Frailty and Exacerbation of Chronic Obstructive Pulmonary Disease: Is There Any Association?

Purpose: This study investigated if individuals with chronic obstructive pulmonary disease (COPD) and frailty are more likely to have acute exacerbations of COPD or require hospitalization for exacerbation than those without frailty. Patients and Methods: Data on 135 outpatients with stable COPD were analyzed with the Cox proportional hazards model to assess the risk of future events. The Kihon Checklist was administered at baseline to classify the participants as robust, pre-frail, or frail. The follow-up period was a maximum of six and a half years. Results: In all, 76 patients (56.3%) experienced an exacerbation and 46 (34.1%) were hospitalized due to it. Multivariate Cox proportional hazards analysis that accounted for FEV1 and sex showed that the frail group was more likely to face future risks of COPD exacerbations [Hazard ratio 1.762 (95% CI 1.011-3.070), p=0.046] and hospitalizations for exacerbation [2.238 (1.073-4.667), p=0.032] than the robust group. No significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail either in exacerbations or hospitalizations. When comparing the C-indices for frailty and FEV1, the former index (exacerbation 0.591 and hospitalization 0.663) did not exceed the latter (0.663 and 0.769) in either analysis. Conclusion: Frail COPD patients have a more unfavorable future risk of acute exacerbations of COPD and hospitalizations for exacerbation than robust patients. However, no significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail, suggesting that the future risk for COPD patients with frailty is only higher compared to those who are considered robust. Additionally, FEV1 was found to be a more reliable predictor of future events than measures of frailty.

Comparison of Predictive Properties between Tools of Patient-Reported Outcomes: Risk Prediction for Three Future Events in Subjects with COPD.

BACKGROUND: Patient-reported outcome (PRO) measures must be evaluated for their discriminatory, evaluative, and predictive properties. However, the predictive capability remains unclear. We aimed to examine the predictive properties of several PRO measures of all-cause mortality, acute exacerbation of chronic obstructive pulmonary disease (COPD), and associated hospitalization. METHODS: A total of 122 outpatients with stable COPD were prospectively recruited and completed six self-administered paper questionnaires: the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Baseline Dyspnea Index (BDI), Dyspnoea-12, Evaluating Respiratory Symptoms in COPD and Hyland Scale at baseline. Cox proportional hazards analyses were conducted to examine the relationships with future outcomes. RESULTS: A total of 66 patients experienced exacerbation, 41 were hospitalized, and 18 died. BDI, SGRQ Total and Activity, and CAT and Hyland Scale scores were significantly related to mortality (hazard ratio = 0.777, 1.027, 1.027, 1.077, and 0.951, respectively). The Hyland Scale score had the best predictive ability for PRO measures, but the C index did not reach the level of the most commonly used FEV1. Almost all clinical, physiological, and PRO measurements obtained at baseline were significant predictors of the first exacerbation and the first hospitalization due to it, with a few exceptions. CONCLUSIONS: Measurement of health status and the global scale of quality of life as well as some tools to assess breathlessness, were significant predictors of all-cause mortality, but their predictive capacity did not reach that of FEV1. In contrast, almost all baseline measurements were unexpectedly related to exacerbation and associated hospitalization.

Are Fatigue and Pain Overlooked in Subjects with Stable Chronic Obstructive Pulmonary Disease?

Although there have been many published reports on fatigue and pain in patients with chronic obstructive pulmonary disease (COPD), it is considered that these symptoms are seldom, if ever, asked about during consultations in Japanese clinical practice. To bridge this gap between the literature and daily clinical experience, the authors attempted to gain a better understanding of fatigue and pain in Japanese subjects with COPD. The Brief Fatigue Inventory (BFI) to analyse and quantify the degree of fatigue, the revised Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2) for measuring pain and the Kihon Checklist to judge whether a participant is frail and elderly were administered to 89 subjects with stable COPD. The median BFI and SF-MPQ-2 Total scores were 1.00 [IQR: 0.11-2.78] and 0.00 [IQR: 0.00-0.27], respectively. They were all skewed toward the milder end of the respective scales. A floor effect was noted in around a quarter on the BFI and over half on the SF-MPQ-2. The BFI scores were significantly different between groups regarding frailty determined by the Kihon Checklist but not between groups classified by the severity of airflow limitation. Compared to the literature, neither fatigue nor pain are considered to be frequent, important problems in a real-world Japanese clinical setting, especially among subjects with mild to moderate COPD. In addition, our results might suggest that fatigue is more closely related to frailty than COPD.

