effective modulator therapy

Antimicrobial Stewardship in Cystic Fibrosis.

The chronic airway infection and inflammation characteristic of cystic fibrosis (CF) ultimately leads to progressive lung disease, the primary cause of death in persons with CF (pwCF). Despite many recent advances in CF clinical care, efforts to preserve lung function in many pwCF still necessitate frequent antimicrobial use. Incorporating antimicrobial stewardship (AMS) principles into management of pulmonary exacerbations (PEx) would facilitate development of best practices for antimicrobial utilization at CF care centers. However, AMS can be challenging in CF given the unique aspects of chronic, polymicrobial infection in the CF airways, lack of evidence-based guidelines for managing PEx, limited utility for antimicrobial susceptibility testing, and increased frequency of adverse drug events in pwCF. This article describes current evidence-based antimicrobial treatment strategies for pwCF, highlights the potential for AMS to beneficially impact CF care, and provides practical strategies for integrating AMS programs into the management of PEx in pwCF.

Management of pregnancy in cystic fibrosis

To describe considerations for optimisation of preconception health.To describe the management of chronic CF therapies including CFTR modulators during pregnancy and lactation.To describe treatment of an acute pulmonary exacerbation during pregnancy.To describe the management of pregnancy in individuals with CF following organ transplantation.

Evaluating FEV1 decline in diagnosis and management of pulmonary exacerbations in children with cystic fibrosis.

RationaleForced expiratory volume in 1 s (FEV1) decline (ΔFEV1) is associated with pulmonary exacerbation (PEx) diagnosis in cystic fibrosis (CF). Spirometry may not be available during telehealth visits and could impair clinician ability to diagnose PEx. This study aims to (1) identify the associations between degrees of ΔFEV1 (decrease of <5% predicted vs. 5%−9% predicted vs. ≥10% predicted from baseline), clinical symptoms, and clinician‐diagnosed PEx and (2) evaluate the correlation between respiratory symptoms, ΔFEV1, and antibiotic treatment.MethodsRetrospective, descriptive study of PEx diagnosis and management in 628 outpatient clinical encounters with spirometry in 178 patients with CF ages 6−17 years at Riley Hospital for Children during 2019. Odds ratios (OR) of symptoms associated with clinician‐defined PEx diagnosis and antibiotic management stratified by ΔFEV1 decline were determined.ResultsClinician‐diagnosed PEx occurred at 199 (31.7%) visits; increased cough (77.4%) and sputum/wet cough (57.8%) were the most frequently reported symptoms. Compared to no ΔFEV1, the odds of a clinician‐diagnosed PEx were increased when ΔFEV15%−9% and ΔFEV1≥10% was present with increased cough (OR 1.56, 95% confidence interval [CI] 1.25−1.94 and OR 1.82, 95% CI 1.52−2.19, respectively), increased sputum (OR 1.59, 95% CI 1.20−2.12 and OR 1.78, 95% CI 1.37−2.32, respectively), and increased cough and sputum together (OR 1.51, 95% CI 1.08−2.13 and OR 1.68, 95% CI 1.22−2.31, respectively).ConclusionsΔFEV1 is associated with increased likelihood that cough and sputum are diagnosed as a PEx. Spirometry is essential for PEx diagnosis and treatment and is a necessary component of all clinical encounters.

Use of Dynamic Chest Radiography to Assess Treatment of Pulmonary Exacerbations in Cystic Fibrosis.

