Khaled Al-shair

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

IntroductionCOPD 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.MethodWe 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.ResultsA 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).ConclusionThis study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.

Depression and its relationship with poor exercise capacity, BODE index and muscle wasting in COPD

BACKGROUND The prevalence of depression in stable COPD patients varies markedly, possibly because of use of different scales. We aimed to assess depression using 2 different depression scales and to examine the association between depression and poor exercise performance, BODE index and muscle wasting in clinically stable COPD patients. METHODS 122 stable COPD patients were assessed with the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Brief Assessment Schedule Depression Cards (BASDEC). We also assessed patients with spirometry, bioelectrical impedance analysis, 6-minute walk distance (6MWD), St Georges Respiratory Questionnaire (SGRQ) and MRC dyspnoea and Borg scales. RESULTS The CES-D and BASDEC scales detected almost similar prevalence rates of depression (21% vs 17%) with a Kappa coefficient of 0.68, p<0.0001. The BASDEC scale detected more depression in women and was more closely associated with dyspnoea than the CES-D. COPD severity was associated with depression when using BODE scores but not when GOLD categories were used. Each of the CES-D and BASDEC depression scores were associated with 6MWD after adjusting for FEV1% predicted, gender, age and pack-years (p = <0.0001 and 0.001, respectively). Also, patients with a 6MWD<350 scored significantly higher on both depression scales. Wasted patients appeared to have higher depression scores, but the difference was statistically insignificant. CONCLUSION The administration of different depression scales may affect some of the characteristics of depressed patients rather than the prevalence rate of depression. Depression was associated with poor exercise performance and BODE index in COPD.

Development, dimensions, reliability and validity of the novel Manchester COPD fatigue scale

Introduction: Fatigue is a prominent symptom in chronic obstructive pulmonary disease (COPD) and it has distinctive features; however, there is a need for a robust scale to measure fatigue in COPD. Methods: At baseline, 122 patients with COPD (forced expiratory volume in 1 s (FEV1) 52%, women 38%, mean age 66 years) completed a pilot fatigue scale covering a pool of 57 items and underwent a range of tests, including indicators of mood and a short general fatigue questionnaire. All patients responded to the 57-item scale and it was readministered to a subset of 30 patients. The pilot scale was first subjected to constructive validated shortening steps and then to a principal components analysis. Results: The Manchester COPD fatigue scale (MCFS) consists of 27 items, loading into three dimensions: physical, cognitive and psychosocial fatigue. Internal consistency (Cronbach’s α = 0.97) and test–retest repeatability (r = 0.97, p<0.001) were tested. It had significant convergent validity, correlating with the FACIT (Functional Assessment of Chronic Illness Therapy) fatigue scale and the fatigue in Borg scale at baseline and after a 6 minute walk distance (6MWD) test (r = −0.81, 0.53 and 0.63, respectively, p<0.001). Its scores were associated with BODE, SGRQ (St George’s Respiratory Questionnaire) and MRC (Medical Research Council) dyspnoea scores (r = 0.46, 0.8 and 0.51, respectively, p<0.001). The scale demonstrated meaningful discriminating ability; patients who walked <350 m in a 6MWD test as well as depressed patients (⩾16 scores in the Center for Epidemiologic Study on Depression (CES-D) scale) had nearly twice as high fatigue scores as those who walked ⩾350 m or were not depressed (p<0.001). Conclusion: The MCFS provides a simple, reliable and valid measurement of total and dimensional fatigue in moderate stable COPD.

Examining fatigue in COPD: development, validity and reliability of a modified version of FACIT-F scale

IntroductionFatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.MethodsAt baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.ResultsFour items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining 9 items of the modified FACIT-F and resulted in three interpretable dimensions: i) general (5 items); ii) functional ability (2 items); and iii) psychosocial fatigue (2 items). The modified FACIT-F had high internal consistency (Cronbachs α = 0.91) and it did not fit a uni-dimensional Rasch model, confirming the prior output from the PCA. The correlations between total score and each dimension were ≥ 0.64 and within dimensions ≥0.43 (p < 0.001 for all).The original and modified FACIT-F had significant convergent validity; its scores were associated with SGRQ total score (0.69 and 0.7) and mMRC dyspnoea scores (0.48 and 0.47), (p = <0.001 for all). The scale had meaningful discriminating ability in identifying patients with poor exercise performance and more depressive symptoms.ConclusionThe original and modified FACIT-F are valid and reliable scales in COPD. The modified version is shorter and measures not only total fatigue but also its sub-components in COPD.

