Total St. George's Respiratory Questionnaire Research Articles

Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy. To determine the efficacy of thalidomide in suppressing cough in patients with IPF. 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028) 1 university center. 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods. The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life. CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide. This was a single-center study of short duration and small sample size focused on symptom-specific quality of life. Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results. Celgene Corporation.

Relationship Between Lung Function Impairment and Health-Related Quality of Life in COPD and Interstitial Lung Disease

Health-related quality-of-life (HRQL) measures have been correlated with lung function in patients with COPD and interstitial lung disease (ILD). However, different pathophysiologic mechanisms may influence how these distinct diseases affect HRQL, resulting in differing HRQL by pulmonary diagnosis among patients with similar severity of ventilatory impairment. The National Heart, Lung, and Blood Institute Lung Tissue Research Consortium provided data on well-characterized participants with COPD (n = 576) and ILD (n = 405) at four clinical sites. Using multiple linear regression, we examined the effects of FEV₁ (% predicted) and diagnosis (ILD vs COPD) on HRQL scores, including total St. George Respiratory Questionnaire (SGRQ) scores and Short Form-12 (SF-12) physical component summary (PCS) and mental component summary (MCS) scores. Participants with ILD had, on average, higher SGRQ scores (15.33 points; 95% CI, 12.46-18.19; P <.001) and lower SF-12 PCS scores (-4.73 points; 95% CI, -6.31 to -3.14; P <.001) compared with patients with COPD with similar FEV₁ % predicted values, indicating worse HRQL. The specific diagnosis also modified the effect of FEV₁ on the total SGRQ score (P = .003) and the SF-12 PCS score (P = .03). There was no relationship between lung function and SF-12 MCS scores. HRQL scores were worse for patients with ILD compared with patients with COPD with similar degrees of ventilatory impairment. Differences in dyspnea mechanism or in the rate of disease progression may account for these differences in HRQL.

The effects of Chinese Yam-Epimedium mixture on respiratory function and quality of life in patients with chronic obstructive pulmonary disease

ObjectiveTo examine the clinical effects of a mixture of Chinese Yam and Epimedium in patients with stable moderate or severe chronic obstructive pulmonary disease (COPD). MethodsForty-nine patients with COPD were randomly allocated to a group whose usual treatment was supplemented with oral Chinese Yam-Epimedium mixture, or a control group given placebo. For each patient, body mass index, airflow obstruction, dyspnea, and exercise capacity were measured and converted into the BODE index before treatment and at one and three months after initiation of treatment. Participants also completed the St George's Respiratory Questionnaire (SGRQ) at the same intervals. ResultsAfter one month, improvements were seen in the BODE index and SGRQ of participants taking Chinese Yam-Epimedium mixture compared to controls. There were statistically significant differences in the SGRQ: three of its components and the total SGRQ scores were significantly decreased (P<0.05), respiratory symptom scores had improved (P<0.01), and the dyspnea component of the BODE index had significantly decreased (P<0.05). Similar improvements were observed after three months of treatment, but exercise tolerance had also improved: the six-minute walking distance had significantly increased (P<0.05) in the treatment group when compared with controls. ConclusionChinese Yam-Epimedium mixture can significantly improve dyspnea, exercise capacity, and the quality of life of patients with stable moderate or severe COPD.

Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos

ObjectiveDescribe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite.DesignCross-sectional descriptive.SettingAsbestos-related disease clinic in Libby, Montana USA.Participants329 individuals exposed to LAA; mostly men,...

Exacerbation frequency and course of COPD

BackgroundExacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.MethodsThis retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0–1, >1–2, and >2). Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).ResultsIn total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.ConclusionIncreasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death.

Gender and Health Status Response to Long-Term Oxygen Therapy in COPD Patients

Introduction The association of gender with health status (HS) response to long-term oxygen therapy (LTOT) in very severe COPD is unclear. The aims of this study were: (1) to compare dyspnea perception and HS between male and female with very severe COPD at baseline and (2) to provide a prospective assessment of HS response to LTOT, according to gender. Patients and methods Hypoxemic COPD ( n=97, age: 65.5±9.6 years, 53% males) were enrolled in a prospective longitudinal study over 12 months or until death. St. George's Respiratory Questionnaire (SGRQ) and baseline dyspnea index (BDI) were assessed. Results At baseline, HS impairment and dyspnea sensation were similar between genders. After 12 months of LTOT, women presented improvement in symptom (64.1±20.6 versus 40.6±22.9; P<.0001) and total SGRQ scores. Men also showed improvement in symptoms after 12 months (62.7±23.3 versus 49.6±22.8; P<.0005); however, they presented deterioration of activity, impact, and total scores during the study period, with markedly decline of activity domain (68.5±20.0 versus 75.9±16.9; P=.008). BDI did not show significant difference by gender over the study period. Conclusions Our results show that the HS course in very severe COPD patients differs according to gender, as females show greater response longitudinally to LTOT.

