Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD.

BACKGROUND: Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters. METHODS: Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR. RESULTS: Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state. CONCLUSION: Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.

Misspecification of at-risk periods and distributional assumptions in estimating COPD exacerbation rates: The resultant bias in treatment effect estimation.

In trials comparing the rate of chronic obstructive pulmonary disease exacerbation between treatment arms, the rate is typically calculated on the basis of the whole of each patient's follow-up period. However, the true time a patient is at risk should exclude periods in which an exacerbation episode is occurring, because a patient cannot be at risk of another exacerbation episode until recovered. We used data from two chronic obstructive pulmonary disease randomized controlled trials and compared treatment effect estimates and confidence intervals when using two different definitions of the at-risk period. Using a simulation study we examined the bias in the estimated treatment effect and the coverage of the confidence interval, using these two definitions of the at-risk period. We investigated how the sample size required for a given power changes on the basis of the definition of at-risk period used. Our results showed that treatment efficacy is underestimated when the at-risk period does not take account of exacerbation duration, and the power to detect a statistically significant result is slightly diminished. Correspondingly, using the correct at-risk period, some modest savings in required sample size can be achieved. Using the proposed at-risk period that excludes recovery times requires formal definitions of the beginning and end of an exacerbation episode, and we recommend these be always predefined in a trial protocol.

Global health impacts of ambient fine particulate pollution associated with climate variability.

Air pollution is a key global environmental problem raising human health concern. It is essential to comprehensively assess the long-term characteristics of air pollution and the resultant health impacts. We first assessed the global trends of fine particulate matter (PM2.5) during 1980-2020 using a monthly global PM2.5 reanalysis dataset, and evaluated their association with three types of climate variability including El Niño-Southern Oscillation, Indian Ocean Dipole and North Atlantic Oscillation. We then estimated PM2.5-attributable premature deaths using integrated exposure-response functions. Results show a significant increasing trend of ambient PM2.5 during 1980-2020 due to increases in anthropogenic emissions. Ambient PM2.5 caused a total of âˆ¼ 135 million premature deaths globally during the four decades. Occurrence of air pollution episodes was strongly associated with climate variability, which were associated with up to 14 % increase in annual global PM2.5-attributable premature deaths.

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

Predictive accuracy of patient-reported exacerbation frequency in COPD.

Chronic obstructive pulmonary disease (COPD) exacerbation frequency is important for clinical risk assessment and trial recruitment. In order to accurately establish exacerbation frequency, patients need to be followed for 1 yr, although this is not always practical. 1) Patient recall of exacerbation number during the year prior to recruitment to the London COPD cohort was compared with the number of exacerbations recorded on diary cards during the subsequent year; and 2) patient recall of their exacerbation number after 1 yr of follow-up was compared with documented exacerbations over the same year. A total of 267 patients (forced expiratory volume in 1 s 1.14 L) recorded worsening of respiratory symptoms on daily diary cards for 1 yr. Exacerbations were defined according to previously validated criteria. There was no difference between the exacerbation number recalled by patients prior to recruitment and the number detected during the first year (median 2.0 (interquartile range 1.0-4.0) and 2.0 (1.0-4.0); expected agreement 76.4%; agreement 84.6%; κ = 0.3469). There was no difference between the number of exacerbations remembered by patients and the number recorded on diary cards over the same 1-yr period (2.0 (1.0-4.0) for both groups; expected agreement 74.9%; actual agreement 93.3%; κ = 0.6146). Patients remember the number of exacerbations they have in a year. Accuracy is increased when comparing the same 1-yr period. Patient recall is sufficiently robust for stratification into frequent and infrequent exacerbator groups for subsequent years.

Defective macrophage phagocytosis of bacteria in COPD.

Exacerbations of chronic obstructive pulmonary disease (COPD) are an increasing cause of hospitalisations and are associated with accelerated progression of airflow obstruction. Approximately half of COPD exacerbations are associated with bacteria and many patients have lower airways colonisation. This suggests that bacterial infection in COPD could be due to reduced pathogen removal. This study investigated whether bacterial clearance by macrophages is defective in COPD. Phagocytosis of fluorescently labelled polystyrene beads and Haemophillus influenzae and Streptococcus pneumoniae by alveolar macrophages and monocyte-derived macrophages (MDM) was assessed by fluorimetry and flow cytometry. Receptor expression was measured by flow cytometry. Alveolar macrophages and MDM phagocytosed polystyrene beads similarly. There was no difference in phagocytosis of beads by MDM from COPD patients compared with cells from smokers and nonsmokers. MDM from COPD patients showed reduced phagocytic responses to S. pneumoniae and H. influenzae compared with nonsmokers and smokers. This was not associated with alterations in cell surface receptor expression of toll-like receptor (TLR)2, TLR4, macrophage receptor with collagenous structure, cluster of differentiation (CD)163, CD36 or mannose receptor. Budesonide, formoterol or azithromycin did not suppress phagocytosis suggesting that reduced responses in COPD MDM were not due to medications. COPD macrophage innate responses are suppressed and may lead to bacterial colonisation and increased exacerbation frequency.

