Ambulatory transcutaneous carbon dioxide monitoring for children with neuromuscular disease.

OBJECTIVE: Early screening and diagnosis of nocturnal hypoventilation can slow progression to diurnal hypercapnia and mortality in children with neuromuscular disease (NMD). However, gold standard, laboratory-based polysomnography (PSG) testing is a limited resource. Therefore, we evaluated the diagnostic accuracy of ambulatory transcutaneous carbon dioxide (tcCO2) monitoring used in the home compared to PSG in children with NMD. METHODS: Prospective, cross-sectional study in children 0-18 years old with a confirmed diagnosis of NMD and a clinically indicated need for PSG. Ambulatory tcCO2 was assessed by a respiratory therapist in participant's homes. Demographics, and PSG (including tcCO2). RESULTS: We enrolled 39 children with NMD; 3 had unusable ambulatory tcCO2 data because of failure of drift correction on the machine (n = 2) or an air bubble (n = 1). The remaining 36 patients aged 11 months to 16 years (median (IQR) 12.5 years (6.0-15.8)) had ambulatory tcCO2 and outpatient level 1 PSG data. Ambulatory tcCO2 monitoring had a sensitivity of 20.0% (95% confidence interval [CI] 0.5-71.6%) and a specificity of 93.5% (95% CI 78.6-99.2%). Almost all children and/or parents (34/36, 94%) preferred ambulatory monitoring over in-hospital PSG. CONCLUSIONS: Ambulatory transcutaneous carbon dioxide monitoring was not sufficiently accurate as a clinical tool for the diagnosis of nocturnal hypoventilation our cohort of children with neuromuscular disease despite being preferred over PSG by both children and parents.

Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine.

BACKGROUND: Challenges in developing drugs for pancreatic ductal adenocarcinoma (PDAC) include obtaining metastatic cancer tissue for research and validating biomarkers predicative for personalised therapeutic decisions. We have recently developed a novel therapeutic model for PDAC to address these challenges based on the isolation of viable PDAC cells derived from ascites fluid. METHODS: Ascites fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro. RESULTS: We successfully established ascites-derived primary cell cultures within 2-7 days from 92% (93 out of 101) of the ascites fluid samples obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell cultures were identified and characterised. We observed a wide range in doubling times and migration properties among the different patient-derived cell cultures. The diverse nature of each individual patient's cell cultures was further demonstrated by differences in therapeutic susceptibility and resistance. The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts. CONCLUSIONS: We have developed a unique ascites-derived PDAC primary cell culture model. This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.

Nocturnal noninvasive positive pressure ventilation in stable COPD: a systematic review and individual patient data meta-analysis.

INTRODUCTION: The effects of nocturnal noninvasive positive pressure ventilation (NIPPV) in patients with stable chronic obstructive pulmonary disease (COPD) remain controversial. METHODS: The Cochrane Airways group Register of Trials, MEDLINE, EMBASE and CINAHL were searched up to August 2012. Individual patient data from randomised controlled trials on NIPPV outcomes were selected for two separate meta-analyses: the first with follow-up of 3 months and the second with 12 months of follow-up. Additionally, subgroup analyses within the NIPPV group comparing IPAP levels, compliance and levels of hypercapnia on change in PaCO2 after 3 months were performed. RESULTS: Seven trials (245 patients) were included. All studies were considered of moderate to high quality. No significant difference was found between NIPPV and control groups after 3 or 12 months of follow-up when looking at PaCO2 and PaO2, 6-minute walking distance, health-related quality-of-life, forced expiratory volume in 1 s, forced vital capacity, maximal inspiratory pressure and sleep efficiency. Significant differences in change in PaCO2 after 3 months were found for patients ventilated with IPAP levels of at least 18 cm H2O, for patients who used NIPPV for at least 5 h per night as well as for patients with baseline PaCO2 of at least 55 mm Hg when compared to patients with lower IPAP levels, poorer compliance or lower levels of hypercapnia. DISCUSSION: At present, there is insufficient evidence to support the application of routine NIPPV in patients with stable COPD. However, higher IPAP levels, better compliance and higher baseline PaCO2 seem to improve PaCO2.

Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos.

BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies. METHODS: Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain. RESULTS: Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment. CONCLUSION: The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening.

Resistance or sensitivity of Wilms' tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target.

