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 Disease Severity Classifications of Chronic Obstructive Pulmonary Disease: GOLD vs. STAR in Clinical Practice.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR), with four grades of severity in subjects with an FEV1/FVC ratio <0.70: STAR 1 ≥0.60 to <0.70, STAR 2 ≥0.50 to <0.60, STAR 3 ≥0.40 to <0.50, and STAR 4 <0.40. PURPOSE: The aim of this study was to compare the staging of COPD using the GOLD and STAR classifications in clinical practice. METHODS: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. RESULTS: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3 + 4 groups, with the GOLD 1 group used as the reference [hazard ratio 4.222 (95% CI 1.298-13.733), p = 0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3 + 4. St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3 + 4, but not between STAR 1 and STAR 2. CONCLUSION: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Is Frailty a Mortality Predictor in Subjects with Chronic Obstructive Pulmonary Disease?

Background: Chronic obstructive pulmonary disease (COPD) has been frequently associated with frailty. The association between frailty and mortality in patients with COPD has not yet been fully elucidated and it remains controversial whether frailty or airflow limitation is more important in predicting mortality. Methods: A total of 141 subjects with stable COPD completed pulmonary function tests and the Kihon Checklist at baseline between 2015 and 2022 and were followed for a maximum of 95 months. Using the Kihon Checklist Total score, we classified patients' frailty status as robust (0-3), pre-frail (4-7), and frail (8-25). Results: At baseline, there were 67 (47.5%) in the robust group, 36 (25.5%) pre-frail, and 38 (27.0%) frail. Death was confirmed in 29 (20.5%). Univariate Cox proportional hazards analyses revealed that all predictive relationships of frailty and airflow limitation with mortality were statistically significant, and the C-index was similar, ranging from 0.63 to 0.66. According to the Log rank test and the Cox regression model, there was a significant difference between the frail and robust groups, (p=0.004 and p=0.005, respectively). No significant differences were found in either comparison with the pre-frail group. When stratification of frailty and FEV1 as well as sex were included as explanatory variables, multivariate Cox regression analysis showed a significant difference between the robust and frail groups with respect to mortality when the robust group was used as the reference (p=0.024). The robust and pre-frail groups did not differ significantly (p=0.163). Conclusion: The mortality of frail COPD patients is higher than those classed as robust. Despite frailty being a substantial mortality predictor, it is uncertain whether or not it is a better predictor than FEV1.

The Conceptual Independence of Health Status, Respiratory Symptoms and Dyspnea in Chronic Obstructive Pulmonary Disease in Real Clinical Practice.

The hypothesis that health status is the highest ranking concept, followed by respiratory symptoms and dyspnea as the lowest ranking concepts in subjects with chronic obstructive pulmonary disease (COPD) was tested in a real clinical setting with 157 subjects with stable COPD. Spearman's rank correlation coefficients for scores of health status using the COPD Assessment Test (CAT), respiratory symptoms using the COPD Evaluating Respiratory Symptoms (E-RS) and dyspnea using Dyspnea-12 (D-12) between any two were 0.6 to 0.7. Upon categorizing the patients as "abnormal" or "normal" according to the threshold, it was found that 30 patients (19.1%) had dyspnea, respiratory symptoms and impaired health status. Dyspnea was considered an important part of respiratory symptoms, though seven patients had dyspnea but no respiratory symptoms. There were 10 patients who had respiratory symptoms without dyspnea but without health status problems. Furthermore, there were six patients who had both dyspnea and respiratory symptoms but whose health status was classified as fine. Thus, the hypothesis was correct in approximately 85% of cases.

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.

How different are COPD-specific patient reported outcomes, health status, dyspnoea and respiratory symptoms? An observational study in a working population.

OBJECTIVES: We hypothesised that chronic obstructive pulmonary disease (COPD)-specific health status measured by the COPD assessment test (CAT), respiratory symptoms by the evaluating respiratory symptoms in COPD (E-RS) and dyspnoea by Dyspnoea-12 (D-12) are independently based on specific conceptual frameworks and are not interchangeable. We aimed to discover whether health status, dyspnoea or respiratory symptoms could be related to smoking status and airflow limitation in a working population. DESIGN: This is an observational, cross-sectional study. PARTICIPANTS: 1566 healthy industrial workers were analysed. RESULTS: Relationships between D-12, CAT and E-RS total were statistically significant but weak (Spearman's correlation coefficient=0.274 to 0.446). In 646 healthy non-smoking subjects, as the reference scores for healthy non-smoking subjects, that is, upper threshold, the bootstrap 95th percentile values were 1.00 for D-12, 9.88 for CAT and 4.44 for E-RS. Of the 1566 workers, 85 (5.4%) were diagnosed with COPD using the fixed ratio of the forced expiratory volume in one second/forced vital capacity <0.7, and 34 (2.2%) using the lower limit of normal. The CAT and E-RS total were significantly worse in non-COPD smokers and subjects with COPD than non-COPD never smokers, although the D-12 was not as sensitive. There were no significant differences between non-COPD smokers and subjects with COPD on any of the measures. CONCLUSIONS: Assessment of health status and respiratory symptoms would be preferable to dyspnoea in view of smoking status and airflow limitation in a working population. However, these patient-reported measures were inadequate in differentiating between smokers and subjects with COPD identified by spirometry.