Comparison between tools for measuring breathlessness: Cross-sectional validation of the Japanese version of the Dyspnoea-12.

INTRODUCTION: The Dyspnoea-12 (D-12) is a brief, easy to complete questionnaire for measuring breathlessness. OBJECTIVES: To facilitate further efforts to measure dyspnoea in real clinical settings, the authors aimed to develop and validate a Japanese version of the D-12 and also compare the D-12 with the Baseline Dyspnea Index (BDI) and the Activity component of the St. George's Respiratory Questionnaire (SGRQ). METHODS: The standardized procedure in accordance with international guidelines was used to create the translation. A validation study with a cross-sectional observational design was conducted on 122 subjects with stable chronic obstructive pulmonary disease (COPD). RESULTS: The internal consistency of the D-12 was high (Cronbach's coefficient α = 0.883) and similar to that of the BDI (α = 0.824) and SGRQ Activity (α = 0.872). The relationships between tools were statistically significant (|Rs | = 0.53 to 0.66). Although the scores obtained from all three tools were skewed toward the milder end of the respective scales, this deviation was most prominent in the D-12 with a floor effect of 48.4%. CONCLUSION: The Japanese version of the D-12 was successfully validated, but we should be careful of any floor effect and marked skew to the mild end of the scale, especially in subjects with mild COPD.

Is Blood Eosinophil Count a Biomarker for Chronic Obstructive Pulmonary Disease in a Real-World Clinical Setting? Predictive Property and Longitudinal Stability in Japanese Patients.

The authors examined predictive properties and the longitudinal stability of blood eosinophil count (BEC) or three strata (<100 cells/mm3, 100-299 cells/mm3 and ≥300 cells/mm3) in patients with chronic obstructive pulmonary disease (COPD) for up to six and a half years as part of a hospital-based cohort study. Of the 135 patients enrolled, 21 (15.6%) were confirmed to have died during the follow-up period. Episodes of acute exacerbation of COPD (AECOPD) were identified in 74 out of 130 available patients (56.9%), and admission due to AECOPD in 35 out of 132 (26.5%). Univariate Cox proportional hazards analyses revealed that almost all the age, forced expiratory volume in 1 s (FEV1) and health status measures using St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) Score were significantly related to these types of events, but the relationship between age and AECOPD did not reach statistical significance (p = 0.05). Neither BEC nor the three different groups stratified by BEC were significant predictors of any subsequent events. There were no significant differences in the BEC between Visits 1-3 (p = 0.127, Friedman test). The ICC value was 0.755 using log-transformed data, indicating excellent repeatability. In the case of assigning to strata, Fleiss' kappa was calculated to be 0.464, indicating moderate agreement. The predictive properties of BEC may be limited in a real-world Japanese clinical setting. Attention must be paid to the fact that the longitudinal stability of the three strata is regarded as moderate.

Are frailty and patient-reported outcomes independent in subjects with asthma? A cross-sectional observational study.

INTRODUCTION: This study examined the possible associations between frailty and patient-reported outcomes (PROs) in elderly patients with asthma. METHODS: Participants completed the Kihon Checklist for frailty screening as well as the following tools for measuring generic- and disease-specific health-related quality of life (HRQOL) and asthma control; the Medical Outcomes Study 36-item short form (SF-36), the Hyland Scale (global scale), the Asthma Quality of Life Questionnaire (AQLQ), the Asthma Control Test (ACT), and the Asthma Control Questionnaire (ACQ). RESULTS: Of 69 consecutive outpatients with asthma, 38 (55.1%), 21 (30.4%), and 10 (14.5%) were classified as robust, pre-frail, and frail, respectively. Eight out of 52 patients with asthma in the elderly (AIE) (>65 years old) (15.4%) were considered as being frail. The Kihon Checklist total score was significantly correlated with all the scores obtained from the SF-36, Hyland Scale, AQLQ, ACT, and ACQ. All these scores were significantly different between groups with and without frailty. From the viewpoint of correlation coefficient, SF-36 Physical Functioning correlated most strongly with a coefficient of -0.68 (P < .01), and the Hyland Scale score was second (RS = -0.46, P < .01). The correlations between the Kihon Checklist total score and lung function parameters were weak or negative (|RS | < 0.35). DISCUSSION: There were significant associations between frailty and PROs, particularly generic perception of HRQOL. Since the Kihon Checklist and PROs such as the HRQOL overlap somewhat in their evaluation of the patients' condition, there might be some similarities in the conceptual frameworks of frailty and quality of life.