Predicting EQ-5D Values Using the SGRQ

Objectives The purpose of this study was to develop and validate an algorithm that predicts EQ-5D utility from the St. George's Respiratory Questionnaire (SGRQ) in subjects with chronic obstructive pulmonary disease and to examine the effect of using this algorithm in predicting quality-adjusted life-years (QALYs). Methods In the TORCH (Towards a Revolution in COPD Health) trial, the SGRQ and EQ-5D were administered at baseline and every 24 weeks for 3 years. To map EQ-5D utility from the SGRQ, ordinary least squares (OLS), generalized linear models (GLMs) and two-part models were used. Algorithms were developed in a fitting sample and used to predict utility scores in a validation sample and selected based on root-mean-square error (RMSE). QALYs were estimated from the algorithm and compared to QALYs derived from EQ-5D utility scores collected in the trial. Results A simple OLS algorithm was found to perform as well as algorithms developed using more complex modeling structures. The resulting model was (RMSE 0.1723): EQ-5D = 0.9617 − 0.0013 × SGRQ total − 0.0001 × SGRQ total 2 + 0.0231 × male. Ordering of treatments by QALY gain was dependent on the method of utility estimation. Conclusion A mapping algorithm can be used to predict EQ-5D utility scores from the SGRQ and may be useful in some situations; however, for use in a health technology assessment (HTA) submission in which precision of estimation is important, it is in the interests of both the manufacturer and the HTA body that utility scores be directly derived from the clinical trial population.

Pulmonary rehabilitation improves exercise capacity and quality of life in underweight patients with chronic obstructive pulmonary disease

An estimated 20-40% of COPD patients are underweight. We sought to confirm the physiological and psychosocial benefits of pulmonary rehabilitation programmes (PRP) in underweight compared with non-underweight patients with COPD. Twenty-two underweight COPD patients with BMI <20 kg/m(2), and 22 non-underweight COPD patients, who were matched for FEV(1) and age, were studied. All patients had moderate-to-very severe COPD. All patients participated in 12-week, hospital-based outpatient PRP consisting of two sessions per week. Baseline and post-PRP status were evaluated by spirometry, cardiopulmonary exercise testing, ventilatory muscle strength and the St. George's Respiratory Questionnaire (SGRQ). At baseline, the age distribution and airflow obstruction were similar in underweight and non-underweight patients with COPD. Baseline exercise capacity, inspiratory muscle strength and SGRQ total and symptoms scores were significantly lower in the underweight patients (all P < 0.05). After the PRP, there was significant weight gain in the underweight COPD patients (mean increase 0.8 kg, P = 0.01). There were also significant improvements in peak oxygen uptake, peak workload and the SGRQ total, symptoms, activity and impact scores in both underweight and non-underweight patients with COPD (all P < 0.05). Underweight patients with COPD have impaired exercise capacity and health-related quality of life (HRQL). Exercise training with supplemental oxygen may result in significant weight gains and improvements in exercise capacity and HRQL. Exercise training is indicated for underweight patients with COPD.

Risk factors for readmission after hospital discharge in chronic obstructive pulmonary disease. The role of quality of life indicators

