R Baghai-Ravary

Temporal Clustering of Exacerbations in Chronic Obstructive Pulmonary Disease

RATIONALEnExacerbations are important events in chronic obstructive pulmonary disease. Preventing exacerbations is a key treatment goal. Observational data suggest that after a first exacerbation, patients may be at increased risk of a second exacerbation, but this has not been specifically studied. We hypothesized that exacerbations may cluster together in time, a finding that would have important implications for targeting preventative interventions and the analysis of clinical trial data.nnnOBJECTIVESnTo assess whether exacerbations are random events, or cluster in time.nnnMETHODSnA total of 297 patients in the London chronic obstructive pulmonary disease cohort recorded daily symptoms and were assessed for a total of 904 patient-years. The observed timing of second exacerbations after an initial exacerbation was compared with that expected should exacerbations occur randomly.nnnMEASUREMENTS AND MAIN RESULTSnThe observed timing distribution of second exacerbations differed significantly (P < 0.001) from the expected exponential function (shape parameter of the fitted Weibull function, 0.966 [95% confidence interval, 0.948-0.985]), suggesting that more second exacerbations occurred sooner than later and that exacerbations cluster together in time. Twenty-seven percent of first exacerbations were followed by a second recurrent event within 8 weeks. Approximately one third of exacerbations were recurrent exacerbations. Although initial exacerbations were milder than isolated events, they were not less likely to receive treatment, and under-treatment of initial events is not a plausible explanation for exacerbation recurrence. Recurrent exacerbations contribute significantly to overall exacerbation frequency (rho = 0.81; P < 0.0001).nnnCONCLUSIONSnExacerbations are not random events but cluster together in time such that there is a high-risk period for recurrent exacerbation in the 8-week period after an initial excerbation.

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 Georges 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.

Serum IP-10 as a Biomarker of Human Rhinovirus Infection at Exacerbation of COPD

BACKGROUNDnHuman rhinovirus (HRV) is the most frequent virus associated with COPD exacerbations. Viral infections increase exacerbation severity and likelihood of hospitalization. As ease of sampling blood makes serum a more practical marker than sputum, we investigated whether changes in serum interferon-gamma-inducible protein 10 (IP-10) from baseline to exacerbation were higher in airway HRV-positive exacerbations and whether IP-10 levels related to HRV load.nnnMETHODSnOne hundred thirty-six patients with COPD and 70 controls were included over 2 years and 72 exacerbations sampled. HRV positivity and load were determined by reverse transcriptase-polymerase chain reaction in nasopharyngeal swabs and/or sputum at baseline and exacerbation. IP-10 was measured by enzyme-linked immunosorbent assay in serum and compared with HRV load.nnnRESULTSnAt baseline, serum IP-10 was higher in patients with COPD than controls; medians were 149.4 pg/mL (103-215) and 111.7 pg/mL (82-178), P = .02. The presence of HRV at baseline did not increase IP-10: patients with COPD, 166.9 pg/mL (110-240) and 149.4 pg/mL (103-215), P = .30; controls, 136.4 pg/mL (77-204) and 111.7 pg/mL (82-178), P = .53. IP-10 increased significantly from baseline to exacerbation in HRV-positive exacerbations: 154.9 pg/mL (114.0-195.1) to 207.5 pg/mL (142.1-333.5), P = .009. There was no change in IP-10 between baseline and exacerbation in HRV-negative exacerbations: 168.3 pg/mL (94.3-249.8) and 175.6 pg/mL (107.2-290.4), P = .49. At exacerbation, IP-10 correlated with sputum viral load: rho = 0.48; P = .02. In receiver operating characteristics analysis, the combination of IP-10 and coryzal symptoms gave an area under the curve of 0.82 (95% CI, 0.74-0.90).nnnCONCLUSIONSnIP-10 increases from baseline to exacerbation in HRV-positive exacerbations and correlates with sputum HRV load. Serum IP-10 may be useful as a novel marker for these events.

Determinants and impact of fatigue in patients with chronic obstructive pulmonary disease.

RATIONALEnThe perception of fatigue in COPD has been associated with reduced health status. We have shown that exacerbations are associated with reduced activity and health status. However, the relationship between fatigue and exacerbation is unknown.nnnOBJECTIVESnTo investigate the hypothesis that increased fatigue is related to physical inactivity and COPD exacerbations.nnnMETHODSnFatigue was studied in COPD and age-matched control subjects. The relationship between fatigue and stable patient characteristics in COPD, and the effect of exacerbation on fatigue were evaluated.nnnMEASUREMENTSn107 COPD patients mean age 69 years (range 43-86), FEV(1) 53% (SD 21), and 30 aged-matched control subjects; Functional Assessment of Chronic Illness Therapy-Fatigue Scale, Centre for Epidemiological Studies Depression Scale.nnnMAIN RESULTSnFatigue in COPD patients was significantly increased compared to control subjects (mean 35.3 units (SD 11.0) versus 43.2 (10.5), p=0.001). Increase in fatigue in COPD was related to reduced time spent outdoors (r=-0.43, p<0.001), increase in depression (r=-0.59, p<0.001) and annual exacerbation frequency (r=-0.27, p=0.005). Fatigue increased at exacerbation in 31/32 patients. Overall, fatigue increased by 8.3 units (5.9), p<0.001. Change in fatigue at exacerbation was related to increase in depression (r=-0.46, p=0.008). Fatigue recovered at 6 weeks following exacerbation.nnnCONCLUSIONSnThe perception of fatigue increased in patients with COPD compared to age-matched control subjects, and associated with morbidity when patients were stable and at exacerbation.

The birth and re-birth of respiratory medicine—notes from the British Thoracic Society Winter Meeting 2006

The annual Winter British Thoracic Society (BTS) meeting in December 2006 provided us with yet another exciting forum for both scientists and clinicians to share advances in respiratory medicine. The meeting consisted of inspiring, novel and interesting work, presented by students and non-clinicians, as well as world renowned respiratory physicians. Professor Stephen Holgate, in his address as President of the BTS entitled “The birth and re-birth of respiratory medicine”, spoke of changes and shared his visions for the future. Dr Alex Richter and Dr Clare Sander deserve congratulations for their success in the Young Investigator Prizes. In this review we highlight some of the important spoken and abstract sessions from the meeting.nnChronic obstructive pulmonary disease (COPD) was well represented at the meeting this year, with a stimulating symposium focusing on the science and impact of exacerbations. Spoken sessions on a novel in vivo model of human rhinovirus infection1 and application of real-time quantitative polymerase chain reaction for the detection of bacteria2 opened platforms for improved understanding of the infectious mechanisms of exacerbations. There was evidence to suggest that prolonged exacerbation in smokers may be related to impaired neutrophil activation.3 Smoking cannabis was related to greater airflow obstruction than cigarettes,4 re-enforcing the need to address all smoking cessation.nnThe consequences of depression in COPD, in particular the associations with mental and general fatigue,5 relation to reduced time spent outdoors, health-related quality of life6 and failure to complete pulmonary rehabilitation,7 were discussed in several sessions. Randomised controlled trials are needed to investigate reports of benefit from pulmonary rehabilitation initiated during admission for acute exacerbation8 and in maintenance of weekly supervised exercise sessions.9 An assessment of the national availability, need, cost-effectiveness and outcome of pulmonary rehabilitation10,11 may be facilitated by a …