Comparison between electronic and paper versions of patient-reported outcome measures in subjects with chronic obstructive pulmonary disease: an observational study with a cross-over administration.

OBJECTIVES: A wide range of electronic devices can be used for data collection of patient-reported outcome (PRO) measures in subjects with chronic obstructive pulmonary disease (COPD). Although comparisons between electronic and paper-based PRO measures have been undertaken in asthmatics, it is currently uncertain whether electronic questionnaires work equally as well as paper versions in elderly subjects with COPD. The aim of this study was to compare the responses to paper and electronic versions of the Evaluating Respiratory Symptoms in COPD (E-RS) and the COPD Assessment Test (CAT). DESIGN: A randomised cross-over design was used to compare the responses to paper and electronic versions of the two tools. The interval between the two administrations was 1 week. SETTING: Electronic versions were self-administered under supervision using a tablet computer at our outpatient clinic (secondary care hospital in Japan) while paper questionnaires completed at home were requested to be returned by mail. It was intended that half of the patients completed the electronic versions of both questionnaires first, followed by the paper versions while the other half completed the paper versions first. PARTICIPANTS: Eighty-one subjects with stable COPD were included. RESULTS: The E-RS total scores (possible range 0-40) were 6.8±7.4 and 5.0±6.6 in the paper-based and electronic versions, respectively, and the CAT scores (possible range 0-40) were 10.0±7.4 and 8.6±7.8. In both questionnaires, higher scores indicate worse status. The relationship between electronic and paper versions showed significant reliability for both the E-RS total score and CAT score (intraclass correlation coefficient=0.82 and 0.89, respectively; both p<0.001). However, both the E-RS total and CAT scores were significantly higher in the paper versions (p<0.05). CONCLUSIONS: In both cases, the two versions of the same questionnaire cannot be used interchangeably even though they have both been validated.

Comparison of patient-reported outcomes during acute exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: The aim of this study was to investigate which patient-reported outcome measure was the best during the recovery phase from severe exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: The Exacerbations of Chronic Pulmonary Disease Tool (EXACT), the COPD Assessment Test (CAT), the St George's Respiratory Questionnaire (SGRQ), the Dyspnoea-12 (D-12) and the Hyland Scale (global scale) were recorded every week for the first month and at 2 and 3 months in 33 hospitalised subjects with acute exacerbation of COPD (AECOPD). RESULTS: On the day of admission (day 1), the internal consistency of the EXACT total score was high (Cronbach's alpha coefficient=0.89). The EXACT total, CAT, SGRQ total and Hyland Scale scores obtained on day 1 appeared to be normally distributed. Neither floor nor ceiling effects were observed for the EXACT total and SGRQ total scores. The EXACT total score improved from 50.5±12.4 to 32.5±14.3, and the CAT score also improved from 24.4±8.5 to 13.5±8.4 during the first 2 weeks, and the effect sizes (ES) of the EXACT total and CAT score were -1.40 and -1.36, respectively. The SGRQ, Hyland Scale and D-12 were less responsive, with ES of -0.59, 0.96 and -0.90, respectively. DISCUSSION: The EXACT total and CAT scores are shown to be more responsive measures during the recovery phase from severe exacerbation. Considering the conceptual framework, it is recommended that the EXACT total score may be the best measure during the recovery phase from AECOPD. The reasons for the outstanding responsiveness of the CAT are still unknown.

[A case of myeloid sarcoma in the anterior mediastinum].

We report a case of myeloid sarcoma in the anterior mediastinum. The patient was a 33-year-old man with a chief complaint of right shoulder pain, right upper limb edema, and cough. Chest contrast-enhanced computed tomography (CT) revealed a partially enhanced anterior mediastinal tumor. A CT-guided biopsy was then performed, and a Hematoxylin-eosin (HE) stain revealed mitosis of tumor cells and other cells, including eosinophils. Immunohistochemical stains with myeloperoxidase, CD34, CD43, CD68 and c-Kit tests were positive for tumor cells. Due to a pathological diagnosis of myeloid sarcoma, he was treated with chemotherapy based on a diagnosis of acute myelogenous leukemia. After complete remission was obtained, the patient visited another hospital to receive an unrelated bone marrow transplantation. Although it rarely occurs as a mediastinal tumor, the prognosis of myeloid sarcoma is unfavorable, and thus should be taken into consideration as a differential diagnosis.

[A case of severe asthma responsive to omalizumab treatment despite a low serum IgE level and lack of sensitized allergens].

A 49-year-old female patient suffering from severe intractable asthma uncontrolled even with high-dose inhaled glucocorticosteroids (fluticasone 1000 µg/day+ciclesonide 800 µg/day), salmeterol inhaler (100 µg/day) and oral betamethasone (1 mg/day) was admitted to our hospital because of severe asthma attack. The total serum IgE level was low at 9 (IU/mL). Though perennial allergens was also negative, administration of 150 mg omalizumab was started in August 2009 with the patient's consent, resulting in noticeable improvements in asthma symptoms and the peak expiratory flow (PEF) were achieved. Due to her weight gain and general malaise, the drug was discontinued after the second administration, resulting in worsening of asthma symptoms. Omalizumab therapy was restarted in January 2010 and marked improvements in asthma symptoms and PEF were noted. The effects continued for approximately three weeks after administration. After the sixth administration, the dose of oral betamethasone successfully reduced to 0.5 mg/day. When comparing the six-month pre- and post-omalizumab therapy period, asthma-related events such as unscheduled hospital visits were also reduced, and the dose of oral betamethasone could also be reduced to 64% of the pre-therapy period after the omalizumab treatment. This case strongly suggests the therapeutic effect of omalizumab in the treatment of severe intractable asthma with low serum IgE level without identifiable allergens.

[A case of rapidly progressing lung spindle cell carcinoma presenting as Pancoast syndrome].

We report a case of rapidly progressing spindle cell carcinoma presenting as Pancoast syndrome. The patient was a 59-year-old woman with a chief complaint of right forearm paresthesia. A chest computed tomography revealed a huge tumor in S1 and S2 in the right lung, invading the upper mediastinum and the first rib. A CT-guided lung biopsy was performed. H-E stain of the tissue revealed spindle-shaped tumor cells proliferating diffusely in a streaming pattern without definitive squamous or glandular differentiation. Immunohistochemical stains with CAM 5.2 and vimentin were positive for tumor cells. Based on a pathological diagnosis of spindle cell carcinoma (cT4N3M1, stage IV) she was treated with chemoradiotherapy. Despite treatment, the patient died 6 months after presenting.

Maximizing venous outflow after right hepatic living donor liver transplantation with a venous graft patch.

Between March 2002 and September 2004, 36 patients at Mie University Hospital underwent living donor liver transplantation (LDLT) of a right lobe graft without the middle hepatic vein. The patients were divided into two groups: group I (n = 25) received ordinary hepatic vein anastomoses, and group II (n = 11) received a venous graft patch in the subsequent procedure. Between groups, we compared hepatic vein blood flow (ultrasound), liver volume (CT scan), laboratory data, and ascitic fluid volume. Outflow block developed as a complication in 1 patient in group I. Hepatic vein blood flow on postoperative day (POD) 3 was significantly better in group II, and hepatic vein waveforms of most group II patients showed the triphasic pattern, especially on PODs 3 and 5. The total bilirubin and aspartate aminotransferase values on POD 1 were significantly better in group II, and daily ascitic fluid volume on PODs 3 and 5 was significantly lower in group II. Thus, modified venoplasty with a graft patch in the right hepatic LDLT not only improved hepatic vein hemodynamics (based on the ultrasound findings), but also improved liver function and decreased daily ascitic fluid volume.