AimsTo identify demographic, clinical, functional and inherent quality of life (QOL) and depression factors with impact on use of the Emergency Services (ES) or readmission after hospital discharge for acute exacerbation of chronic obstructive pulmonary disease (COPD) over a period of 66 weeks. QOL was evaluated by the St. George's Respiratory Questionnaire (SGRQ). The Beck Depression Inventory assessed depression.We prospectively evaluated 45 patients (84.4% male, median age 73 years, stage IV 51%). The median total SGRQ score was 50.6, with a greater impact on symptoms, especially in younger patients (r=-0.425; p=0.043), and activity limitation than emotional impact of the disease. More than half were depressed. Worse QOL meant depression (R=0.699; p=0.02). Low FEV1 correlated with depression (r=-0.46; p =0.05) but not with QOL. Long-acting anti-cholinergic bronchodilator and inhaled steroids improved QOL. Almost 85% of patients used ES (25.8% for exacerbated COPD). Rate of hospital readmission for all reasons and exacerbated COPD was 64.9% and 33.3%. The number of readmissions (all reasons) was correlated with age (R=0.48; p=0003), cor pulmonale (R=-0.46; p=0.03) and QOL (R=0.67; p=0.004). Depressed patients (R=0.51; p=004), with low FEV1 (R=-0413; p=0.04) and with cor pulmonale (R=-046, p=0.005) had more inhospital days for exacerbation of COPD.QOL and depression are variables to consider in the evaluation and treatment of patients with COPD as part of a set of clinical and functional data that can predict the risk of readmission after hospital discharge for exacerbated COPD.

Risco de reinternamento na doença pulmonar obstrutiva crónica – Estudo prospectivo com ênfase no valor da avaliação da qualidade de vida e depressão

Aims: To identify demographic, clinical, functional and inherent quality of life (QOL) and depression factors with impact on use of the Emergency Services (ES) or readmission after hospital discharge for acute exacerbation of chronic obstructive pulmonary disease (COPD) over a period of 66 weeks. QOL was evaluated by the St. George’s Respiratory Questionnaire (SGRQ). The Beck Depression Inventory assessed depression.We prospectively evaluated 45 patients (84.4% male, median age 73 years, stage IV 51%). The median total SGRQ score was 50.6, with a greater impact on symptoms, especially in younger patients (r=-0.425; p=0.043), and activity limitation than emotional impact of the disease. More than half were depressed. Worse QOL meant depression (R=0.699; p=0.02). Low FEV1 correlated with depression (r=-0.46; p =0.05) but not with QOL. Long-acting anti-cholinergic bronchodilator and inhaled steroids improved QOL. Almost 85% of patients used ES (25.8% for exacerbated COPD). Rate of hospital readmission for all reasons and exacerbated COPD was 64.9% and 33.3%. The number of readmissions (all reasons) was correlated with age (R=0.48; p=0003), cor pulmonale (R=-0.46; p=0.03) and QOL (R=0.67; p=0.004). Depressed patients (R=0.51; p=004), with low FEV1 (R=-0413; p=0.04) and with cor pulmonale (R=-046, p=0.005) had more inhospital days for exacerbation of COPD.QOL and depression are variables to consider in the evaluation and treatment of patients with COPD as part of a set of clinical and functional data that can predict the risk of readmission after hospital discharge for exacerbated COPD.Rev Port Pneumol 2010; XVI (5): 759-777

The Effects of Asthma Education on Asthma Knowledge and Health-Related Quality of Life in Taiwanese Asthma Patients

Patient education is a critical component of asthma management. Limited data from longitudinal research studies are available from Taiwan to show the effect of asthma education on knowledge and health-related quality of life (HRQOL) in asthma patients. This study was designed to determine the effectiveness of an asthma education program on asthma general knowledge and HRQOL in Taiwanese patients with asthma during a 6-month follow-up period. One hundred eighteen patients were recruited using purposive sampling, 42 of whom were enrolled in an asthma education program and 76 of whom received routine care. Measurements were completed at baseline and at 1, 3, and 6 months after enrollment. Over the 6 months of follow-up, asthma knowledge was measured using the Chinese language version of the asthma general knowledge questionnaire for adults, whereas HRQOL was measured using the St. George's Respiratory Questionnaire (SGRQ). Asthma knowledge increased significantly in the intervention group as compared with the comparison group (p < .001), and Group x Month interaction effects were found. Total SGRQ mean score and the three subscales showed no significant differences between intervention and comparison groups. However, overall SGRQ trends and subscale scores for both groups decreased significantly through the first, third, and sixth months. We observed an increase in asthma general knowledge but no significant improvement in HRQOL using an asthma structured-education program.

