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

Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV₁) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment.</p> <p>Methods</p> <p>We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities.</p> <p>Results</p> <p>R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores.</p> <p>Conclusions</p> <p>IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.</p

Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype.

Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552)

Clinical characteristics of COPD patients with tidal expiratory flow limitation

James Dean,1 Umme Kolsum,1,2 Paul Hitchen,1 Vandana Gupta,1 Dave Singh1,2 1Medicines Evaluation Unit, Manchester, 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK Abstract: We have used impulse oscillometry to identify COPD patients with tidal expiratory flow limitation (EFL), which is a measurement related to small airway disease. We report that 37.4% of COPD patients had EFL; these patients had multiple clinical characteristics of more severe disease including lower forced expiratory volume in 1 second values, greater hyperinflation, reduced exercise performance, and increased small airway impairment. We highlight that EFL can be used to identify a subgroup of COPD patients with distinct characteristics associated with small airway disease. Keywords: COPD, expiratory flow limitation, IOS, small airway, reactanc

The Manchester Respiratory-related Sleep Symptoms scale for patients with COPD: development and validation

Naimat Khan,1 J&oslash;rgen Vestbo,2 Adam Garrow,3 Pradeep Karur,4 Umme Kolsum,5 Sarah Tyson,6 Dave Singh,7 Janelle Yorke8 1The Medicines Evaluation Unit, Wythenshawe Hospital, Manchester, UK; 2University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 3Division of Population Health, University of Manchester, Manchester, UK; 4Medicines Evaluation Unit, Manchester, UK; 5University of Manchester, Manchester, UK; 6University of Manchester, School of Health Sciences, Manchester Academic Health Sciences Centre, Manchester, UK; 7University of Manchester, The Medicines Evaluation Unit, Manchester, UK; 8University of Manchester, School of Health Sciences, Manchester, UK Background: In COPD disturbed sleep is related to exacerbation frequency, poor quality of life, and early mortality. We developed the Manchester Respiratory-related Sleep Symptoms scale (MaRSS) to assess sleep-time symptoms in COPD. Methods: Focus groups including COPD and age-matched controls were used to develop an item-list, which was then administered to COPD patients and age-matched controls in a cross-sectional study. Hierarchical and Rasch analysis informed item selection and scale unidimensionality. Construct validity was examined using Pearson&rsquo;s correlation with the Sleep Problems Index, St George&rsquo;s Respiratory Questionnaire (SGRQ), and FACIT-Fatigue scale. MaRSS change scores from baseline (stable) to exacerbation were assessed in a separate substudy of COPD patients. Results: Thirty-six COPD patients and nine age-matched controls produced an initial 26-item list. The cross-sectional study involved 203 COPD patients (male: 63%, mean age 64.7 years) and 50 age-matched controls (male: 56%, mean age 65.8 years). Eighteen items were removed to develop an eight-item unidimensional scale covering breathlessness, chest tightness, cough, sputum production, lack of sleep, and medication use. MaRSS scores significantly correlated with sleep problems, SGRQ Total, and FACIT-Fatigue (r=0.58&ndash;0.62) and demonstrated a good fit to the Rasch model (chi-squared=29.2; P=0.04). In the substudy, MaRSS scores demonstrated a moderate effect size from baseline to exacerbation visit in 27 patients with 32 exacerbation episodes (Cohen&rsquo;s d=0.6). Conclusion: The MaRSS is a reliable, valid, and clinically responsive measure of respiratory-related symptoms that disturb sleep. It is simple to use and score, making it suitable for research and clinical practice. Keywords: COPD, sleep, dyspnea, cough, sputum, outcome measur