Influenza-associated cystic fibrosis pulmonary exacerbations.
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ABSTRACT:
SUBMITTER: Ortiz JR
PROVIDER: S-EPMC2851556 | biostudies-other | 2010 Apr
REPOSITORIES: biostudies-other
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Project description:With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the disease course, prognosis, and complications. This work has now led to a number of large scale clinical trials with the goal of improving the treatment paradigm for CF pulmonary exacerbation. The primary goal of this review is to provide a summary of the pathophysiology, the clinical epidemiology, microbial epidemiology, outcome and the treatment of CF pulmonary exacerbation.
| S-EPMC7528649 | biostudies-literature
Project description:Pulmonary exacerbations lead to significant morbidity and mortality in patients with cystic fibrosis (CF). National consensus guidelines exist, but few studies report current practice in the treatment and monitoring of pulmonary exacerbations. The goal of this study was to characterize consistency and variability in the inpatient management of CF-related pulmonary exacerbations. We focused on the use of guideline-recommended maintenance therapies, antibiotic selection and treatment regimens, use of systemic corticosteroids, and frequency of lung function testing. We hypothesized that significant variability in these treatment practices exists nationally. This trial was a retrospective cross-sectional study. It included patients with CF aged ≤18 years hospitalized for pulmonary exacerbations between July 1, 2010, and June 30, 2015, at hospitals within the US Pediatric Health Information System database that are also Cystic Fibrosis Foundation-accredited care centers. One exacerbation per patient was randomly selected over the 5-year study period. From 38 hospitals, 4827 individual pulmonary exacerbations were examined. Median length of stay was 10.0 days (interquartile range, 6-14.0 days). Significant variation was seen among centers in the use of hypertonic saline (11%-100%), azithromycin (5%-83%), and systemic corticosteroids (3%-61%) and in the frequency of lung function testing. Four different admission antibiotic regimens were used >10% of the time, and the most commonly used admission antibiotic regimen comprised 2 intravenous antibiotics with no additional oral or inhaled antibiotics (29%). Significant variation exists in the treatment and monitoring of pulmonary exacerbations across Pediatric Health Information System-participating, Cystic Fibrosis Foundation-accredited care centers. Results from this study can inform future research working toward standardized inpatient pulmonary exacerbation management to improve CF care for children and adolescents.
| S-EPMC5472380 | biostudies-literature
Project description: Not available
| S-EPMC9342853 | biostudies-literature
Project description:Background.Characterization of the role of respiratory viral pathogens on cystic fibrosis (CF) pulmonary disease is needed. We aimed to determine the association of influenza and respiratory syncytial virus (RSV) activity with risk of pulmonary exacerbation (PEx) in persons with CF in the United States.Methods.We conducted a cohort study from January 2003 to March 2009 using the CF Foundation Patient Registry merged with Centers for Disease Control and Prevention respiratory virus surveillance data. The primary goal was to determine the association between regional influenza or RSV detections with risk of PEx requiring intravenous antibiotics or hospitalization. We analyzed outcomes by geographic region and week of event using multivariable regression models adjusted for demographic and clinical predictors of PEx stratified for children (<18 years) and adults (≥18 years) to calculate relative risks (RRs) of PEx.Results.There were 21022 individuals (52% male) in the CF patient cohort in 2003 comprised of 12702 children and 8320 adults. The overall incidence rate of PEx was 521.9 per 10000 person-months. In children, a 10% increase in the proportion of surveillance tests positive for influenza or RSV was significantly associated with increased PEx risk (RR, 1.02; 95% confidence interval [CI], 1.01-1.03) and (RR, 1.05; 95% CI, 1.02-1.07), respectively. In adults, surveillance tests positive for influenza (RR, 1.02; 95% CI, 1.01-1.02), but not RSV (RR, 0.99; 95% CI, .98-1.01), had a significant association with PEx risk.Conclusions.Our large CF population-based cohort demonstrated a significant association between PEx risk and influenza activity in children and adults and with RSV activity in children.
| S-EPMC5848232 | biostudies-literature
Project description:Recent literature suggests vitamin D has an effect on lung function and on the lung's ability to fight infection, both important in the cystic fibrosis (CF) population as predictors of morbidity and mortality.Our study assessed associations between vitamin D and % predicted lung function, pulmonary exacerbations, and first Pseudomonas aeruginosa infection in children with CF. We hypothesized that children with CF who have 25-hydroxy vitamin D (25-OHD) levels less than 30 ?g/L would have lower % predicted lung function and more pulmonary exacerbations than those with 25-OHD greater than or equal to 30 ?g/L.This retrospective longitudinal study of 130 children aged 6 to 18 years between 2000 and 2012 examined 25-OHD levels classed in three vitamin D groups: sufficient (?30 ?g/L), insufficient (20-29 ?g/L), and deficient (<20 ?g/L). Longitudinal models followed individuals' changing vitamin D groups over time to compare numbers of pulmonary exacerbations (defined by hospitalization), incidence of first P. aeruginosa infection, and % predicted lung function. Cross-sectional comparisons between vitamin D groups were performed at ages 8, 12, and 16 years.The prevalence of vitamin D deficiency and insufficiency increased slowly through adolescence. The rate of exacerbations for the deficient vitamin D group, aged 15 to 18 years, was 13.1 per 10 patient-years, significantly higher than 4.3 per 10 patient-years for the insufficient and sufficient vitamin D groups (P < 0.05), which were not significantly different There were no differences between vitamin D groups in pulmonary function or incidence of first P. aeruginosa infection, which was about 2 per 10 patient-years.Higher 25-OHD levels in children with CF were associated with lower rates of pulmonary exacerbations and, in adolescents, higher FEV1.