Background Although spirometry is an important marker in the management of pulmonary exacerbations in cystic fibrosis (CF), it is a forced maneuver and can generate aerosol. Therefore, it may be difficult to perform in some individuals. Dynamic chest radiography (DCR) provides real-time information regarding pulmonary dynamics alongside fluoroscopic-style thoracic imaging. Purpose To assess the effect of pulmonary exacerbation treatment by using both spirometry and DCR and assess the clinical utility of DCR in participants with CF experiencing pulmonary exacerbations. Materials and Methods In this prospective, observational, single-center pilot study, spirometry and DCR were performed before and after treatment of pulmonary exacerbations in participants with CF between December 2019 and August 2020. Spirometry measured forced expiratory volume in 1 second (FEV1) and forced vital capacity. DCR helped to measure projected lung area (PLA), hemidiaphragm midpoint position, and speed during tidal and deep breathing. Data were analyzed by using the paired t test or Wilcoxon signed-rank test. Correlation was assessed by using the Spearman rank correlation coefficient. Results Twenty participants with CF (mean age, 25 years ± 7 [standard deviation]; 14 women) were evaluated. Spirometry showed that percentage predicted FEV1 improved from a median of 44% (interquartile range [IQR], 17%) before treatment to 55% (IQR, 16%) after treatment (P = .004). DCR showed improvement in median deep breathing excursion for left and right hemidiaphragms (from 18 [IQR, 11] to 25 [IQR, 16] mm [P = .03] and from 13 [IQR, 6] to 19 [IQR, 14] mm [P = .03], respectively) and in median expiratory speed following deep breathing for left and right hemidiaphragms (from 7 [IQR, 2] to 11 [IQR, 5] mm/sec [P = .004] and 6 [IQR, 3] to 9 [IQR, 6] mm/sec [P = .004], respectively). PLA rate of change during full expiration and change in PLA during tidal breathing improved (from a mean of 42 cm2/sec ± 16 to 56 cm2/sec ± 24 [P = .03] and from a mean of 29 cm2 ± 14 to 35 cm2 ± 10 [P = .03], respectively). Conclusion Dynamic chest radiography demonstrated improvement in diaphragm speed and range of chest wall movement during respiration aftere treatment for pulmonary exacerbations in cystic fibrosis and showed potential as a tool to investigate the effect of pulmonary exacerbations on lung mechanics. Clinical trials registration no. NCT01234567 Published under a CC BY 4.0 license. Online supplemental material is available for this article.

176: Evaluating use of FEV1 decline in diagnosis and management of pulmonary exacerbations in children with cystic fibrosis

176: Evaluating use of FEV1 decline in diagnosis and management of pulmonary exacerbations in children with cystic fibrosis

Does Cefiderocol Have a Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management?

Cystic fibrosis (CF) is associated with frequent pulmonary exacerbations and the need for novel antibiotics against antimicrobial resistance. Cefiderocol is a newly approved therapeutic option active against a variety of multidrug resistant (MDR) bacteria such as gram-negative species commonly encountered by CF patients. This review describes the potential role of cefiderocol against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cepacia complex. Cefiderocol is a potential therapeutic option for MDR pathogens with minimum inhibitory concentrations (MICs) of ≤4 mg/L. Due to the lack of in vivo evidence in the CF population, cefiderocol may be utilized in patients in which alternative options are lacking due to MDR organisms or rapid pulmonary decline.

Allergic-like disorders and asthma in patients with common variable immunodeficiency: a multi-center experience

Objective Common variable immune deficiency (CVID) encompasses a variety of diseases characterized by disturbed immunoglobulin (Ig) production and various immune dysregulations. Scarce data are available regarding relationships between CVID and allergic diseases. Here we examined possible associations between allergies and CVID. Methods For this multicenter study, we prospectively enrolled 79 adult CVID patients (≥18 years) who were diagnosed and treated between 2002–2017 at the Hadassah-Hebrew University and Shaare Zedek Medical Centers, Jerusalem, Israel. These patients were examined for allergic manifestations. Patient evaluation comprised medical history, physical examination, skin allergen testing, complete blood count, serum immunoglobulins, IgE levels, and pulmonary function tests. Results After implementing exclusion criteria, 29 patients were included in the final analysis. Allergic-like disorders were diagnosed in 65% of CVID patients with non-elevated serum IgE levels. Moreover, allergic CVID patients exhibited a higher prevalence of bronchiectasis on chest CT. Autoimmunity was diagnosed in 41.3% of CVID subjects. The type I allergy detected in our study was non-IgE mediated. Conclusions Timely diagnosis and stratification of allergy in CVID patients is expected to improve their outcome and quality of life, as well as promote appropriate treatment and better management of pulmonary exacerbations.

Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.

People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review. To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 31 January 2019.We also searched online trial registries. Date of latest search: 25 February 2019. All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. We identified 15 studies for possible inclusion in the review. Five studies reporting results from a total of 354 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One cross-over trial had 26 participants who received the first-arm treatment but only 15 received the second arm. One study had a low risk of bias for all criteria assessed; the remaining included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was little or no difference between treatment groups in: forced expiratory volume in one second, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48, moderate-quality evidence); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16, low-quality evidence); % weight for height, MD -0.82 (95% CI -3.77 to 2.13, low-quality evidence); body mass index, MD 0.00 (95% CI -0.42 to 0.42, low-quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96, moderate-quality evidence). Once-daily treatment in children probably improved the percentage change in creatinine, MD -8.20 (95% CI -15.32 to -1.08, moderate-quality evidence), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33, moderate-quality evidence). The included trials did not report antibiotic resistance patterns or quality of life. Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.

