Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD

<p>Abstract</p> <p>Introduction</p> <p>COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales.</p> <p>Method</p> <p>We assessed 120 patients with moderate COPD (FEV₁% 52, men 62%, age 66). Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS) and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6.</p> <p>Results</p> <p>A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007). TNF-α remained positively correlated with depression (p = 0.024) after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV₁%, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044). Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7) had higher mean CES-D depression score than the rest of the sample (p = 0.03). Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054).</p> <p>Conclusion</p> <p>This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.</p

Assimilation of word-final nasals to following word-initial place of articulation in United Kingdom English.

Using very large speech corpora, we can study rare but systematic pronunciation patterns in spontaneous speech. Previous studies have established that word-final alveolar consonants in English (/t/, /d/, /n/, /s/ and /z/) vary their place of articulation to match a following word-initial consonant, e.g., "ran quickly" → "ra[] quickly." Assimilation of bilabial or velar nasals, e.g., "alar[] clock" for "alarm clock," is unexpected according to linguistic frameworks such as underspecification theory. The existence of systematic counterexamples would challenge that theory, but these might have been previously overlooked because they are infrequent. From the c. 8-million word Audio BNC (http://www.phon.ox.ac.uk/AudioBNC) we extracted more than 4,000 tokens of relevant word pairs, to determine whether non-alveolar assimilations occur and with what distribution. Word and segment boundaries were obtained by forced alignment, and F1-F3 formant frequencies were estimated using Praat. Formant frequencies in assimilation environments were compared to non-assimilating controls (e.g., them down vs. them back/then down). We also examined patterns of variability in different contexts. We will present evidence that velar and bilabial nasals sometimes do assimilate, though less frequently than alveolars

Temporal clustering of exacerbations in chronic obstructive pulmonary disease.

RATIONALE: Exacerbations 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. OBJECTIVES: To assess whether exacerbations are random events, or cluster in time. METHODS: A 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. MEASUREMENTS AND MAIN RESULTS: The 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). CONCLUSIONS: Exacerbations 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

Evaluation of psychological and physiological predictors of fatigue in patients with COPD

BACKGROUND: Fatigue in COPD impairs functional status; however there are few studies examining mechanistic pathways of this symptom. The aims of this study are to compare fatigue between COPD patients and healthy age-matched subjects, and to identify predictors of fatigue in COPD. METHODS: Seventy four COPD patients, mean age 69.9 (49-87) yrs, mean (SD) % predicted FEV1 46.5 (20.0) % and FEV1/FVC ratio 0.45 (0.13) and 35 healthy subjects, mean age 67.1 (50-84) yrs completed the Multidimensional Fatigue Inventory (MFI 20). Patients' assessment included Depression (HADS), lung function, BMI, muscle strength, incremental shuttle walk test (ISWT), exercise oxygen saturation (SpO2), Borg breathlessness (CR-10) and exertion (RPE). Serum level of Interleukin 6 (IL-6) was recorded. Differences in MFI 20 between groups were examined and predictors of fatigue identified using logistic regression. RESULTS: Significant differences (p < 0.01) were found between the COPD and healthy subjects for all MFI 20 dimensions. There were significant differences when classified according to GOLD and dyspnoea stages for selected dimensions only. Predictors of General Fatigue were depression, muscle strength and end SpO2 (R2 = .62); of Physical Fatigue: depression, % predicted FEV1, ISWT and age (R2 = .57); Reduced Activity: % predicted FEV1, BMI and depression (R2 = .36); Reduced Motivation: RPE, depression and end SpO2 (R2 = .37) and Mental Fatigue: depression and end SpO2 (R2 = .38). CONCLUSION: All dimensions of fatigue were higher in COPD than healthy aged subjects. Predictive factors differ according to the dimension of fatigue under investigation. COPD-RF is a multi component symptom requiring further consideration

Increasing physical activity in people with COPD

Levels of physical activity tend to be reduced in people with COPD. Matthew Armstrong discusses the benefits of improving activity levels in this group of patients It is well acknowledged that levels of physical activity in patients with chronic obstructive pulmonary disease (COPD) are considerably lower than healthy-age matched individuals, with physical inactivity recognised as a key predictor of hospitalisation and mortality. Pulmonary rehabilitation (PR) has become a major tool for managing symptoms of COPD and the associated extra-pulmonary effects. However, inconsistencies surrounding its effectiveness in terms of improving physical activity remain due to the complex nature of physical activity. To overcome these inconsistencies, both pharmacological and behavioural interventions have been documented to aid improvements in physical activity, with behavioural interventions alongside PR found to be the most effective tool to promote levels of physical activity. Health professionals must therefore look to incorporate an interdisciplinary approach in order to best achieve improvements in physical activity levels in patients with COPD