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.

The COPD assessment test and St George's Respiratory Questionnaire: are they equivalent in subjects with COPD?

BACKGROUND: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD. However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George's Respiratory Questionnaire (SGRQ). This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire. METHODS: A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study. Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ. RESULTS: Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach's α coefficients =0.890 and 0.933). Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P<0.001). Correlations of CAT scores with parameters related to pulmonary function, dyspnea, exercise performance, and psychological factors were inferior to correlations with those parameters with SGRQ total scores. Both multiple regression analyses and principal component analyses revealed that there were slight differences between SGRQ total scores and CAT scores. CONCLUSION: The CAT is similar to SGRQ in terms of discriminating health status. However, we demonstrated that what is assessed by the CAT may differ slightly from what is measured by SGRQ.

COPD and disease-specific health status in a working population.

BACKGROUND: It has been debated whether treatment should be started early in subjects with mild to moderate COPD. An impaired health status score was associated with a higher probability of being diagnosed with COPD as compared with undiagnosed COPD. PURPOSE: To investigate the health status in a healthy working population, to determine reference scores for healthy non-smoking subjects, and to investigate the relationship between their health status and airflow limitation. METHODS: A total of 1333 healthy industrial workers aged ≥40 years performed spirometry and completed the St. George's Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). RESULTS: The prevalence of COPD defined by the fixed ratio of the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 10.9%, and the prevalence defined by the Lower Limit of Normal was 5.0%. All SGRQ and CAT scores were skewed to the milder end. In 512 non-smoking subjects with normal spirometry, the mean SGRQ score was 5.7, and the mean CAT score was 5.8. In 145 people with COPD defined by the fixed ratio, the mean SGRQ score was 7.9, with a zero score in 6.9% of the subjects. Using the CAT, the mean score was 7.3, with 7.6% of the scores being zero. The scores in patients identified using the Lower Limit of Normal approach were: SGRQ 8.4 (13.4% had a score of zero) and CAT 7.4 (13.4% had a score of zero). Although the 95th percentiles of the Total, Symptoms, Activity, and Impact scores of the SGRQ and CAT sores were 13.8, 34.0, 23.4, 7.2 and 13.6 in the 512 healthy non-smoking subjects, respectively, they were also distributed under their upper limits in over 80% of the COPD subjects. CONCLUSION: The COPD-specific health status scores in a working population were good, even in those with spirometrically diagnosed COPD. All scores were widely distributed in both healthy non-smoking subjects and in subjects with COPD, and the score distribution overlapped remarkably between these two groups. This suggests that symptom-based methods are not suitable screening tools in a healthy general population.

Case identification of subjects with airflow limitations using the handheld spirometer "Hi-Checker™" : comparison against an electronic desktop spirometer.

BACKGROUND: Systematic case identification has been proposed as a strategy to improve diagnosis rates and to enable the early detection of subjects with COPD. We hypothesized that case identification could be possible using the handheld spirometer Hi-Checker™. AIM: To determine how to modify the FEV(1)/FEV(6) values obtained using the Hi-Checker™ to screen for cases with airflow limitation. METHODS: Spirometry was performed with both an electronic desktop spirometer and with the Hi-Checker™ in 312 male subjects. RESULTS: The average FEV(1) (mean ± SD) measured using a conventional spirometer and the Hi-Checker™ was 2.99 ± 0.56L and 3.07 ± 0.57L, respectively. These results were significantly different (P<0.001, paired t-test for both). This difference of -0.08 ± 0.13L (95% confidence interval: -0.094-0.066L) was normally distributed, and thought to be random. Statistically significant correlations were found for all measurements between the spirometer and the Hi-Checker™ ; the Pearson's correlation coefficient (R) between the FEV(1)/FVC and FEV(1)/FEV(6) values was 0.881. If one defines a FEV(1/)FVC smaller than 0.7 measured by the spirometer as airflow limitation, then a FEV(1)/FEV(6) smaller than 0.746 measured by the Hi-Checker™ best matches this definition, and Cohen's kappa coefficient was 0.672. CONCLUSION: Although the Hi-Checker™ estimates resembled those from conventional spirometry, it should be emphasized that the two methods did not produce identical results due to random measurement error. Although one must be careful about overinterpreting these results, since the Hi-Checker™ is small and inexpensive, it could make a significant contribution in facilitating the case selection of patients with airflow limitation.