P20 Fatigue and Poor Lung Function Are Significantly Associated with Impaired Health-Related Quality of Life (HRQoL) in a Large Cohort of Patients with Chronic Pulmonary Aspergillosis

Introduction Fatigue is a prominent disabling symptom in several chronic pulmonary diseases; however, its impact on HRQoL in patients with chronic pulmonary aspergillosis (CPA) has not been investigated. Method Our 154 patients with CPA completed the Manchester COPD Fatigue Scale (MCFS), Thorax 2009)) and the SGRQ in our specialist referral centre. MCFS measures total fatigue and sub-components comprehensively. Lung function and body mass index were measured. Univariate and multivariate linear and binary analysis, and the principal component analysis (PCA) were used. Results The mean (SD) age (61.1 (10.8)) years and 44% were female; FEV1% (63.3 (24.9)), BMI (23.7 (5.2)), SGRQ total score (55.6 (23.5) and MCFS total score (30 (14.9)). PCA showed that 27 items of MCFS loaded clearly on three components: physical and psychosocial and cognitive fatigue. Univariate analysis showed a strong association between total SGRQ score and MCFS score (r=0.81, p<0.001). Using total SGRQ as a dependent variable, linear multi-variate analysis showed that fatigue was the strongest factor (beta = 0.83 p<0.0001) associated with impaired health status followed by FEV1% (beta= –0.22, p=0.009), but no statistically significant association with age, BMI and pack/years. This model explained 70% of the variance of SGRQ total score. Using patients’ self-assessment grades of SGRQ (Very poor, poor, fair, good and very good), one-way ANOVA showed that patients with “very poor” health status had the highest fatigue scores (45 (6.4)), following by poor (35 (10.1)), fair (30 (10.4)), good (14 (10.9)) and very good (0) (p<0.001). Splitting the group to (very poor and poor) versus (fair, good and very good), the ROC curve analysis indicated significant ability of MCFS and its components to detect change in HS (AUC=0.82; range 0.75–0.9, p<0.0001) as demonstrated in figure 1. Abstract P20 Figure 1 Furthermore, binary regression analysis showed that only fatigue score (OR=0.92, 95% CI 0.87–0.97; p=0.002) and FEV1% (OR=1.04, 95% CI 1.01–1.07, p=0.02) are significantly associated with impaired health status after correcting to age, gender and DLCO%. Conclusion This is the first study directly implicating fatigue as a major factor affecting health-related-quality of life in patients with CPA.

P21 Long Term Antifungal Treatment (LTAFT) is Effectively Associated with Improvement in Health Status (HS) in Patients with Chronic Pulmonary Aspergillosis (CPA)

Introduction CPA is a chronic progressive respiratory infectious disease results in significant lung tissue destruction with a 50%+ 5 year mortality. Response to antifungal therapy is slow, with ∼80% of patients who respond doing so by 6 months. We recently demonstrated the reliability and validity of SGRQ in examining HS in CPA (Chest, in press), and now present longitudinal data on the efficacy of LTAFT in improving HS in CPA patients. Method HS of 98 CPA patients were assessed 3 times over 6 months using the well-established standardised SGRQ. CPA severity was assessed using our published CPA banding system. FEV1, BMI, dyspnoea (using MRC dyspnoea scale) were measured. Results Mean age was 58 years and 48% were female; and 25, 58 and 15 had band 1, 2 and 3 CPA respectively. At visit 2 and 3 (V2 and V3), we found that overall total and domain SGRQ scores were either lower (improved health status) or similar compared to V1 (table 1). Abstract P21 Table 1 Categorizing the cohort by those who reported improvement or deterioration by a total SGRQ score of ≥4 at V3 comparing to V1, we found that 43% improved, 22% remained stable and 35% deteriorated. The median (IQR) of total SGRQ score of the improved group at V3 was 58 (42–66) compared to 71 (60–79) at V1; and for the deteriorated group was 67.5 (57–76) at V3 compared to 62 (41–67)) at V1. The deteriorated were older (62 (9.8) years versus 56.1 (9.3) (p=0.008); and tended to have lower BMI, more dyspnoea and worse lung function. Moreover, binary regression multivariate analysis showed that age maintained its association with deterioration in HS (OR 1.13, 95% CI 1.01–1.26, p=0.03) after correcting for gender, BMI and FEV1%. Of the 37 patients started on an antifungal agent at V1 who took it for 3+ months (including a 3 week IV course of amphotericin B), 22 (59%) improved, 11 (30%) were stable and 4 (11%) deteriorated at V3. Conclusion LTAFT prevented/reduced the progression of CPA and patients preserved overall good HS. More therapeutic approaches for this progressive disease are urgently needed.