An Observational Study Assessing Changes in Health and Functional Status in Patients with Chronic Obstructive Pulmonary Disease (COPD) During Therapy with Spiolto® Respimat® in Everyday Clinical Practice: The Greek ELLACTO Study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) often report deteriorated functional status and poor health-related quality of life, both core aspects of their overall health status. The study objective was to assess tiotropium/olodaterol Respimat® effects on health and functional status of COPD patients requiring long-acting dual bronchodilation treatment in the real world. METHODS: ELLACTO was an open-label, observational, prospective study conducted in Greece, measuring changes on health and functional status of COPD patients treated with a fixed dose of tiotropium/olodaterol Respimat® for approximately 6 weeks. The primary endpoint was "therapeutic success" defined as a ≥ 0.4-point decrease in the Clinical COPD Questionnaire (CCQ) score at week 6. Secondary endpoints included absolute changes in the CCQ and the functional subscale CCQ-4 at week 6, patient general condition measured by Physician's Global Evaluation (PGE) score at baseline and week 6, patient satisfaction and preference with Respimat® device (assessed by the abbreviated Patient Satisfaction and Preference Questionnaire (PASAPQ)) at week 6 and treatment continuation with tiotropium/olodaterol Respimat® after the study. RESULTS: After approximately 6 weeks of treatment with tiotropium/olodaterol Respimat®, therapeutic success was achieved by 64.3% of 1332 patients included in the final analysis [95% confidence interval [CI] 62-67]. Mean [standard deviation (SD)] absolute changes in CCQ and CCQ-4 scores at week 6 were - 0.63 (0.635) and - 0.59 (0.714) points, respectively. Patient general condition improved and more than 77.4% of patients were satisfied or very satisfied with the use of the Respimat® device. Among patients previously using the HandiHaler® device (n = 254), 85.4% expressed a preference for Respimat® over 6.7% for HandiHaler®. Most patients (95.7%) were willing to continue treatment with tiotropium/olodaterol Respimat® after the study. CONCLUSIONS: Treatment with tiotropium/olodaterol Respimat® led to an improved health status in Greek COPD patients. Most patients also expressed a preference for the Respimat® device and willingness to continue treatment with it. TRIAL REGISTRATION: ClinicalTrials.gov NCT03419962.

Strategies to improve anxiety and depression in patients with COPD: a mental health perspective.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by progressive and only partially reversible symptoms. Worldwide, the incidence of COPD presents a disturbing continuous increase. Anxiety and depression are remarkably common in COPD patients, but the evidence about optimal approaches for managing psychological comorbidities in COPD remains unclear and largely speculative. Pharmacological treatment based on selective serotonin reuptake inhibitors has almost replaced tricyclic antidepressants. The main psychological intervention is cognitive behavioral therapy. Of particular interest are pulmonary rehabilitation programs, which can reduce anxiety and depressive symptoms in these patients. Although the literature on treating anxiety and depression in patients with COPD is limited, we believe that it points to the implementation of personalized strategies to address their psychopathological comorbidities.

Changes in BODE Quartiles After Pulmonary Rehabilitation Do Not Predict 2-Year Survival in Patients With COPD.

PURPOSE: Pulmonary rehabilitation (PR) has well documented positive effects in patients with chronic obstructive pulmonary disease (COPD). The BODE (body mass index, airflow obstruction, dyspnea, and exercise) index reflects the multicomponent nature of COPD. We aimed to determine whether changes in BODE quartiles after a PR program might affect 2-year survival and which characteristics drive changes in BODE quartiles after PR intervention. METHODS: Ninety-five patients with COPD participated in a PR program. The BODE index and anxiety, depression, and quality of life questionnaires were completed before and after the PR program. Five-year survival was recorded for all patients, irrespective of changes in BODE quartiles. RESULTS: Up to 62% of patients with COPD had an improvement in the BODE index, whereas 42% of patients had a change in BODE quartile. Survival did not differ between patients who did not and who did show an improvement in BODE quartiles, despite a trend in favor of the latter (log-rank P = .202). Similar results were observed for patients who did and did not demonstrate a change in the BODE index ≥2 (log-rank P = .679). Significant changes in BODE quartiles were mainly attributed to the duration of the disease, current smoking status, hospitalization rate in the previous year, and the presence of poorer quality of life, as well as to anxiety and depression at baseline. CONCLUSIONS: Pulmonary rehabilitation significantly influenced the BODE index. The significant changes in BODE quartiles were associated with the duration of the disease, current smoking status, increased hospitalization rate, poorer quality of life, anxiety, and depression at baseline, but failed to predict 2-year survival.

Contribution of psychological factors in dropping out from chronic obstructive pulmonary disease rehabilitation programs.

Significant positive effects, particularly on psychological state in patients who completed the follow-up pulmonary rehabilitation programs, are indicated by a large number of studies. Yet, a remarkable proportion of selected patients drop out from these programs. In this study, we investigated existing differences on psychological variables among COPD patients who complete and those who drop out from pulmonary rehabilitation programs. The study included 144 patients, 43 (29.9%) of whom did not complete the program. SCL-90 was used for the assessment of psychological symptoms. On the SCL-90-R scale 55.6% of patients had abnormal findings. Patients who discontinued the program had higher rates of depression and somatization compared to those who completed it. Regarding the psychopathology scales of SCL-90R, we found that patients who discontinued the program showed higher levels of psychopathology on the scales of somatization, depression, paranoid ideation, and psychotism compared to those who completed the program. The final regression model showed that patients with low educational status and psychotism were more likely to leave the program. In conclusion, psychopathology contributes to patients dropping out from a COPD rehabilitation program; thus, psychological assessment prior to inclusion in rehabilitation programs may reduce dropouts.

