Predictors of mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive infection that destroys lung tissue in non-immunocompromised patients. Contemporary series suggest 50-85% 5-year mortality, with few prognostic factors identified.A cohort of 387 CPA patients referred to the UK's National Aspergillosis Centre from 1992 to June 2012 was studied until June 2015. The impact of objective and subjective variables including age, sex, previous pulmonary conditions, dyspnoea score, quality of life, serum albumin and C-reactive protein and radiological appearances were assessed using Kaplan-Meier curves, log rank tests and Cox proportional hazards modelling. In samples of patients, retrospective review of time from likely onset of CPA to referral and cause of death were also investigated.Survival was 86%, 62% and 47% at 1, 5 and 10 years, respectively. Increased mortality was associated with nontuberculous mycobacterial infection (hazard ratio 2.07, 95% CI 1.22-3.52; p<0.001) and chronic obstructive pulmonary disease (1.57, 1.05-2.36; p=0.029) as well as higher age (1.053, 1.03-1.07 per year; p<0.001), lower albumin (0.92, 0.87-0.96 per g·L-1), lower activity (1.021, 1.01-1.03 per point increase in St George's Respiratory Questionnaire activity domain; p<0.001) and having one, and especially, bilateral aspergillomas (p<0.001).Several factors impact on mortality of CPA, and can be evaluated as tools to assess CPA prognosis.

The Effect of Fatigue and Fatigue Intensity on Exercise Tolerance in Moderate COPD.

INTRODUCTION: Fatigue is one of the most disabling symptoms in COPD, but little is known about the impact of fatigue on functional disability. We explored the impact of fatigue and fatigue intensity on exercise tolerance after adjusting for other factors using multivariate analysis and compared it to that of dyspnoea. METHODS: A total of 119 patients with mainly moderate-severe stable COPD (38 % women, mean age 66 years) were enrolled. We used the Medical Research Council dyspnoea scores (MRC), Manchester COPD fatigue scale (MCFS) and its three dimensions, Borg scales for fatigue and dyspnoea, six-minute walk distance (6MWD), St George's Respiratory Questionnaire, the BODE index, and the Centre for Epidemiological Study on Depression scale (CES-D), and we measured spirometry, blood gases, systemic inflammatory markers and fat-free mass index (FFMI). RESULTS: Fatigue measured using the MCFS was associated with 6MWD and explained 22 % of the variability in 6MWD (p < 0.001). Fatigue remained associated with 6MWD after adjusting for MRC dyspnoea, FFMI and FEV1, FVC, PaO2, PaCO2, CES-D, TNF-alpha, smoking status, age and gender. We found that 33, 50 and 23 % of patients reported an increase by 2 scores on Borg scales for fatigue, dyspnoea or both at the end of the 6MWT. Fatigue scores (both before and after the 6MWT) were negatively correlated with 6MWD after adjusting for FEV1, FFMI, CES-D score and age (p = 0.007 and 0.001, respectively). CONCLUSION: In moderate stable COPD, fatigue may be a central driver of functional disability, to the same extent as dyspnoea.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

Characterisation of fatigue and its substantial impact on health status in a large cohort of patients with chronic pulmonary aspergillosis (CPA).

INTRODUCTION: Fatigue is a prominent disabling symptom in several pulmonary diseases. Its impact on health status in patients with chronic pulmonary aspergillosis (CPA) has not been investigated. METHODS: A total of 151 CPA patients attending the National Aspergillosis Centre completed Manchester COPD Fatigue Scale (MCFS), St. George's Respiratory Questionnaire (SGRQ) and Medical Research Council (MRC) dyspnoea score. Lung function and BMI were measured. Univariate, multivariate linear and binary analyses, and principal component analysis (PCA) were used. RESULTS: Female patients accounted for 44%. The mean (range) of age was 59.6 (31-83) years, FEV1% was 64 (14-140), BMI was 23.6 (16.3-43.4), SGRQ total score was 56 (4-96.2) and MCFS total score was 30.6 (0-54). PCA showed that 27 items of MCFS loaded on three components; physical, psychosocial and cognitive fatigue, explaining 78.4% of fatigue variance. MCFS score correlated strongly with total SGRQ score (r = 0.83, p < 0.001). Using linear multivariate analysis, fatigue was the strongest factor (beta = 0.7 p < 0.0001) associated with impaired health status, after adjusting for age, BMI, FEV1%, and MRC dyspnoea score. Using patients' 5 self-assessment grades of their health, one-way ANOVA showed that those with "very poor" health status had the highest fatigue scores (45 (±6) (p < 0.001)). Logistic regression analysis showed that fatigue score (OR = 0.9, 95% CI 0.84-0.97; p = 0.005) and FEV1% (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) are significantly associated with self-assessed impaired health status after correcting for age, gender and DLCO%. CONCLUSION: Fatigue is a major component of impaired health status of CPA patients.

