Judy Bradley

Validity of a modified shuttle test in adult cystic fibrosis

BACKGROUND The purpose of this study was to provide some evidence of the validity of a modified shuttle test (MST) by comparing performance on the MST with peak oxygen consumption (V˙o 2peak) measured during a treadmill test in a group of adult patients with cystic fibrosis. METHOD Twenty patients with stable cystic fibrosis performed a ramped maximal treadmill test (STEEP protocol) and the MST using a randomised balanced design. RESULTS The relationship between the distance achieved on the MST andV˙o 2peak was strong (r = 0.95, p<0.01) with 90% of the variance in V˙o 2peak explained by the variance in MST distance. The relationship was represented by the regression equation (with 95% confidence intervals)V˙o 2peak = 6.83 (2.85 to 10.80) + 0.028 (0.019 to 0.024) × MST distance. CONCLUSION This study provides evidence of the construct validity of the MST as an objective measure of exercise capacity in adults with cystic fibrosis.

Lung clearance index: Evidence for use in clinical trials in cystic fibrosis

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the groups work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF.

Dysregulated apoptosis and NFκB expression in COPD subjects

BackgroundThe abnormal regulation of neutrophil apoptosis may contribute to the ineffective resolution of inflammation in chronic lung diseases. Multiple signalling pathways are implicated in regulating granulocyte apoptosis, in particular, NFκB (nuclear factor-kappa B) signalling which delays constitutive neutrophil apoptosis. Although some studies have suggested a dysregulation in the apoptosis of airway cells in chronic obstructive pulmonary disease (COPD), no studies to date have directly investigated if NFκB is associated with apoptosis of airway neutrophils from COPD patients. The objectives of this study were to examine spontaneous neutrophil apoptosis in stable COPD subjects (n = 13), healthy smoking controls (n = 9) and non-smoking controls (n = 9) and to investigate whether the neutrophil apoptotic process in inflammatory conditions is associated with NFκB activation.MethodsAnalysis of apoptosis in induced sputum was carried out by 3 methods; light microscopy, Annexin V/Propidium iodide and the terminal transferase-mediated dUTP nick end-labeling (TUNEL) method. Activation of NFκB was assessed using a flow cytometric method and the phosphorylation state of IκBα was carried out using the Bio-Rad Bio-Plex phosphoprotein IκBα assay.ResultsFlow cytometric analysis showed a significant reduction in the percentage of sputum neutrophils undergoing spontaneous apoptosis in healthy smokers and subjects with COPD compared to non-smokers (p < 0.001). Similar findings were demonstrated using the Tunel assay and in the morphological identification of apoptotic neutrophils. A significant increase was observed in the expression of both the p50 (p = 0.006) and p65 (p = 0.006) subunits of NFκB in neutrophils from COPD subjects compared to non-smokers.ConclusionThese results demonstrate that apoptosis is reduced in the sputum of COPD subjects and in healthy control smokers and may be regulated by an associated activation of NFκB.

Pulmonary function, inflammation, exercise capacity and quality of life in cystic fibrosis

The aim of the study was to determine the extent to which treatment induced changes in exercise capacity and quality of life (QoL) are related to spirometric measures of lung function and other measures of disease impairment. Twenty patients admitted to hospital with an exacerbation of pulmonary disease were recruited. Measures of disease impairment, disability and QoL were obtained at the beginning and end of an intravenous course of antibiotic therapy. Intravenous antibiotic treatment resulted in a significant improvement in all measures of disease impairment, disability and handicap. The only significant predictor of treatment induced change in exercise capacity was C-reactive protein (CRP) and this explained 28% of the variance in change in exercise capacity. In the case of QoL, two predictors (change in exercise capacity and sputum output) contributed significantly to the change in QoL and collectively explained 54% of the variance in QoL. Lung function provides a limited index of treatment outcome. Exercise capacity and quality of life assessment have the potential to make a significant contribution to the decision making process regarding treatment choices in cystic fibrosis and should be measured directly if a comprehensive evaluation of the effect of treatment is required.

Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques versus Acapella.

Background: The efficacy of a new airway clearance device (Acapella®) has not been previously investigated. Active cycle of breathing techniques (ACBT) is the standard airway clearance technique used in patients with bronchiectasis. Objective: The objective of this study was to compare the efficacy of ACBT with Acapella as methods of airway clearance in adults with stable, productive bronchiectasis. Methods: Twenty patients (7 males), age 58 ± 11 years (mean ± SD), FEV1 64 ± 22% predicted with stable (change of not greater than FEV1 10% predicted during 3 months prior to study), productive (history of expectoration of half an egg cup sputum/day) bronchiectasis attended the respiratory clinic on 3 days. Day 1: 40-min training session on ACBT and Acapella. Days 2 and 3: 30-min treatment session of either ACBT or Acapella. Treatment order was determined by a concealed randomization procedure. The following outcomes were measured before and after treatment spirometry, SpO2 and breathlessness by an independent assessor who was blinded to treatment order. Weight of sputum (during treatment plus 30 min after treatment), number of coughs and patient preference were also recorded. Results: No significant differences were found at baseline indicating that patients were stable. No significant differences were found between weight of sputum expectorated with ACBT treatment and weight of sputum expectorated with Acapella treatment – mean difference 0.54 g (95% CI –0.39 to 1.46). A greater proportion of patients preferred Acapella (14/20). Conclusion: Acapella is as effective a method of airway clearance as ACBT and may offer a user-friendly alternative to ACBT for patients with bronchiectasis.

Walking Exercise for Chronic Musculoskeletal Pain: Systematic Review and Meta-Analysis

OBJECTIVE To systematically review the evidence examining effects of walking interventions on pain and self-reported function in individuals with chronic musculoskeletal pain. DATA SOURCES Six electronic databases (MEDLINE, CINAHL, PsychINFO, PEDro, Sport Discus, and the Cochrane Central Register of Controlled Trials) were searched from January 1980 to March 2014. STUDY SELECTION Randomized and quasi-randomized controlled trials in adults with chronic low back pain, osteoarthritis, or fibromyalgia comparing walking interventions to a nonexercise or nonwalking exercise control group. DATA EXTRACTION Data were independently extracted using a standardized form. Methodological quality was assessed using the U.S. Preventive Services Task Force system. DATA SYNTHESIS Twenty-six studies (2384 participants) were included, and suitable data from 17 studies were pooled for meta-analysis, with a random effects model used to calculate between-group mean differences and 95% confidence intervals (CIs). Data were analyzed according to the duration of follow-up (short-term, ≤8wk postrandomization; medium-term, >2mo to 12mo; long-term, >12mo). Interventions were associated with small to moderate improvements in pain at short-term (mean difference , -5.31; 95% CI, -8.06 to -2.56) and medium-term (mean difference, -7.92; 95% CI, -12.37 to -3.48) follow-up. Improvements in function were observed at short-term (mean difference, -6.47; 95% CI, -12.00 to -0.95), medium-term (mean difference, -9.31; 95% CI, -14.00 to -4.61), and long-term (mean difference, -5.22; 95% CI, -7.21 to -3.23) follow-up. CONCLUSIONS Evidence of fair methodological quality suggests that walking is associated with significant improvements in outcome compared with control interventions but longer-term effectiveness is uncertain. With the use of the U.S. Preventive Services Task Force system, walking can be recommended as an effective form of exercise or activity for individuals with chronic musculoskeletal pain but should be supplemented with strategies aimed at maintaining participation. Further work is required for examining effects on important health-related outcomes in this population in robustly designed studies.

Quality of life and inflammation in exacerbations of bronchiectasis

Patients with bronchiectasis often have impaired quality of life (QoL), which deteriorates with exacerbations. The aim of this study was to investigate changes in QoL and how these were influenced by changes in airway physiology and inflammation in patients with bronchiectasis before and after resolution of an exacerbation. Sputum induction and a QoL questionnaire were undertaken on the first day, day 14, and 4 weeks after completion of intravenous antibiotics (day 42). Eighteen patients (12 female) were recruited, median (IQ range) age of 54 (47–60) years. There was a trend towards an improvement in lung function from visit 1 to visit 2, but this was not statistically significant. C-reactive protein (CRP) [mean (SEM)] reduced between visit 1 and visit 2 [55.4 (21.5) vs 9.4 (3.1) mg/L, P = 0.03] but did not increase significantly on visit 3 [44.4 (32.9) mg/L, P = 0.27]. The median (interquartile range) sputum cell count (×106 cells/g of sputum) decreased from visit 1 to visit 2 [21.6 (11.8–37.6)–13.3 (6.7–22.9) × 106 cells/g, respectively, P = 0.008] and increased from visit 2 to visit 3 [26.3 (14.1–33.6) × 106 cells/g, P = 0.03]. All soluble markers of inflammation significantly reduced from visit 1 to visit 2 but increased on visit 3 with the exception of TNF-α. Regarding QoL, three of the four domains (dyspnoea, emotional, mastery) significantly improved from visit 1 to visit 2 but did not change between visit 2 and visit 3. The improvements in QoL scores could not be explained by the improvements in lung function or inflammatory markers.

Lung Clearance Index Is a Repeatable and Sensitive Indicator of Radiological Changes in Bronchiectasis

RATIONALE In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy. OBJECTIVES To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis. METHODS Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2). MEASUREMENTS AND MAIN RESULTS In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life. CONCLUSIONS The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

Validity and reliability of cardiorespiratory measurements recorded by the LifeShirt during exercise tests

The LifeShirt is a novel ambulatory monitoring system that records cardiorespiratory measurements outside the laboratory. Validity and reliability of cardiorespiratory measurements recorded by the LifeShirt were assessed and two methods of calibrating the LifeShirt were compared. Participants performed an incremental treadmill test and a constant work rate test (65% peak oxygen uptake) on four occasions (>48 h apart) and wore the LifeShirt, COSMED system and Polar Sport Tester simultaneously. The LifeShirt was calibrated using two methods: comparison to a spirometer; and 800 ml fixed-volume bag. Ventilation, respiratory rate, expiratory time and heart rate recorded by the LifeShirt were compared to measurements recorded by laboratory equipment. Sixteen adults participated (6M:10 F); mean (SD) age 23.1 (2.9) years. Agreement between the LifeShirt and laboratory equipment was acceptable. Agreement for ventilation was improved by calibrating the LifeShirt using a spirometer. Reliability was similar for the LifeShirt and the laboratory equipment. This study suggests that the LifeShirt provides a valid and reliable method of ambulatory monitoring.

Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD. An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks. 75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p=0.034) and &bgr;-cryptoxanthin (p=0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane). This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.