Wilms' tumor (WT), the most frequent renal solid tumor in children, has been linked to aberrant Wnt signaling. Herein, we demonstrate that different WTs can be grouped according to either sensitivity or resistance to an antibody (Ab) specific to frizzled7 (FZD7), a Wnt receptor. In the FZD7-sensitive WT phenotype, the Ab induced cell death of the FZD7(+) fraction, which in turn depleted primary WT cultures of their clonogenic and sphere-forming cells and decreased in vivo proliferation and survival on xenografting to the chick chorio-allantoic-membrane. In contrast, FZD7-resistant WT in which no cell death was induced showed a different intra-cellular route of the Ab-FZD7 complex compared with sensitive tumors and accumulation of ß-catenin. This coincided with a low sFRP1 and DKK1 (Wnt inhibitors) expression pattern, restored epigenetically with de-methylating agents, and lack of ß-catenin or WTX mutations. The addition of exogenous DKK1 and sFRP1 to the tumor cells enabled the sensitization of FZD7-resistant WT to the FZD7 Ab. Finally, although extremely difficult to achieve because of dynamic cellular localization of FZD7, sorting of FZD7(+) cells from resistant WT, showed them to be highly clonogenic/proliferative, overexpressing WT 'stemness' genes, emphasizing the importance of targeting this fraction. FZD7 Ab therapy alone or in combination with Wnt pathway antagonists may have a significant role in the treatment of WT via targeting of a tumor progenitor population.

Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis.

OBJECTIVE: The central nervous system regulates innate immunity in part via the cholinergic anti-inflammatory pathway, a neural circuit that transmits signals in the vagus nerve that suppress pro-inflammatory cytokine production by an alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) dependent mechanism. Vagus nerve activity is significantly suppressed in patients with autoimmune diseases, including rheumatoid arthritis (RA). It has been suggested that stimulating the cholinergic anti-inflammatory pathway may be beneficial to patients, but it remains theoretically possible that chronic deficiencies in this pathway will render these approaches ineffective. METHODS: Here we addressed the hypothesis that inflammatory cells from RA patients can respond to cholinergic agonists with reduced cytokine production in the setting of reduced vagus nerve activity. RESULTS: Measurement of RR interval variability (heart rate variability, HRV), in RA patients (n = 13) and healthy controls (n = 10) revealed that vagus nerve activity was significantly depressed in patients. Whole blood cultures stimulated by exposure to endotoxin produced significantly less tumour necrosis factor in samples from RA patients as compared to healthy controls. Addition of cholinergic agonists (nicotine and GTS-21) to the stimulated whole blood cultures however significantly suppressed cytokine production to a similar extent in patients and healthy controls. CONCLUSION: These findings suggest that it is possible to pharmacologically target the alpha7nAChR dependent control of cytokine release in RA patients with suppressed vagus nerve activity. As alpha7nAChR agonists ameliorate the clinical course of collagen induced arthritis in animals, it may be possible in the future to explore whether alpha7nAChR agonists can improve clinical activity in RA patients.

Impairments in balance discriminate fallers from non-fallers in COPD.

BACKGROUND: Preliminary evidence suggests individuals with COPD exhibit deficits in balance. Further investigation of balance and risk of falls is warranted in these patients. The objective of this study was to determine the clinical measures that discriminate fallers from non-fallers among patients with COPD. METHODS: A cross-sectional study design was used. Subjects>60 years with COPD attended a single assessment session. A one-year incidence of falls was collected via self-report questionnaire. Risk of falls and balance were determined using the Berg Balance Scale (BBS), Timed Up and Go Test (TUG) and the Activity-Specific Balance Confidence (ABC) Scale. Exercise tolerance was determined from the Six-Minute Walk Test and functional limitation attributable to dyspnea from the Medical Research Council (MRC) dyspnea scale. RESULTS: Of the 39 COPD subjects (FEV(1)=41.5+/-17.0% predicted; age: 71.1+/-6.8 years) who completed the study, 46% (n=18) reported at least one fall in the preceding year. Significant differences between fallers and non-fallers were found for the ABC (65.8+/-18.2 vs. 81.7+/-11.1; p=0.002), TUG (17.0+/-4.9 vs. 14.0+/-3.1s; p=0.024), BBS (45.2+/-5.4 vs. 48.8+/-5.0; p=0.042), use of supplemental oxygen (72% vs. 24%; p=0.002), and MRC dyspnea scale (median 4, range 3 vs. median 3, range 4; p=0.046). CONCLUSIONS: Patients with COPD fall frequently. Standard clinical balance measures discriminate self-reported fallers from non-fallers. These observations draw attention to an important secondary impairment in COPD.