A randomised controlled equivalence trial to determine the effectiveness and cost–utility of manual chest physiotherapy techniques in the management of exacerbations of chronic obstructive pulmonary disease (MATREX)

To estimate the effect, if any, of manual chest physiotherapy (MCP) administered to patients hospitalised with chronic obstructive pulmonary disease (COPD) exacerbation on both disease-specific and generic health-related quality of life. To compare the health service costs for those receiving and not receiving MCP. A pragmatic, randomised controlled trial powered for equivalence. It was not possible to blind participants, clinicians or research staff to study arm allocation during the intervention. Four UK hospitals in Norwich, Great Yarmouth, King's Lynn and Liverpool. 526 participants aged 34-91 years were recruited between November 2005 and April 2008; of these, 372 provided evaluable data for the primary outcome. All persons hospitalised with COPD exacerbation and evidence of sputum production on examination were eligible for the trial providing there were no contraindications to performing MCP. Participants were allocated to either MCP or no MCP on an intention-to-treat (ITT) basis. However, active cycle of breathing techniques (ACBT) was used in both arms. Participants allocated to the intervention were guided to perform ACBT while the physiotherapist delivered MCP. Participants allocated to the control arm received instruction on ACBT only. The primary outcome was COPD-specific quality of life, measured using the St George's Respiratory Questionnaire (SGRQ) at 6 months post randomisation. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to calculate the quality-adjusted life-year (QALY) gain associated with MCP compared with no MCP. Secondary physiological outcome measures were also used. Of the 526 participants, 261 were allocated to MCP and 264 to control, with 186 participants evaluable in each arm. ITT analyses indicated no significant difference at 6 months post randomisation in total SGRQ score [adjusted effect size (no MCP - MCP) 0.03 (95% confidence interval, CI -0.14 to 0.19)], SGRQ symptom score [adjusted effect size 0.04 (95% CI -0.15 to 0.23)], SGRQ activity score [adjusted effect size -0.02 (95% CI -0.20 to 0.16)] or SGRQ impact score [adjusted effect size 0.02 (95% CI -0.15 to 0.18)]. The imputed ITT and per-protocol results were similar. No significant differences were observed in any of the outcome measures or subgroup analyses. Compared with no MCP, employing MCP was associated with a slight loss in quality of life (0.001 QALY loss) but lower health service costs (cost saving of 410.79 pounds). Based on these estimates, at a cost-effectiveness threshold of lambda = 20,000 pounds per QALY, MCP would constitute a cost-effective use of resources (net benefit = 376.14 pounds). There was, however, a high level of uncertainty associated with these results and it is possible that the lower health service costs could have been due to other factors. In terms of longer-term quality of life the use of MCP did not appear to affect outcome. However, this does not mean that MCP is of no therapeutic value to patients with COPD in specific circumstances. Although the cost-effectiveness analysis suggested that its use was cost-effective, much uncertainty was associated with this finding and it would be difficult to justify providing MCP therapy on the basis of cost-effectiveness alone. Future research should include evaluation of MCP for patients with COPD producing high volumes of sputum, and an evaluation of the effectiveness of ACBT in COPD exacerbation. Current Controlled Trials ISRCTN13825248.

Nebulized formoterol provides added benefits to tiotropium treatment in chronic obstructive pulmonary disease

The use of one or more long-acting bronchodilators is key in the maintenance therapy of chronic obstructive pulmonary disease (COPD). This analysis pooled the results of two double-blind studies evaluating the efficacy and safety of adding nebulized formoterol fumarate inhalation solution (FFIS) to maintenance tiotropium (TIO) treatment. Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ). The mean standardized area under the curve for FEV(1) over 3 hours (FEV(1)AUC(0-3)), the primary efficacy variable, was significantly higher in the FFIS/TIO group than the PLA/TIO group on day 1 (140 mL difference, P<0.0001) and week 6 (192 mL difference, P<0.0001). Mean TDI scores in the FFIS/TIO and PLA/TIO groups were 1.97 and 0.67, respectively (P=0.0001). Mean albuterol use declined in the FFIS/TIO group from 2.6 to 1.5 puffs/day compared with little change in the PLA/TIO group (P<0.0001). SGRQ scores were similar between treatment groups with the exception of the symptoms score, which improved in the FFIS/TIO group (-5.8) compared with PLA/TIO (-1.0), and more FFIS/TIO-treated subjects experienced a clinically significant improvement in total SGRQ score. More PLA/TIO-treated subjects than FFIS/TIO-treated subjects experienced adverse events (AEs) (45.7% vs. 31.0%) and COPD exacerbations (7.9% vs. 3.4%). The addition of FFIS to maintenance TIO treatment for moderate to severe COPD results in significantly improved FEV(1) and dyspnea, decreased rescue medication use, and a lower incidence of AEs and COPD exacerbations. The addition of FFIS to TIO yields clinically and statistically significant benefits for COPD patients and might be of long-term benefit.