| S-EPMC3972970 | biostudies-other
Project description:Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis. The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We aimed to assess the association between pulmonary artery enlargement (defined as pulmonary artery diameter to ascending aorta diameter [PA:A] ratio >1), a marker of pulmonary vascular disease, and exacerbations.In this cohort study, we used clinical, CT imaging, and prospective exacerbation data from a previous prospective clinical trial (derivation cohort) and from The Prince Charles Hospital (TPCH; Brisbane, QLD, Australia) cystic fibrosis registry (validation cohort). In our derivation cohort, we included adults aged 18 years or older with cystic fibrosis and at least one CFTR nonsense mutation, who were enrolled in the trial between Sept 8, 2009, and Nov 30, 2010, randomly assigned to receive placebo, and had baseline CT imaging. Our validation cohort included adult patients with cystic fibrosis who had CT imaging performed between Jan 1, 2002, and Dec 31, 2014. We measured the PA:A ratio at the level of the pulmonary artery bifurcation on CT scans. Patients in each cohort were separated into two groups on the basis of PA:A ratio (>1 or ?1) and were followed up for 1 year in the derivation cohort and 2 years in the validation cohort. The primary endpoint was the development of one or more acute pulmonary exacerbations during follow-up. We used linear and logistic regression models to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine the time to first exacerbation in the validation cohort.37 (50%) of 74 patients in the derivation cohort and 89 (47%) of 190 patients in the validation cohort had enlarged pulmonary arteries (PA:A>1). 50 (68%) patients in the derivation cohort had one or more exacerbations at 1 year and 133 (70%) patients in the validation cohort had one or more exacerbations at 2 years. At baseline, patients with pulmonary artery enlargement were younger than those without enlargement in both cohorts and had elevated sweat chloride concentrations in the derivation cohort (100·5 mmol/L [SD 10·9] vs 90·4 mmol/L [19·9]; difference 10·1 mmol/L [95% CI 2·5-17·7], p=0·017). Pulmonary artery enlargement was associated with exacerbations in the derivation cohort (odds ratio 3·49 [95% CI 1·18-10·3], p=0·023) when adjusted for sex, body-mass index (BMI), forced expiratory volume in 1 s (FEV1), and PA:A greater than 1, and in the validation cohort (2·41 [1·06-5·52], p=0·037) when adjusted for sex, BMI, chronic Pseudomonas aeruginosa infection, FEV1/FVC (forced vital capacity), PA:A greater than 1, and previous exacerbation. The time to first exacerbation was shorter in patients with enlarged pulmonary arteries than in those with normal-sized pulmonary arteries in the validation cohort (hazard ratio 1·66 [95% CI 1·18-2·34], p=0·0038) in unadjusted analysis, but not when adjusted for sex, BMI, exacerbations within 1 year before index CT scan, FEV1/FVC, and chronic P aeruginosa infection (1·14 [0·80-1·62], p=0·82).Pulmonary artery enlargement is prevalent in adult patients with cystic fibrosis and was associated with acute pulmonary exacerbation risk in two well characterised cohorts. The PA:A ratio could be a predictive marker in cystic fibrosis.US National Heart, Lung, and Blood Institute/National Institutes of Health, Cystic Fibrosis Foundation, the University of Alabama at Birmingham, and the Queensland Health Fellowship.
| S-EPMC5672808 | biostudies-literature
Project description:BackgroundPulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.ObjectiveTo determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.MethodsExpectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.ResultsThirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = -0.67, p<0.001), decreased FEV(1%) predicted (r = 0.49, p = 0.03) and increased CRP (r = -0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.ConclusionsAnaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.
| S-EPMC3639911 | biostudies-literature
Project description:RATIONALE:People with CF treated with IV antibiotics for a pulmonary exacerbation (PEx) frequently fail to recover to baseline FEV1 . The long-term impact of these events has not been studied. OBJECTIVES:To determine if a patient's spirometric recovery after a PEx is associated with time to next PEx within 1 year, the spirometric recovery after the next PEx, and/or the number of PEx episodes in the next 3 years. METHODS:We used data from the CF Foundation Patient Registry from 2004 to 2011. We randomly selected one PEx per patient that met inclusion/exclusion criteria. Patients were defined as Non-Responders if their best FEV1 (in liters) recorded in the 3 months after the PEx was <90% of the best FEV1 (in liters) in the 6 months before the PEx. We compared Responders and Non-Responders using multivariable regression models. RESULTS:We randomly chose 13?954 PEx episodes that met inclusion/exclusion criteria. A total of 2?762 (19.8%) patients were classified as Non-Responders. Non-Responders had a shorter median time to the next PEx, 235 (95%CI 218, 252) days, versus >365 days for Responders. Thirty-four percent of Non-Responders at the initial PEx were also Non-Reponders at the next PEx, versus 20% of Responders at the initial PEx. Non-Responders had more PEx episodes over the next 3 years, 4.99 (95%CI 4.84, 5.13), than Responders, 3.46 (95%CI 3.41, 3.51). CONCLUSIONS:Poor recovery after a PEx is associated with a shorter time to the next PEx, increased risk of poor recovery at a second PEx, and more frequent subsequent PEx treatments.
| S-EPMC5639928 | biostudies-literature
Project description:IntroductionPulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.MethodsWe prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.ResultsOut of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.ConclusionOur results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.
| S-EPMC3922941 | biostudies-literature
Project description: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.
| S-EPMC10031862 | biostudies-literature