Pulmonary rehabilitation after acute exacerbation of chronic obstructive pulmonary disease in patients who previously completed a pulmonary rehabilitation program.

PURPOSE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) impair health-related quality of life (HRQL). We evaluated the effect of an abbreviated repeat pulmonary rehabilitation (PR) program on HRQL after an AECOPD. METHODS: Patients who had completed PR were followed for up to 12 months to identify an AECOPD and then placed in randomized groups to receive a 3-week repeat-PR intervention or usual care. Measures of HRQL (Chronic Respiratory Disease Questionnaire, CRQ) and functional exercise capacity (6-minute walk distance, 6MWD) were collected at 2 (T(1)), 5 (T(2)), and 12 weeks (T(3)) post-AECOPD. The repeat-PR program was undertaken between T(1) and T(2). Between-group differences were examined using repeated- measures analysis of variance or covariance. RESULTS: Of the 60 patients (30 men, age 69+/-8 years, forced expiratory volume in 1 second 0.86+/-0.40 L, 6MWD 367+/-99 m) followed, 41 experienced an AECOPD 14 +/- 11 weeks after completion of the initial PR program and 33 completed the study. Of these, 16 and 17 were randomized to the intervention and control groups, respectively. No between-group differences were demonstrated at T(2) or T(3). With the exclusion of 5 subjects who experienced a second AECOPD between T(1) and T(3), the participants in the intervention group demonstrated greater reduction in dyspnea when compared to those in the control group at T(3) (0.8+/-1.6 vs -0.4+/-1.3 points per item, P = .04). CONCLUSIONS: The reduction in dyspnea in those who did not experience a second AECOPD provides preliminary evidence for the role of repeat programs. The application of repeat PR should be refined in larger trials.

Anxiety and depression in end-stage COPD.

Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), estimates of their prevalence vary considerably. This probably reflects the variety of scales and methods used to measure such symptoms. Regardless of whether anxiety and depression are considered separately or as a single construct, their impact on COPD patients is important. A heightened experience of dyspnoea is likely to be a contributing factor to anxiety. Feelings of depression may be precipitated by the loss and grief associated with the disability of COPD. Smoking has been associated with nicotine addiction, and the factors that contribute to smoking may also predispose to anxiety and depressive disorders. Randomised controlled trials indicate that exercise training and carefully selected pharmacological therapy are often effective in ameliorating anxiety and depression. Most medical illnesses are influenced by the psychological responses and coping mechanisms that patients use. However, anxiety and depression are associated with dyspnoea, fatigue and altered sleep, all of which also occur in COPD. An understanding of the psychological history and coping mechanisms of patients and the role of anxiety and depressive reactions to illness may enable clinicians to reduce these symptoms and improve quality of life among patients with chronic obstructive pulmonary disease.

Counting, analysing and reporting exacerbations of COPD in randomised controlled trials.

BACKGROUND: Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects. METHODS: Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals. RESULTS: 22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed. CONCLUSIONS: Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review.

BACKGROUND: The widespread application of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function attributable to the programs. OBJECTIVES: To determine the impact of rehabilitation on health-related quality of life (QoL) and exercise capacity in patients with COPD. METHODS: We identified randomized controlled trials (RCTs) from the Cochrane Airways Group Specialised Register. We selected RCTs of rehabilitation in patients with COPD in which quality of life (QoL) and/or exercise capacity were measured. Rehabilitation was defined as exercise training for at least 4 weeks with or without education and/or psychological support. Control groups received conventional community care without rehabilitation. RESULTS: A total of 31 RCTs met the inclusion criteria. We found statistically significant improvements for all the outcomes. In 4 important domains of QoL (Chronic Respiratory Questionnaire scores for Dyspnea, Fatigue, Emotional function and Mastery), the effect was larger than the minimal clinically important difference. For exercise capacity, the effect was small and slightly below the threshold of clinical significance for the six-minute walking distance (WMD: 48 m; 95% CI: 32 to 65; n = 16 trials). CONCLUSIONS: Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.

Oxygen therapy during exercise training in chronic obstructive pulmonary disease.