Maintaining benefits following pulmonary rehabilitation: a randomised controlled trial

The aim of this study was to determine if weekly, supervised, outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than standard care of unsupervised home exercise training. Chronic obstructive pulmonary disease (COPD) subjects completed an 8-week pulmonary rehabilitation programme, were randomised to an intervention group (IG) of weekly, supervised, exercise plus home exercise or to a control group (CG) of unsupervised home exercise and followed for 12 months. Outcome measurements at baseline (after pulmonary rehabilitation), and 3, 6 and 12 months included the 6-min walk test and St George's Respiratory Questionnaire (SGRQ). 59 subjects with moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage II) were recruited and 48 subjects completed the study. 12-month mean difference showed no significant change from baseline in 6-min walk distance (IG -11 m, 95% CI -21-10 m; CG -6 m, 95% CI -34-11 m) or total SGRQ score (IG 3, 95% CI -0.8-7; CG -3, 95% CI -7-3). 12 months following pulmonary rehabilitation both weekly, supervised, outpatient-based exercise plus unsupervised home exercise and standard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD.

Characteristics of patients admitted for the first time for COPD exacerbation

This study describes the characteristics of a large sample of patients hospitalised for the first time for a chronic obstructive pulmonary disease (COPD) exacerbation. All subjects first admitted for a COPD exacerbation to nine teaching Spanish hospitals during January 2004-March 2006, were eligible. COPD diagnosis was confirmed by spirometry under stability. At admission, sociodemographic data, lifestyle, previous treatment and diagnosis of respiratory disease, lung function and Charlson index of co-morbidity were collected. A comprehensive assessment, including dyspnea, lung function, six-minute walking test, and St. George's Respiratory Questionnaire (SGRQ), was completed 3 months after admission, during a clinically stable disease period. Three-hundred and forty-two patients (57% of the eligible) participated in the study: 93% males, mean (SD) age 68 (9) years, 42% current smokers, 50% two or more co-morbidities, 54% mild-to-moderate dyspnea, post-bronchodilator FEV(1) 52 (16)% of predicted (54% mild-to-moderate COPD in ATS/ERS stages), 6-min walking distance 440 m, total SGRQ score 37 (18), and 36% not report respiratory disease. The absence of a previous COPD diagnosis, positive bronchodilator test, female gender, older age, higher DLco and higher BMI were independently associated with less severe COPD. We show that the patients admitted after presenting with their first COPD exacerbation have a wide range of severity, with a large proportion of patients in the less advanced COPD stages.

Effects of a Disease Management Program in Individuals with Alpha-1 Antitrypsin Deficiency

Disease management programs improve outcomes in subjects with chronic obstructive pulmonary disease (COPD), but their effect in subjects with alpha-1 antitrypsin deficiency (AATD) has not been evaluated. To assess the impact of a disease management program, applicable to subjects with AATD-associated COPD throughout the United States, on exacerbations, healthcare resource utilization and health-related quality of life (HRQoL). The Alpha-1 Disease Management and Prevention Program (ADMAPP) consisted of comprehensive written educational patient-directed material for self-study and treatment plans. Program reinforcement was performed through monthly phone calls by specialized coordinators. Outcomes were collected prospectively for 12 months before, and 12 months after enrollment into the program. Exacerbations and healthcare resource utilization were recorded monthly. HRQoL was measured with the St George's Respiratory Questionnaire (SGRQ) every 6 months and the Short Form-36 (SF-36) every 12 months. A total of 878 subjects completed the 2-year study. During the intervention year, there was a significant increase in the use of long-acting bronchodilators, better compliance with oxygen therapy, and more use of steroid courses during exacerbations. Total exacerbation rates, unscheduled physician visits and emergency room visits significantly decreased. There was also a statistically significant slowing in the deterioration of the SGRQ's activity domain, while total SGRQ scores remained stable during the study. Significant improvements were observed in some of the SF-36 domains, particularly in the general health domain. The ADMAPP improved health outcomes in subjects with AATD-associated COPD.