Relationship between depression and exacerbations in COPD.

Chronic obstructive pulmonary disease is associated with exacerbations. Some patients are prone to frequent exacerbations and these individuals have a worse quality of life, greater limitation of their daily activity and faster disease progression than patients with less frequent exacerbations. A prospective study in a well-characterised cohort was performed and it was assessed whether depression, as determined by the Centre for Epidemiologic Studies Depression Scale, was related to exacerbation frequency, systemic inflammation and various social factors. The associations of any increase in depressive symptoms at exacerbation were also investigated. Frequent exacerbators had a significantly higher median (interquartile range) baseline depression score than infrequent exacerbators (17.0 (7.0-25.0) and 12.0 (6.0-18.0), respectively). Depressed patients spend significantly less time outdoors and had significantly worse quality of life as measured by the St George's Respiratory Questionnaire. Depression increased significantly in patients from baseline to exacerbation (12.5 (5.0-19.0) and 19.5 (12.0-28.0) respectively). The present study is the first to show a relationship between depression and exacerbation frequency in patients with chronic obstructive pulmonary disease. The finding that frequent exacerbators are more depressed than infrequent exacerbators is relevant, as exacerbation frequency is an important outcome measure in chronic obstructive pulmonary disease.

Outcomes for COPD pharmacological trials: from lung function to biomarkers.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Obstructive lung disease in acute medical patients.

OBJECTIVES: To determine the proportion of adult medical patients who have chronic obstructive pulmonary disease (COPD), using the Global initiative for Chronic Obstructive Lung Disease guidelines (GOLD), and its relation to vascular disease. METHODS: This is a prospective cross-sectional study of adult patients admitted to acute medical wards. Interviewer administered questionnaire, anthropometric and spirometric measurements were done. RESULTS: Spirometry was performed in 720 acute admissions [Mean (SD) age 50.0 (18.9) years, FEV1: 1.98 L (0.83), FEV1/FVC%: 75.1 (11.9)%; males 332 (46.1%), smokers 318 (44%); 43.2% had vascular disease]. Sixty-seven per cent of patients (480) had no airway disease including 35 (4.5%) with chronic cough and sputum with normal spirometry; 89 (12.4%) had asthma and 151 (20.9%) had COPD. Patients with COPD were significantly older [60.3 (16.6) years] than non-COPD patients [47.3 (18.5) years], p < 0.001 and had a greater number of pack years of smoking. A greater percentage of patients with COPD had vascular disease (52%) than the non-COPD patients (40.1%), p = 0.017). Multivariate analysis with vascular disease as outcome variable revealed relationships with older age (p < 0.001) and Indo-Trinidadian ethnicity (p = 0.015), but not with gender (p = 0.321) and smoking (p = 0.442). FEV1% as well as FEV1 showed a significant inverse relationship with vascular disease (p < 0.05). CONCLUSIONS: The prevalence of COPD using GOLD guidelines in acute hospital admissions is 20.9%; 11.7% of admissions have chronic sputum or cough with normal spirometry. Vascular disease is more prevalent in those with COPD. Patients admitted to acute medical care with vascular disease may also have COPD.

MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation.

BACKGROUND: Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood. This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation. METHODS: Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to 1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand. RESULTS: MMP-9 levels increased from 10.5 microg/g [1.2 to 21.1] prior to exacerbation to 17.1 microg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 microg/g [0.6 to 7.8] to 1.5 microg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01). CONCLUSION: During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.

Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been shown to be effective in chronic obstructive pulmonary disease patients with acute respiratory failure. However, its role in patients with severe acute asthma is uncertain. The pathophysiologic condition of acute respiratory failure in asthma is in many ways similar to that of acute respiratory failure in COPD. Therefore, there is reason to believe that NPPV could also be successful in patients with severe acute asthma. OBJECTIVES: To determine the efficacy of NPPV in adults with severe acute asthma in comparison to usual medical care with respect to mortality, tracheal intubation, changes in blood gases and hospital length of stay. SEARCH STRATEGY: An initial search for studies was carried out using CENTRAL. Additional searches were also carried out on MEDLINE, EMBASE, CINAHL, Science Citation, web based clinical trials databases and key journals with web sites were also searched as well as respiratory conference proceedings. Following this, the bibliographies of each randomised controlled trial obtained (and any review articles) was searched for additional studies. Date of most recent search for trials was conducted on May 2004. SELECTION CRITERIA: Only RCTs in adults patients with severe acute asthma were considered for inclusion. Studies including patients with features of COPD were excluded unless data was provided separately for patients with asthma in studies recruiting both COPD and asthma patients. DATA COLLECTION AND ANALYSIS: All data was analysed using RevMan. For continuous variables, a weighted mean difference and 95% confidence interval (95%CI) was calculated for each study outcome. For dichotomous variables relative risk with 95% confidence interval was calculated. MAIN RESULTS: From an initial search of 696 abstracts, 11 trials were obtained in full-text for closer examination. Ten trials were excluded and one included. The one included trial, on 30 patients, showed benefit with NPPV when compared to usual medical care alone with significant improvements in hospitalisation rate, number of patients discharged from emergency department, percent predicted FEV(1), FVC, PEFR and respiratory rate. AUTHORS' CONCLUSIONS: The application of NPPV in patients suffering from status asthmaticus, despite some interesting and very promising preliminary results, still remains controversial. Large, prospective, randomised controlled trials are therefore needed to determine the role of NPPV in status asthmaticus.

Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been shown to be effective in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure. However, its role in patients with severe acute asthma is uncertain. The pathophysiologic condition of acute respiratory failure in asthma is in many ways similar to that of acute respiratory failure in COPD. Therefore, there is reason to believe that NPPV could also be successful in patients with severe acute asthma. OBJECTIVES: To determine the efficacy of NPPV in adults with severe acute asthma, in comparison to usual medical care, with respect to mortality, tracheal intubation, changes in blood gases, and hospital length of stay. SEARCH STRATEGY: An initial search for studies was carried out using the Cochrane Controlled Trials Register (CENTRAL). Additional searches were carried out on MEDLINE, EMBASE, CINAHL, Science Citation and web based clinical trials databases. Key journals with web sites were also searched as well as respiratory conference proceedings. Following this, the bibliographies of each randomised controlled trial obtained (and any review articles) were searched for additional studies. The date of the most recent search for trials was May 2004. SELECTION CRITERIA: All data were analysed using RevMan. For continuous variables a weighted mean difference and 95% confidence interval (95% CI) was calculated for each study outcome. For dichotomous variables relative risk with 95% confidence interval was calculated. DATA COLLECTION AND ANALYSIS: All data was analysed using RevMan. For continuous variables, a weighted mean difference and 95% confidence interval (95%CI) was calculated for each study outcome. For dichotomous variables relative risk with 95% confidence interval was calculated. MAIN RESULTS: From an initial search of 696 abstracts, 11 trials were obtained in full text for closer examination. Ten trials were excluded and one included. The one included trial, on 30 patients, showed benefit with NPPV when compared to usual medical care alone, with significant improvements in hospitalisation rate, number of patients discharged from emergency department, percent predicted forced expiratory volume in one minute (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR) and respiratory rate. AUTHORS' CONCLUSIONS: The application of NPPV in patients suffering from status asthmaticus, despite some interesting and very promising preliminary results, still remains controversial. Large, prospective randomised controlled trials are therefore needed to determine the role of NPPV in status asthmaticus.

Obstructive sleep apnea presenting as pseudopheochromocytoma: a case report.

Sudden arousal from sleep causes a transient surge in sympathetic nervous activity. Repeated arousals, as occur in obstructive sleep apnea (OSA), are well documented to cause a more prolonged sympathetic overactivity and consequent elevations in 24-h urinary catecholamine levels. We describe here a series of five patients, each presenting with a clinical and biochemical picture indistinguishable from that of pheochromocytoma. Thorough investigations have failed to find catecholamine-secreting tumor in any of these subjects, but all have been diagnosed with OSA. Primary treatment of OSA with nasal continuous positive airways pressure has led to normalization of systemic blood pressure and urinary catecholamines. Pseudopheochromocytoma is therefore a rare, but treatable, presentation of obstructive sleep apnea.

Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.

BACKGROUND: Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.

Mechanisms of exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Some patients are particularly susceptible to develop frequent exacerbations; exacerbation frequency being an important determinant of health related quality of life. Patients with frequent exacerbations (three or more exacerbations per year) have increased induced sputum cytokine interleukin (IL)-6 and IL-8 levels when stable, suggesting that frequent exacerbation is associated with increased airway inflammatory changes. Respiratory viral infections are a major cause of COPD exacerbations, with upper respiratory tract infections (colds) being associated with two-thirds of COPD exacerbations. Rhinovirus has been detected in induced sputum by PCR in 25% of exacerbations, suggesting that rhinovirus may directly infect the lower airway triggering exacerbation. The presence of an upper respiratory tract infection leads to a longer symptom recovery time at exacerbation. At exacerbation induced sputum IL-6 levels were increased compared to stable, though there were no significant increases in IL-8 or sputum cell counts. Sputum IL-6 levels were found to be higher in those patients with symptoms of a common cold. Increased airway eosinophilia has been also found at exacerbation. Other factors including bacterial colonization of the airways, temperature and interactions with environmental pollutants may also play a role in COPD exacerbation.

