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Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

ABSTRACT: Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterise the heterogeneity of PEx care in adults and paediatrics, and correlate it with measures of clinical response including short-term and long-term lung function changes, change in symptom severity score and time to next intravenous antibiotic therapy.Data were used from a prospective observational study of patients with CF ?10?years of age enrolled at six sites between 2007 and 2010. All were started on intravenous antibiotics for a clinically diagnosed PEx. Analysis of variance, logistic and Cox regression were used to examine the association of treatment factors with short-term and long-term clinical response.Of 123 patients with CF (60% women, aged 23.1±10.2?years), 33% experienced <10% relative improvement in FEV1 during treatment, which was associated with failing to recover baseline lung function 3?months after treatment (OR=7.8, 95% CI 1.9 to 31.6, p=0.004) and a longer time to next intravenous antibiotic (HR=0.48, 95% CI 0.27 to 0.85, p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy, which had a median recurrence time of 143?days.Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or intravenous antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures.NCT00788359 (www.clinicaltrials.gov).

SUBMITTER: Heltshe SL

PROVIDER: S-EPMC4778725 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

Heltshe Sonya L SL Goss Christopher H CH Thompson Valeria V Sagel Scott D SD Sanders Don B DB Marshall Bruce C BC Flume Patrick A PA

Thorax 20150424 3

<h4>Background</h4>Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterise the heterogeneity of PEx care in adults and paediatrics, and correlate it with measures of clinical response including short-term and long-term lung function changes, change in symptom severity score and time to next intravenous antibiotic therapy. ...[more]

PMID: 25911223

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Project description: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.

Project description:Rationale: Pulmonary exacerbations (PExs) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PExs are treated with intravenous antibiotics, including tobramycin. CF care guidelines recommend continuing chronic maintenance medications during PEx treatment. Azithromycin (AZM) is one of the most widely prescribed chronic medications for CF in the United States. Recent evidence has identified a potential antagonistic relationship between AZM and tobramycin.Objectives: To determine whether, among PEx treated with intravenous tobramycin, concomitant AZM use is associated with worse clinical outcomes.Methods: Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS)-linked dataset. People with CF age 6-21 years were included if they were hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was used to minimize the effects of confounders, including indication bias. Associations of concomitant treatment with AZM and lung function outcomes were determined using linear mixed-effect models and generalized estimating equations. Cox proportional hazard regression models were used to evaluate associations with time to next PEx.Results: Among the 10,660 people with CF included in the CFFPR-PHIS-linked dataset, 2,294 children and adolescents with 5,022 PExs that had intravenous tobramycin use were identified. A little less than half (n = 2,247; 45%) of all PExs were treated concomitantly with AZM and intravenous tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with intravenous tobramycin was associated with a significantly lower absolute improvement in percentage-predicted forced expiratory volume in 1 second (ppFEV1) (-0.93%; 95% confidence interval [CI], -1.78 to -0.07; P = 0.033), a lesser odds of returning to 90% or more of baseline ppFEV1 (odds ratio, 0.79; 95% CI, 0.68-0.93; P = 0.003), and a shorter time to next PEx requiring intravenous antibiotics (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < 0.001) compared with intravenous tobramycin use without concomitant AZM.Conclusions: Concomitant AZM and intravenous tobramycin use for in-hospital PEx treatment was associated with poorer clinical outcomes than treatment with intravenous tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.

Project description:BackgroundPulmonary exacerbations (PExs) are clinically important in people with cystic fibrosis (CF). Multiple definitions have been used for PEx, and this scoping review aimed to identify the different definitions reported in the literature and to ascertain which signs and symptoms are commonly used to define them.MethodsA search was performed using Embase, MEDLINE, Cochrane Library, Scopus and CINAHL. All publications reporting clinical trials or prospective observational studies involving definitions of PEx in people with CF published in English from January 1990 to December 2022 were included. Data were then extracted for qualitative thematic analysis.ResultsA total of 14 039 records were identified, with 7647 titles and abstracts screened once duplicates were removed, 898 reviewed as full text and 377 meeting the inclusion criteria. Pre-existing definitions were used in 148 publications. In 75% of papers, an objective definition was used, while 25% used a subjective definition, which subcategorised into treatment-based definitions (76%) and those involving clinician judgement (24%). Objective definitions were subcategorised into three groups: those based on a combination of signs and symptoms (50%), those based on a predefined combination of signs and symptoms plus the initiation of acute treatment (47%) and scores involving different clinical features each with a specific weighting (3%). The most common signs and symptoms reported in the definitions were, in order, sputum production, cough, lung function, weight/appetite, dyspnoea, chest X-ray changes, chest sounds, fever, fatigue or lethargy and haemoptysis.ConclusionWe have identified substantial variation in the definitions of PEx in people with CF reported in the literature. There is a requirement for the development of internationally agreed-upon, standardised and validated age-specific definitions. Such definitions would allow comparison between studies and effective meta-analysis to be performed and are especially important in the highly effective modulator therapy era in CF care.

Dataset Information

Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

Publications

Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

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