"Thrust out of normality"-How adults living with cystic fibrosis experience pulmonary exacerbations: A qualitative study.

To explore the experience of pulmonary exacerbation from the perspective of adults with cystic fibrosis. While management of pulmonary exacerbations is a pillar of cystic fibrosis care, little is known of patients' perspectives. Understanding the patient's experience is essential for developing and evaluating interventions in support of patient self-management. Qualitative study with longitudinal study in a subsample. The study took place from 2015-2016 in a university hospital. Eighteen patients with cystic fibrosis were included who were ≥18years of age and had no solid organ transplant. Patients' experiences were explored through semistructured interviews and analysed using framework analysis. They each participated in one interview, with a subsample (N=7) being interviewed twice during and once after antibiotic therapy. Patients (11 men and 7 women; median age 29.5years, range 19-55years; median FEV1 45%, range FEV1 23%-105%) experienced pulmonary exacerbations as disruptions of their normality, which led to a substantial increase in their emotional distress. Exacerbations represented a period of threat and domination by CF; that is, symptoms and treatment consumed energy, restricted physical activity and daily life roles. "Noting change," "waiting until antibiotics help," "returning to normality" and "establishing a new normality" characterised their descriptions of the pulmonary exacerbation trajectory. Emotional distress was the major driver for patients' self-management, and personal goals and illness beliefs influenced also patients' self-management decisions. The experienced degree and source of emotional distress are drivers for self-management decisions in patients with cystic fibrosis who experience a pulmonary exacerbation. Our data provide new understanding that will be essential to informing clinical practice, future patient-reported outcomes measures and intervention development.

Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations.

Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.

Timing of Spirometry May Impact Hospital Length of Stay for Cystic Fibrosis Pulmonary Exacerbation

The optimal timing of spirometry during hospitalization for acute pulmonary exacerbation (PEx) in patients with cystic fibrosis (CF) is unclear. We retrospectively evaluated whether measuring spirometry earlier during hospitalization was associated with a shorter length of stay (LOS). In this retrospective study, we analyzed data from the electronic medical record of CF patients 6years of age and older admitted to a single center for acute PEx requiring IV antibiotic therapy between 2009 and 2016. After excluding patient encounters with missing data on covariates, random-effects linear regression was used to predict LOS as a function of days to first pulmonary function testing (PFT), which was spirometry for our study. One thousand thirty-five hospitalizations of 242 patients met inclusion criteria, with 801 including complete data on covariates. Mean LOS was 10 ± 7 days, with mean time to first PFT of 4 ± 3 days after admission. In multivariable analysis, each additional day to first PFT was associated with 0.97 days longer LOS (95% CI 0.29, 1.64; p = 0.005). As CF researchers and clinicians work to improve management of PEx, the timing of spirometry during hospitalization remains an important question. Obtaining objective lung function data earlier during the course of therapy may provide information which can lead to reduced hospital LOS for PEx.

Does probiotic supplementation affect pulmonary exacerbation and intestinal inflammation in cystic fibrosis: a systematic review of randomized clinical trials.

Patients with cystic fibrosis (CF) usually have abnormal intestinal microbiota due to massive exposure to antibiotics. Probiotics could modify the gut microbiota and hence may affect CF management. So the aim of present systematic review was evaluation of the efficacy and safety of probiotic supplementation for the management of cystic fibrosis. We searched PubMed, Science Direct, Google Scholar, Springer Cochrane Library Databases until January 2016 for randomized controlled trials (RCTs) performed in pediatric or adult populations related to the study aim. Key words were selected based on Mesh terms. Based on the Critical Appraisal Skills Programme checklist, eligibility of included articles was evaluated. Five studies included in this review represent 188 participants with a follow up period ranging from 1 month to 6 months. The results of the included studies supporting the use of probiotics in management of pulmonary exacerbation and intestinal calprotectin in patients with cystic fibrosis. However the level of evidence was limited. The lack of high quality RCTs makes it impossible to support a general recommendation about the use of probiotics in the treatment of CF pulmonary exacerbation and intestinal inflammation.

Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis

BackgroundGiven the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols. MethodsResponse parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored. ResultsThe most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening. ConclusionsResults from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.

Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.

People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review. To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 24 June 2016. All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was no significant difference between treatment groups in: forced expiratory volume in one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48, moderate quality evidence); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16, low quality evidence); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13, low quality evidence); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42, low quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96, moderate quality evidence). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08, moderate quality evidence), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33, moderate quality evidence). The included trials did not report antibiotic resistance patterns or quality of life. Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.