An evaluation of the reliability and sensitivity of the London Chest Activity of Daily Living Scale (LCADL).

We have previously reported the validity of a new assessment tool; the London Chest Activity of Daily Living Scale (LCADL). This work investigates the reliability and responsiveness of that measure. Reliability was assessed in 19 patients with stable severe chronic obstructive pulmonary disease (COPD); median age (range) 66 (55-79) years, FEV1 mean (SD) 0.91 (0.29) l, by test-retest 4 weeks apart. Responsiveness was assessed in 59 patients; median age (range) 66 (38-84) years, FEV1 mean (SD) 0.87 (0.30) l, who had undergone at least 6 weeks of pulmonary rehabilitation. Test-retest scores of the LCADL showed a strong relationship with one another, Intraclass correlation coefficient Icc=0.93 95%CI (0.82-0.97) demonstrating evidence of good reliability. With the exception of the Domestic component, all domains of the LCADL showed a statistically significant reduction in dyspnoea during ADLs after pulmonary rehabilitation. There was a statistically significant improvement in the total LCADL score (mean difference (95% CI) -5.91 (from -9.23 to -2.60) after rehabilitation. These data support the use of the LCADL as an outcome measure in COPD which is valid, reliable and responsive to change.

Domiciliary oxygen cylinders: indications, prescription and usage.

Oxygen therapy for use in the home can be prescribed in two forms: oxygen concentrators are used to provide long term domiciliary oxygen therapy (LTOT), and oxygen cylinders are used to provide oxygen intermittently for relief of symptoms. In this study prescription and usage of oxygen cylinders in the home were assessed. All patients using oxygen cylinders at home in the London Borough of Tower Hamlets in October 1992 were studied. A questionnaire was sent to each patient; further information was obtained from a questionnaire to the general practitioner and from hospital notes where available. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) were visited at home to measure oxygen saturation levels (SaO2). The main outcome measures were the proportion of oxygen cylinder users who had undergone a full respiratory assessment and the number who might benefit from LTOT. There were 56 patients using oxygen intermittently, 77% with COPD of which 28% had an SaO2 < or = 92%. In these 56 patients 27% had not been assessed by a hospital physician for their chest disease, 58% used their oxygen at least once a day and on average these patients used three cylinders each per month. Most patients using oxygen cylinders at home have a diagnosis of COPD and use oxygen regularly for short term relief of breathlessness; many have not been assessed by a respiratory physician. Measurement of SaO2 suggested that a significant minority might benefit from LTOT and would certainly warrant further evaluation.

Development and validation of a standardized measure of activity of daily living in patients with severe COPD: the London Chest Activity of Daily Living scale (LCADL).

Activities of daily living (ADL) may be severely restricted in patients with COPD and assessment requires evaluation of the impact of disability and handicap on daily life. This study is concerned with the development and validation of a standardized 15-item questionnaire to assess routine ADL. Sixty (33 male, 27 female) patients with severe COPD, mean (SD) FEV1 0.91 (0.43) l, median (range) age 70 (50-82) years, completed a 59-item ADL list previously generated by open-ended interview and by literature review. Patients also performed the Shuttle Walk Test (SWT), and completed the St George's Respiratory Questionnaire (SGRQ), the Nottingham Extended Activity of Daily Living Questionnaire (EADL) and the Hospital Anxiety and Depression score (HAD). Criteria for item reduction in the development of The London Chest ADL scale (LCADL) consisted of removal of items where the majority of respondents showed no limitation in the activity (n = 19), where there was no association with perception of global health (n = 9), where an association with age or gender was detected (n = 4), or where items showed poor reliability on test re-test (n = 9). Fifteen items were identified as core activities of daily living. The LCADL was then compared with other measures of health status in these patients. There were good correlations with the SGRQ activity and impact components (p=0.70; P<0.0001) and (p=0.58; P<0.0001), respectively, and EADL (p=0.45; P<0.001), and a moderate correlation with HAD anxiety (p=0.28; P<0.03). There was a significant relationship between the SWT and LCADL (p=0.58; P<0.0001), suggesting a relationship between impaired exercise performance and lower ADL scores. There was evidence of high internal consistency of the questionnaire with Chronbach's alpha of 0.98. These findings suggest that the LCADL scale is a valid tool for the assessment of ADL in patients with severe COPD.