Long-term antifungal treatment improves health status in patients with chronic pulmonary aspergillosis: a longitudinal analysis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an infectious disease that progressively destroys lung tissue. To date, no longitudinal data on the efficacy of antifungal treatment on health status in CPA patients exist. METHODS: Using the standardized St George's Respiratory Questionnaire, the health status of 122 patients with was assessed at baseline and quarterly over 12 months. The score range was 0-100, where higher score indicates worse heath status, and a change of ≥4 was deemed the minimal clinically important difference. Lung function, body mass index, Medical Research Council dyspnea scale, disease severity, and demographic data were reported. RESULTS: Mean age of patients was 59 years, and 45% were female. Overall, patients with CPA had substantial health status impairment at baseline. After treatment, 47%-50% gained substantial health improvement with a mean reduction of score of 14 at both 6 and 12 months, whereas 32% deteriorated with a mean rise of score of 11 and 14 after 6 and 12 months of treatment and observation, respectively, and 21% were not much different (stable). Patients gained therapeutic benefit irrespective of their illness severity where >50% of those who had "poor" and "very poor" status at baseline improved with score reduction of ≥4 after 6 months of treatment. Replicating this analysis using a health status category, we found that at least 50% of patients with a "poor/very poor" health status category at baseline improved significantly to "fair" or "good/very good" categories. Side effects burdened health status considerably. In multivariate analysis, dyspnea and disease severity significantly defined health status impairment. CONCLUSIONS: Antifungal therapy improved health status and prevented CPA progression in most patients.

Validity and reliability of the St. George's Respiratory Questionnaire in assessing health status in patients with chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) markedly reduces lung function through progressive lung destruction. To date, however, health status in patients with CPA has not been studied. This is due, in part, to a lack of adequately validated scales. The St. George's Respiratory Questionnaire (SGRQ) is widely used for several chronic respiratory diseases, but not for CPA. We examined the reliability and validity of SGRQ in CPA. METHODS: Eighty-eight patients with CPA completed the SGRQ, the Short Form-36 Health Survey (SF-36), and the Medical Research Council (MRC) dyspnea scale. Lung function and BMI were also measured. Pearson correlation, t test, analysis of variance, and their equivalents for nonparametric data and multivariate linear and binary analyses were used. RESULTS: The SGRQ components (symptoms, activity, and impact) and total scores achieved high internal consistency (Cronbach α = 0.77, 0.91, 0.86, and 0.94), and SGRQ components had good intercorrelation (r ≥ 0.41; P < .001) and correlated well with the total score (r ≥ 0.63; P < .001). There were high, intraclass, correlation coefficients for the total SGRQ and its dimensions (≥ 0.92). The SGRQ scores showed significant correlation with the MRC dyspnea scale and SF-36 components and differentiated between all grades of shortness of breath and different bands of disease severity (P < .05). In addition, patients with greater clinician-rated disease severity had more impairment of health status (P < .006). CPA severity was independently associated with impairment in health status, and COPD comorbidity significantly affected the health status in patients with CPA. CONCLUSIONS: SGRQ demonstrated a significant level of reliability and validity in measuring health status in CPA.

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

INTRODUCTION: Fatigue 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. METHODS: At 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. RESULTS: Four 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 (Cronbach's 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. CONCLUSION: The 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.

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

INTRODUCTION: 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. METHOD: 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. RESULTS: 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). CONCLUSION: This 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 George's 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.