Breathing and relaxation training improves respiratory symptoms and quality of life in asthmatic adults

Does breathing and relaxation training improve respiratory symptoms and quality of life in adults with asthma? Randomised controlled trial. Primary care (GP practice) in Hertfordshire, UK. Adults diagnosed with asthma and registered with the GP practice were recruited via a postal survey and invited to attend for a physiotherapy assessment of their asthma; 85 met the inclusion criteria (age 16–70 years, proficient in English, no serious co-morbidity) and agreed to participate in the trial. They were randomised to the intervention (n = 39) or control (n = 46) group. Both groups received usual medical care. The intervention group received 5 × 60-minute sessions of individual treatment by the Papworth method. The method involves relaxation training, teaching of appropriate tidal and minute volumes for current metabolic activity, minimisation of inappropriate use of accessory muscles, diaphragmatic breathing, nasal breathing, and integration of these techniques into activities of daily living. Assessments were undertaken at baseline, post-treatment (6 months after baseline), and at 12 months. The primary outcome measure was the St. George's Respiratory Questionnaire (SGRQ). Secondary outcome measures were the Hospital Anxiety and Depression Scale (HADS), the Nijmegen hyperventilation questionnaire, resting respiratory rate and end-tidal carbon dioxide level, and spirometry. Post-treatment and 12-month data were available for 78 and 72 patients respectively. Post treatment, the Symptoms subscale of the SGRQ was significantly better in the intervention group (by 11 points, 95% CI 2 to 20). This treatment effect was still present at 12 months (by 9 points, 95% CI 1 to 17). The other subscales of the SGRQ (Activities, Impacts) did not show a significant treatment effect, but the total SGRQ score was significantly better in the intervention group at 12 months, after adjustment for baseline values ( p = 0.05). Nijmegen scores were significantly better in the intervention group at post-treatment (by 4 points, 95% CI 0 to 8), and at 12 months after adjustment for baseline values ( p = 0.01). The only other significant differences in the remaining secondary outcomes were a reduction in relaxed breathing rate for the intervention group post treatment (by 5 breaths per minute, 95% CI 4 to 7), and at 12 months (by 6 breaths per minute, 95% CI 4 to 7). This study supports the hypothesis that the Papworth method ameliorates respiratory symptoms, reduces ventilation rate and improves quality of life in a general practice population of adults diagnosed with asthma.

The Efficacy and Safety of Cilomilast in COPD

The aim of this review is to present the clinical data on the efficacy and safety of cilomilast in patients with chronic obstructive pulmonary disease (COPD). Over 6000 COPD patients received cilomilast during an extensive clinical development programme performed by GlaxoSmithKline (GSK).Five phase III randomized, double-blind, placebo-controlled, parallel-group pivotal studies were conducted in poorly reversible patients (<15% or <200 mL improvement over baseline in forced expiratory volume in 1 second (FEV(1)) after salbutamol). Patients were randomized to receive oral cilomilast 15 mg (n = 2088) or placebo (n = 1408) twice daily for 24 weeks. The co-primary efficacy variables were changes from baseline in trough (predose) FEV(1) and in total score of the St George's Respiratory Questionnaire (SGRQ).Additional studies were performed to investigate the anti-inflammatory actions of cilomilast by measuring inflammatory cells and mediators in biopsies and induced sputum; to assess the long-term effects of cilomilast; to assess the cardiac safety of cilomilast; and to assess the efficacy of cilomilast on hyperinflation. Results from one of the phase III and from one supportive study have been previously published.In the phase III pivotal studies, when averaged over 24 weeks, the mean change from baseline in FEV(1) in the cilomilast group showed improvement compared with placebo in all studies (range 24-44 mL treatment difference). When averaged over 24 weeks, there was a similar improvement in the mean total SGRQ score in both treatment groups with a decrease ranging from -1.8 to -4.2 units in the cilomilast group and 0.4 to -4.9 units in the placebo group. Only one study, however, showed both a statistically and clinically meaningful difference between the two treatment groups (treatment difference -4.1 units; p < 0.001). Although cilomilast was shown to reduce COPD exacerbations in some of these studies, there was no effect on the incidence of COPD exacerbations in a study specifically powered to detect a difference compared with placebo.No significant change was found in the primary endpoints of the anti-inflammatory studies, although some anti-inflammatory activity was detected, including a reduction in tissue CD8+ T lymphocytes and CD68+ macrophages in airway biopsies. In addition, studies did not demonstrate a consistent significant effect of cilomilast on hyperinflation.In all studies, adverse events associated with the gastrointestinal body system were reported more frequently in the cilomilast group than the placebo group and predominantly occurred within the first 2 weeks of initiating cilomilast therapy.During the cilomilast development programme a number of different endpoints were investigated to characterize the efficacy and safety of this second-generation phosphodiesterase 4 inhibitor. Safety assessments throughout the late-phase programme did not reveal any evidence of serious safety concerns with the use of cilomilast. Previous studies in phase II and early phase III had shown improvements in efficacy endpoints and some evidence of an anti-inflammatory mechanism of action. However, subsequent phase III studies failed to definitively confirm the earlier programme results, which led to termination of the development of cilomilast.

Efficacy and safety of formoterol fumarate delivered by nebulization to COPD patients

Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery, particularly for COPD patients unable to use hand-held devices easily or correctly. The long-acting beta2-agonist, formoterol fumarate, is differentiated by its onset of significant bronchodilation within 5 min of administration. In a randomized, double-blind, double-dummy trial, COPD subjects (n=351, mean forced expiratory volume FEV1=1.3 L, 44% predicted) received nebulized formoterol fumarate (Perforomist inhalation solution; FFIS 20 microg) or DPI (Foradil Aerolizer; FA 12 microg), or placebo twice daily for 12 weeks. Efficacy was assessed with 12-h pulmonary function tests, and quality of life was assessed before and after treatment with the St. George's Respiratory Questionnaire (SGRQ). At the 12-week endpoint, FFIS significantly increased FEV1 AUC0-12h relative to placebo (p<0.0001). No evidence of tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment. FFIS also significantly increased peak FEV1, trough FEV1, and standardized FVC AUC0-12h compared with placebo. SGRQ assessment at Week 12 demonstrated significant and clinically meaningful improvements in total score (FFIS vs placebo, -4.9, p=0.0067), symptom, and impact scores. No significant differences in efficacy were observed between the two active treatments. Drug related AEs in the FFIS arm with a frequency > or = 1% and exceeding placebo were dry mouth, nausea, and insomnia. Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated. The efficacy and safety profile of FFIS was comparable to FA DPI.

The Efficacy and Safety of Combination Salmeterol (50 μg)/Fluticasone Propionate (500 μg) Inhalation Twice Daily Via Accuhaler in Chinese Patients With COPD

Few studies of the efficacy and safety of therapy with combinations of salmeterol/fluticasone propionate (SFCs) have been conducted in Chinese patients with COPD, and the benefits of combination therapy in nonsmoking patients with COPD are, to our knowledge, not known. The aims were to establish the efficacy and tolerability of the therapy with SFC (salmeterol, 50 microg/fluticasone, 500 microg, twice daily) in the management of Chinese COPD patients and to investigate the effectiveness of SFC in nonsmokers with COPD. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Changes in prebronchodilator and postbronchodilator FEV(1), quality of life determined by the St. George Respiratory Questionnaire (SGRQ) scores, relief bronchodilator use, nighttime awakenings, and frequency of exacerbations of COPD were measured in patients randomized to receive SFC (n = 297) or placebo (n = 148). Never-smokers, former smokers, and current smokers accounted for 11.7%, 66.7%, and 21.6%, respectively, of the study population. After 24 weeks, the mean changes in prebronchodilator and postbronchodilator FEV(1) were 180 mL (95% confidence interval [CI], approximately 91 to 268; p < 0.001) and 65 mL (95% CI, approximately 14 to 115; p = 0.012), respectively, greater for the SFC group than that for the placebo group. The differences in response to treatment were significant (all p < 0.0001) in former or current smokers but not in never-smokers (p > 0.05). The mean improvement in the total SGRQ score for the SFC group was 5.74 (p < 0.01) greater than that for the placebo group. SFC significantly reduced the frequency of nighttime awakenings and the use of relief bronchodilator. The adjusted ratio of exacerbations of COPD for the SFC group relative to the placebo group was 0.61 (95% CI, approximately 0.45 to 0.84; p < 0.01). There were no significant differences between the SFC and placebo groups in safety measures. SFC therapy achieved sustained improvement in lung function, quality of life, and control of symptoms, and was well tolerated in Chinese patients. Greater improvements in lung function were found only for COPD patients with a history of smoking. http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/studylist.asp Identifier: No. SCO100540.