BACKGROUND: Exercise training within the context of pulmonary rehabilitation improves outcomes of exercise capacity, dyspnea and health-related quality of life in individuals with chronic obstructive pulmonary disease (COPD). Supplemental oxygen in comparison to placebo increases exercise capacity in patients performing single-assessment exercise tests. The addition of supplemental oxygen during exercise training may enable individuals with COPD to tolerate higher levels of activity with less exertional symptoms, ultimately improving quality of life. OBJECTIVES: To determine how supplemental oxygen in comparison to control (compressed air or room air) during the exercise-training component of a pulmonary rehabilitation program affects exercise capacity, dyspnea and health-related quality of life in individuals with COPD. SEARCH STRATEGY: All records in the Cochrane Airways Group Specialized Register of trials coded as 'COPD' were searched using the following terms: (oxygen* or O2*) AND (exercis* or train* or rehabilitat* or fitness* or physical* or activ* or endur* or exert* or walk* or cycle*). Searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE and CINAHL databases identified studies. The last search was carried out in June 2006. SELECTION CRITERIA: Only randomized controlled trials (RCTs) comparing oxygen-supplemented exercise training to non-supplemented exercise training (control group) were considered for inclusion. Participants were 18 years or older, diagnosed with COPD and did not meet criteria for long-term oxygen therapy. No studies with mixed populations (pulmonary fibrosis, cystic fibrosis, etc) were included. Exercise training was greater than or equal to three weeks in duration and included a minimum of two sessions a week. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Missing data were requested from authors of primary studies. MAIN RESULTS: Five RCTs met the inclusion criteria. The maximum number of studies compared in the meta-analysis was three (31 on oxygen versus 32 control participants), because all included studies did not measure the same outcomes. When two studies were pooled, statistically significant improvements of oxygen-supplemented exercise training were found in constant power exercise time, WMD 2.68 minutes (95% CI 0.07 to 5.28 minutes). Supplemental oxygen increased the average exercise time from 6 to 14 minutes; the control intervention increased average exercise time from 6 to 12 minutes. Constant power exercise end-of-test Borg score (on a scale from 1 to 10) also showed statistically significant improvements with oxygen-supplemented exercise training, WMD -1.22 units (95% CI -2.39 to -0.06). One study showed a significant improvement in the change of Borg score after the shuttle walk test, by -1.46 units (95% CI -2.72 to -0.19). There were no significant differences in maximal exercise outcomes, functional exercise outcomes (six-minute walk test), shuttle walk distance, health-related quality of life or oxygenation status. According to the GRADE system most outcomes were rated as low quality because they were limited by study quality. AUTHORS' CONCLUSIONS: This review provides little support for oxygen supplementation during exercise training for individuals with COPD, but the evidence is very limited. Studies with larger number of participants and strong design are required to permit strong conclusions, especially for functional outcomes such as symptom alleviation, health-related quality of life and ambulation.

Perspectives that influence action plans for chronic obstructive pulmonary disease.

BACKGROUND: Prompt treatment of acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) improves quality of life and reduces the use of health care resources. Although patient self-management through an individualized action plan (AP) can help with early initiation of therapy, its use is critically dependent on the patient recognizing the features of an exacerbation. OBJECTIVE: To describe COPD patients' experiences with AEs, as well as health care professionals' (HCPs') attitudes toward the provision of an AP as part of self-management education. METHODS: Thirty-two patients with moderate to severe COPD who recently experienced at least one AE, and 22 HCPs with experience in the management of COPD, were interviewed. RESULTS: The most common symptoms and signs associated with an AE were difficulty breathing (84%), fatigue (81%), cold symptoms (59%), changes in sputum colour (53%) or amount (47%), and cough (44%). The main precipitants identified were environmental triggers (47%), infective agents (31%), excessive activities (25%), emotional factors (16%) and changes in medications (9%). Strategies for dyspnea relief included increasing medications (72%), resting (56%), avoiding exposure to environmental triggers (41%) and performing breathing exercises (31%). Patients supported the use of an AP and recommended that it be individualized for symptoms and triggers, and that it should also include strategies for addressing anxiety and depression. HCPs also supported the use of an individualized AP and recommended that it be regularly revisited, depending on the patient's disease severity. CONCLUSIONS: Patients' experiences with AEs do not always conform to a standard medical definition. Therefore, an understanding of their experience is of value in the design of an individualized AP. HCPs support the use of an AP that emphasizes self-management of exacerbations as well as general COPD management.

Nutritional supplementation for stable chronic obstructive pulmonary disease.

BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomised controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. Searches are current as of March 2004. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: Eleven studies recruiting 352 participants met the inclusion criteria. Eight papers were considered as high quality. Two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. AUTHORS' CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.

The influence of lung volume reduction surgery on exercise in patients with COPD.

Although the influence of lung volume reduction surgery (LVRS) on incremental- and constant-power exercise is important in the evaluation of this procedure for patients with chronic obstructive pulmonary disease (COPD), it is rarely reported even in large randomised controlled trials. This report describes 39 patients with severe COPD ((mean +/- SE) forced expiratory volume in one second 32 +/- 2% pred, functional residual capacity 195 +/- 6% pred) who participated in a randomised controlled trial of LVRS and who completed incremental exercise tests at 6 months as well as endurance tests (constant power of 25 +/- 1 W) at 3, 9 and 12 months. Peak oxygen uptake (V'O2,pk) was similar between the treatment (n = 19) and control groups (n = 20) at baseline. After LVRS, the treatment group had a significantly greater V'O2,pk (mean difference (95% CI) 1.28 (0.07-2.50) mL x kg x min(-1)) and power (13 (6-20) W). The treatment group achieved a significantly greater minute ventilation (7.1 (2.9-11.3) L x min(-1)) with a greater tidal volume (0.16 (0.04-0.28) L). Baseline endurance was similar between groups. After surgery, there were significant between-group differences in endurance time, which were maintained at 12 months (7.3 (3.9-10.8) min). Lung volume reduction surgery is associated with an increase in exercise capacity and endurance, as compared with conventional medical treatment.

Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND: The clinical value of LVRS has been questioned in the absence of trials comparing it with pulmonary rehabilitation, the prevailing standard of care in COPD. Patients with heterogeneous emphysema are more likely to benefit from volume reduction than those with homogeneous disease. Disease specific quality of life is a responsive interpretable outcome that enables health professionals to identify the magnitude of the effect of an intervention across several domains. METHODS: Non-smoking patients aged <75 years with severe COPD (FEV(1) <40% predicted, FEV(1)/FVC <0.7), hyperinflation, and evidence of heterogeneity were randomised to surgical or control groups after pulmonary rehabilitation and monitored at 3 month intervals for 12 months with no crossover between the groups. The primary outcome was disease specific quality of life as measured by the Chronic Respiratory Questionnaire (CRQ). Treatment failure was defined as death or functional decline (fall of 1 unit in any two domains of the CRQ). Secondary outcomes included pulmonary function and exercise capacity. RESULTS: LVRS resulted in significant between group differences in each domain of the CRQ at 12 months (change of 0.5 represents a small but important difference): dyspnoea 1.9 (95% confidence interval (CI) 1.3 to 2.6; p<0.0001); emotional function 1.5 (95% CI 0.9 to 2.1; p<0.0001); fatigue 2.0 (95% CI 1.4 to 2.6; p<0.0001); mastery 1.8 (95% CI 1.2 to 2.5; p<0.0001). In the control group one of 27 patients died and 16 experienced functional decline over 12 months. In the surgical group four of 28 patients died and three experienced functional decline (hazard ratio = 3.1 (95% CI 1.3 to 7.6; p=0.01). Between group improvements (p<0.05) in lung volumes, flow rates, and exercise were sustained at 12 months (RV -47% predicted (95% CI -71 to -23; p=0.0002); FEV(1) 0.3 l (95% CI 0.1 to 0. 5; p=0.0003); submaximal exercise 7.3 min (95% CI 3.9 to 10.8; p<0.0001); 6 minute walk 66 metres (95% CI 32 to 101; p=0.0002). CONCLUSIONS: In COPD patients with heterogeneous emphysema, LVRS resulted in important benefits in disease specific quality of life compared with medical management, which were sustained at 12 months after treatment.

The effect of postrehabilitation programmes among individuals with chronic obstructive pulmonary disease.

The purpose of this study was to examine the effects of two post-rehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). Subjects with COPD (n=109) were randomised to receive either enhanced follow-up (EF) or conventional follow-up (CF). Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint (2 weeks) between their visits. Both groups had scheduled appointments with a physical therapist and physician at 3-monthly intervals after discharge. Longitudinal data were recorded in 85 subjects (37 EF and 48 CF). Over the course of the study, there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction. There was no difference in total chronic respiratory disease questionnaire score between groups at baseline or at any time interval despite a significant difference with time. There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups.