Breathlessness catastrophizing relates to poorer quality of life in adults with cystic fibrosis

Background

Cystic Fibrosis (CF) is the most common genetic disease affecting children and young adults in Canada. It is a multi-system disease, however lung disease is largely responsible for mortality. Treatment advances have resulted in increased life expectancy and a subsequent need to better understand psychosocial issues associated with quality of life in adults living with CF. Emerging research suggests that anxiety and depression are related to poorer health-related quality of life (HRQoL) in CF patients, but there is little research examining cognitive processes, such as breathlessness catastrophizing. The present study addresses this gap in the literature. Methods: Participants in this study are based on a convenience sample of patients recruited during their regular CF clinic appointments at a tertiary care center. Forty-five adults (M_age?=?30.73?years) completed measures of lung function, depression, anxiety, pain, breathlessness catastrophizing, and HRQoL at one time point. Results: Results of a hierarchical multiple regression indicate that increased breathlessness catastrophizing was related to poorer HRQoL, after controlling for lung function, depression, anxiety, and pain (p?<?.05). Depression, pain, and breathlessness catastrophizing all emerged as significant unique predictors of HRQoL. Conclusions: Breathlessness catastrophizing is a potential target for clinical intervention and might impact HRQoL. Further research on breathlessness catastrophizing in CF is warranted including longitudinal studies to examine the mechanisms by which breathlessness catastrophizing relates to HRQoL and treatment outcomes in CF.     

Physical activity and associations with clinical outcome measures in adults with cystic fibrosis; a systematic review

BackgroundPhysical activity (PA) is important in the management of Cystic Fibrosis (CF) and is associated with a number of beneficial effects. PA assessment is not commonplace or consistent in clinical practice, therefore understanding of PA in adults with CF remains limited. The purpose of this review was to evaluate PA levels in this population and compare PA to global recommendations and non-CF peers.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilised to inform the review process. Original research was identified and screened against inclusion/exclusion criteria. Quality was assessed, data extracted and a narrative synthesis undertaken to describe the findings.ResultsAdults with CF did not achieve recommended PA guidelines and step count targets in 5/8 studies where assessment was possible. No significant differences in PA were found between CF and non-CF peers in 3/5 studies. Associations between PA and improved lung function were inconsistent with 4/9 studies finding a positive association. Evidence for an association between PA and higher exercise capacity was stronger with all 4 studies reviewed reporting a positive association. Quality ratings were low across all studies.ConclusionsPA in adults with CF is largely comparable to their non-CF peers, despite being insufficiently active to achieve PA recommendations. Assessment tools used and outcomes reported are variable, many of which do not provide sufficient information to assess relevant components of PA. There is a requirement for high quality studies designed specifically to explore PA in adults with CF, ideally employing standardised PA assessment methods.     

Sputum neutrophils in cystic fibrosis patients display a reduced respiratory burst

BackgroundFew data exist on the functional activity of airway neutrophils in the milieu of the cystic fibrosis (CF) lung. We assessed reactive oxygen species (ROS) production by sputum neutrophils and the relationship to neutrophil viability. Identical assessments were made on peripheral blood neutrophils from CF patients.MethodsROS production in sputum neutrophils was assessed in 31 CF patients at varying phases of clinical disease using flow cytometry. Twenty patients provided blood samples (including 16 who also provided a matched sputum sample). Neutrophil viability was determined using dual annexin V (apoptosis) and propidium iodide (necrosis) staining. Comparative peripheral blood data were obtained from 7 healthy controls.ResultsROS production was reduced in sputum compared to blood neutrophils and they demonstrated a higher level of necrosis. Subpopulations of neutrophils with different ROS production capacity were apparent in peripheral blood. Lung function was positively associated with both the proportion of blood neutrophils demonstrating increased ROS production and the proportion of apoptotic sputum neutrophils.ConclusionsCF airway neutrophils display functional exhaustion. Healthier lungs in CF appear to be associated with subpopulations of blood neutrophils with increased oxidative burst capacity and evidence for increased neutrophil apoptosis within the airway.     

Predicting outcome following pulmonary resection in cystic fibrosis patients

A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years. Fourteen patients with CF, ranging from 3 to 30 years of age, underwent 17 pulmonary resections. Indications for surgery were persistent lobar or pulmonary atelectasis and bronchiectasis requiring multiple hospitalizations and unresponsive to medical therapy (n = 13), bronchopleural fistula (n = 2), or hemoptysis not responding to medical therapy or selective embolization (n = 2). Thirteen lobectomies and four pneumonectomies were performed. Only two resections were on the left side and 11 right upper lobectomies were performed. Postoperative hospitalization ranged from 5 to 21 days (mean, 8.5 days). Preoperative pulmonary function tests showed widely divergent function in these patients. Forced expiratory volume (FEV1) ranged from 11% to 88% whereas forced vital capacity (FVC) ranged from 20% to 100% of predicted values. Oxygen saturation ranged from 86% to 99%. Although there was no significant difference in preoperative and postoperative FVC or O2 saturation, there was a significant (P less than .003) decrease in the postoperative FEV1. In the 12 surviving patients followed for at least 1 year, there was also a significant reduction (P less than .001) in the number of hospitalizations required due to pulmonary exacerbations from an average 2.2 admissions per year (range, 0.44 to 3.5 admissions per year) to 1.1 admissions per year (range, 0 to 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early referral to cystic fibrosis specialist centre impacts on respiratory outcome

BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.     

Autoantibody response to BPI predict disease severity and outcome in cystic fibrosis.

BACKGROUND: Autoantibodies against bactericidal permeability increasing protein (BPI-ANCA) are frequently present in cystic fibrosis patients and have been reported to be associated to colonization with Pseudomonas (P) aeruginosa and lung damage. In the present study, we investigated BPI-ANCA as a prognostic marker and its relation to P. aeruginosa colonization and lung function. METHODS: BPI-ANCA, measured by ELISA, was examined relative to lung function and microbiological findings. The prognostic value of BPI-ANCA was assessed in 46 adult patients followed for 1.2-8.9 years. The cross-sectional investigation was performed in 366 patients (age 0.5-55). RESULTS: The presence of BPI-ANCA predicted poor prognosis. An adverse outcome occurred in 15/28 BPI-ANCA positive patients and in 2/18 BPI-ANCA negative patients (p=0.01). This result remained valid when the patients were stratified according to lung function (p=0.03). Findings of BPI-ANCA were correlated to P. aeruginosa colonization and lung damage. Development of BPI-ANCA occurred after colonization with P. aeruginosa. All colonized patients did not develop BPI-ANCA. The BPI-ANCA levels were fairly stable during the disease course, but decreased significantly following lung transplantation. CONCLUSION: BPI-ANCA responses follow colonization with P. aeruginosa and may be predictive for lung damage.     

Long term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis

Methods: A retrospective longitudinal study was performed to compare the clinical outcome over a period of 1 year of all patients attending the Manchester Adult CF Unit who received intravenous antibiotics at home or in hospital. The primary outcome measure was percentage change in forced expiratory volume in 1 second (FEV₁) at the end of the 1 year period. Baseline "best" and "average" FEV₁ values were established for each patient for the year before the study. The secondary outcome measures were percentage changes in forced vital capacity (FVC) and body weight.

Results: A total of 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year there had been a mean percentage decline in FEV₁ compared with the baseline "average" for patients treated mostly at home but an improvement in patients treated mostly in hospital (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). For all patients there was a mean percentage decline in FEV₁ from the baseline "best" value. For each course of treatment the mean percentage improvements in FEV₁ at the end of the course from the start of the course were significantly higher for patients treated in hospital than for those treated at home.

Conclusions: Clinical outcome, as defined by spirometric parameters and body weight, was better after a course of treatment in hospital than after home treatment, and this benefit was maintained over 1 year of treatment. The results suggest that patients treated at home need closer supervision.

     

Delayed publication of clinical trials in cystic fibrosis

BackgroundWhen the publication of important trial data is delayed, or data are never published, this will prevent the proper practice of evidence based medicine through robust systematic reviews. Clinical trial registries allow researchers to interrogate the trial protocol and afford the opportunity to identify studies that have been completed and so determine the time lag between completion and publication.MethodsWe searched ClinicalTrials.gov with the keywords ‘cystic fibrosis’. Intervention trials which had completed 1st Jan 1998–31st Dec 2010 were selected. Time to publication in a peer-reviewed journal was calculated. Survival analyses using the log rank test were undertaken.ResultsWe identified 142 records. Of these, 62 had full paper publications. The median time to publication was 3.25 years. Phase of study (phase one studies more delayed, p = 0.024) but not source of funding (p = 0.34) was associated with time to publication.ConclusionsClinical trials in cystic fibrosis take a considerable amount of time to report their findings. More importantly, a large number of trials fail to report at all.     

Methylomic correlates of autophagy activity in cystic fibrosis

Autophagy is a highly regulated, biological process that provides energy during periods of stress and starvation. This conserved process also acts as a defense mechanism and clears microbes from the host cell. Autophagy is impaired in Cystic Fibrosis (CF) patients and CF mice, as their cells exhibit low expression levels of essential autophagy molecules. The genetic disorder in CF is due to mutations in the cystic fibrosis transmembrane conductance regulator (cftr) gene that encodes for a chloride channel. CF patients are particularly prone to infection by pathogens that are otherwise cleared by autophagy in healthy immune cells including Burkholderia cenocepacia (B. cenocepacia). The objective of this study is to determine the mechanism underlying weak autophagic activity in CF macrophages and find therapeutic targets to correct it. Using reduced representation bisulfite sequencing (RRBS) to determine DNA methylation profile, we found that the promoter regions of Atg12 in CF macrophages are significantly more methylated than in the wild-type (WT) immune cells, accompanied by low protein expression. The natural product epigallocatechin-3-gallate (EGCG) significantly reduced the methylation of Atg12 promoter improving its expression. Accordingly, EGCG restricted B. cenocepacia replication within CF mice and their derived macrophages by improving autophagy and preventing dissemination. In addition, EGCG improved the function of CFTR protein. Altogether, utilizing RRBS for the first time in the CF field revealed a previously unrecognized mechanism for reduced autophagic activity in CF. Our data also offers a mechanism by which EGCG exerts its positive effects in CF.     

Pre-transplant mechanical ventilation and outcome in patients with cystic fibrosis.

Mechanical ventilation for ventilatory failure has been considered a relative contraindication to subsequent lung transplantation. The purpose of this study was to test the hypothesis that patients with cystic fibrosis (CF) who are intubated and mechanically ventilated before transplantation have poorer post-transplant outcomes than do patients who are not ventilated.We compared the outcomes of 8 patients with CF who underwent mechanical ventilation for 62 +/-20 days (range, 3-153 days) before bilateral lung transplantation with outcomes of 24 patients with CF who did not undergo pre-transplant mechanical ventilation.Although time to extubation after transplantation was prolonged significantly (11 vs 4 days) for the pre-transplant ventilated group, days to hospital discharge, forced expiratory volume in 1 second (percent predicted) at 1 year after transplantation, and post-transplant survival as determined using the Kaplan-Meier method did not differ statistically between the 2 groups.Patients with CF who undergo pre-transplant endotracheal intubation and mechanical ventilation for respiratory failure have outcomes that do not differ significantly from those of patients with CF who do not require invasive ventilatory support before bilateral lung transplantation.     

Pregnancy outcome in women with cystic fibrosis and poor pulmonary function

BackgroundTo investigate how poor pre-gestational pulmonary function influenced pregnancy outcome and clinical status evolution in women with cystic fibrosis.MethodsPregnancies in women without lung transplantation with a first delivery reported to the French cystic fibrosis registry between 2000 and 2012 were identified. Pregnancy outcomes and clinical trends (body mass index – BMI, and pulmonary function) over a 4-year follow-up in women with poor pre-gestational pulmonary function, defined as forced expiratory volume (FEV₁) ≤ 50%, were compared to those in women with FEV₁ ˃ 50%.ResultsA total of 149 women had a first delivery and 36 (24.2%) of these had pre-gestational FEV₁ ≤ 50%. There was no significant difference in age or frequency of assisted conception between the 2 groups. The rate of cesarean section was significantly higher in women with FEV₁ ≤ 50% (43.7% vs. 21.1%, p = .01). The frequency of preterm birth did not differ significantly between the two groups, but median infant birthweight was significantly lower in women with FEV₁ ≤ 50% (2705 g; range: 650–3700 vs. 3044 g; range: 1590–3860, p = .003). Despite significantly lower FEV₁ and BMI the year before pregnancy for women with poor pulmonary function, the decline in these parameters during the study period did not differ significantly between the two groups.ConclusionPoor pre-gestational pulmonary function in women with cystic fibrosis was associated with a higher rate of cesarean section and a clinically significant impact on fetal growth, but was not associated with more important pulmonary and nutritional decline over the study period.     

Sputum induction as a research tool for sampling the airways of subjects with cystic fibrosis

BACKGROUND: Sputum induction (SI) has proved to be a reliable non-invasive tool for sampling inflammatory airway contents in asthma, with distinct advantages over collection of expectorated sputum (ES) and bronchoalveolar lavage (BAL). A study was undertaken to evaluate the safety of SI and to assess if it might be an equally valuable outcome tool in patients with cystic fibrosis (CF). METHODS: The safety of the procedure was examined and sample volume, cell counts, cytokine concentrations, and bacterial culture results obtained by SI, spontaneous ES, and fibreoptic bronchoscopy were compared in 10 adults with CF. RESULTS: SI was well tolerated and was preferred to BAL by all subjects. The mean (SE) sample volume obtained by SI was significantly greater than ES (6.74 (1.46) ml v 1.85 (0.33) ml, p = 0.005). There was no significant difference in the number of cells per ml of sample collected. There was a difference in the mean (SD) percentage of non-epithelial, non-squamous cells collected (67 (28)%, 86 (21)%, and 99 (1)% for ES, SI, and BAL, respectively). These percentage counts were different between ES and both SI and BAL (p=0.03 and p=0.006, respectively). Cell differential counts (excluding squamous cells) from all collection methods were similar (mean (SD) 84 (9)%, 87 (7)%, and 88 (11)% polymorphonuclear cells for ES, SI, and BAL, respectively). The concentrations of interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha were the same in all three samples when corrected for dilution using urea concentration. The test specific detection rate for recovery of bacteriological pathogens was 79% for SI, 76% for ES, and 73% for BAL. CONCLUSION: SI offers safety advantages over BAL and may be a more representative airway outcome measurement in patients with CF.     

Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults.

BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period. The best forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of decline calculated. RESULTS: The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.     

Neutrophil respiratory burst activity is not exaggerated in cystic fibrosis

BackgroundExaggerated neutrophil-dominated inflammation underlies progressive cystic fibrosis (CF) lung disease. Older studies reported a defective respiratory burst in CF, but more recent studies suggest neutrophil function is normal.MethodsWe measured the amount and rate of reactive oxygen species (ROS) during PMA-stimulated respiratory burst activity in children [70 CF, 13 disease controls, 19 health controls] and adults [31 CF, 14 health controls] in neutrophils harvested from peripheral blood. Blood was collected from participants with CF when clinically stable (60 children, 9 adults) and on hospital admission (38 children, 24 adults) and discharge (18 children, 21 adults) for acute pulmonary exacerbations.ResultsWhen clinically stable, children with CF had lower ROS production [median 318,633, 25% 136,810 - 75% 569,523 RLU] than disease controls [median 599,459, 25% 425,566 - 75% 730,527 RLU] and healthy controls [median 534,073, 25% 334,057 - 75% 738,593 RLU] (p = 0.008). The rate of ROS production was also lower (p = 0.029). In neither children nor adults with CF did ROS production increase on hospital admission for acute pulmonary exacerbation, nor fall prior to discharge. There were no associations between ROS production and high-sensitivity C-reactive protein (indicating systemic inflammation) in either children or adults with CF.ConclusionsOur data do not support a role for exaggerated respiratory burst activity contributing to the exaggerated neutrophil-dominated inflammation seen with CF lung disease.     

Impaired gastric myolectrical activity in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is frequently associated with gastrointestinal complaints that can be due to gastrointestinal dysmotility. Electrogastrography (EGG) is an attractive, non-invasive procedure to assess gastric electric activity. The aims of our study were to investigate EGG abnormalities in pancreatic sufficient and pancreatic insufficient CF patients, and to examine whether EGG correlates with gastric emptying as assessed by scintigraphy. METHODS: EGG was performed in 23 CF patients (12 pancreatic sufficient patients, 11 pancreatic insuffficient) by using cutaneous recording pre- and postprandialy. Pre- and postpostprandial EGG indexes were compared to 19 healthy control patients. Gastric emptying was assessed simultaneously by gastric scintigraphy in 11 of the 23 CF patients. Six patients underwent a repeated scintigraphy recording following a month of treatment with cisapride. RESULTS: Abnormal patterns of EGG were found in 78.3% of CF patients compared to 31.3% of controls during fasting (p相似文献   

Utilization of electronic patient-reported outcome measures in cystic fibrosis research: Application to the GALAXY study

BACKGROUNDThe Food and Drug Administration considers patient-reported outcome measures (PROMs) an essential part of clinical research studies for approval of new drugs and new indications for existing drugs. GALAXY evaluated the feasibility of electronic PROMs (ePROMS) to conduct a comprehensive evaluation of gastrointestinal (GI) symptoms in persons with cystic fibrosis (pwCF).METHODSThree validated GI ePROMs (PAC-SYM, PAGI-SYM and PAC-QOL) were combined with a Stool-Specific questionnaire to make up the GALAXY ePROMs and administered prospectively across 26 CF centers in the United States. The ePROMs were completed at enrollment visit and then electronically at weeks 1, 2 and 4. PwCF at least 2 years and older were eligible for the study. Reminders were only provided by the mobile application during the study window.RESULTSThere were 402 participants enrolled in GALAXY. Of those, 169 (42%) were under 18 years old and 193 (48%) were female. The proportion of all follow-up weeks with at least 1 ePROM fully completed was 80%, slightly higher in those ≥18 years of age (82.5%) compared to those <18 years of age (76.5%). When assessing the completion for all 4 ePROMs, the percentage was 77.6%, also higher among those ≥18 year of age (81.5% versus 72.2% for < 18 years of age).CONCLUSIONUsing ePROMs, our study demonstrated that GI symptoms can be feasibly collected with good reproducibility and with minimal involvement of research coordinator time. This mechanism of symptom collection may provide an efficient tool for future CF trials.