A pulmonary rehabilitation program reduces levels of anxiety and depression in COPD patients.

BACKGROUND: The presence of anxiety and depressive symptoms in COPD patients has been acknowledged for many years. The preponderance of recent studies supports the utility of pulmonary rehabilitation programs to reduce the levels of depression and anxiety in these patients. The aim of this study is to investigate possible changes in levels of anxiety and depression among patients enrolled in a pulmonary rehabilitation program, along with the role of disease severity in these changes. METHODS: In 101 COPD patients, who attended a pulmonary rehabilitation program, levels of trait anxiety (STAI) and depressive symptoms (BDI) were assessed at the beginning and at the end of the program. Age, sex, level of education in years and stage of disease severity were recorded. RESULTS: Our study included 80 male and 21 female patients. Mean age and mean education level were 64.1 ± 8.1 and 11.3 ± 4.1 years, respectively. Regarding COPD staging, 11 patients suffered from mild, 16 from moderate, 47 from severe and 27 from very severe COPD. Significant decreases in anxiety (from 39.7 to 34.0, p < 0.001) and depression rates (from 10.7 to 6.3, p < 0.001) were observed. A statistically significant reduction in anxiety and depression was revealed (p < 0.05)at all stages of COPD. CONCLUSION: Pulmonary rehabilitation programs should be offered to all COPD patients irrespective of disease severity, since they all lead to improvement in anxiety and depressive symptoms.

Driving-Related Neuropsychological Performance in Stable COPD Patients.

Background. Cognitive deterioration may impair COPD patient's ability to perform tasks like driving vehicles. We investigated: (a) whether subclinical neuropsychological deficits occur in stable COPD patients with mild hypoxemia (PaO(2) > 55 mmHg), and (b) whether these deficits affect their driving performance. Methods. We recruited 35 stable COPD patients and 10 normal subjects matched for age, IQ, and level of education. All subjects underwent an attention/alertness battery of tests for assessing driving performance based on the Vienna Test System. Pulmonary function tests, arterial blood gases, and dyspnea severity were also recorded. Results. COPD patients performed significantly worse than normal subjects on tests suitable for evaluating driving ability. Therefore, many (22/35) COPD patients were classified as having inadequate driving ability (failure at least in one of the tests), whereas most (8/10) healthy individuals were classified as safe drivers (P = 0.029). PaO(2) and FEV1 were correlated with almost all neuropsychological tests. Conclusions. COPD patients should be warned of the potential danger and risk they face when they drive any kind of vehicle, even when they do not exhibit overt symptoms related to driving inability. This is due to the fact that stable COPD patients may manifest impaired information processing operations.

Psychological symptom patterns and vital exhaustion in outpatients with chronic obstructive pulmonary disease.

BACKGROUND: Several studies have reported high prevalence of anxiety and depression in chronic obstructive pulmonary disease (COPD) outpatients. Moreover, these patients share psychological or psychopathological characteristics that inhibit their ability to cope with the disease. In the present study we aimed to record the prevalence of psychological symptom patterns in a sample of Greek COPD outpatients and to assess which psychological factors (and to which degree) contribute to vital exhaustion (VE). METHODS: The study included 139 COPD outpatients. We used the Symptom Checklist 90 - Revised (SCL-90-R) and the Maastricht Questionnaire (MQ) in order to evaluate psychological symptom patterns and VE, respectively. RESULTS: The mean MQ score was 19.6, which is significantly higher than the corresponding score in the general population. Regarding the SCL-90-R dimensions, depression was the highest followed by somatization, obsessive-compulsive and anxiety dimensions. Additionally, a positive correlation was observed between the MQ and the SCL-90-R dimensions. MQ failed to demonstrate correlation with age, gender, education level or the severity of the disease. Depression seems to be responsible for 57.9% of the variation of VE, while obsessive-compulsiveness is responsible for an additional 2.4%. All the remaining dimensions of SCL-90-R had no statistically significant contributions. CONCLUSIONS: Our findings suggest the high prevalence of VE, together with high rates in most of the SCL-90-R dimensions with greater depression, somatization, obsessive-compulsiveness and anxiety in a Greek COPD group at various Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria stages. The coexistence of such symptoms should be further assessed as an eventual unfavorable prognostic factor.

Pathophysiology of evolution of small airways disease to overt COPD.

BACKGROUND: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; AC(T)) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFL(T)) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. METHODS: In this cross-sectional study we have assessed for the first time the phase III slope, AC(T) and EFL(T) in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. RESULTS: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). AC(T) was absent in smokers with normal spirometry and in most patients with mild COPD. EFL(T) first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. CONCLUSIONS: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV(1)/FVC ratio from GOLD I to IV. A reduction of FEV(1) occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of AC(T). Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.

Prevalence of alexithymia and its association with anxiety and depression in a sample of Greek chronic obstructive pulmonary disease (COPD) outpatients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem, especially in adults over 40 years of age, and has a great social and economic impact. The psychological morbidity of COPD patients with regard to anxiety and depressive symptoms has been extensively studied in the past. However, few studies have investigated the prevalence of alexithymia in these patients, as well as its association with this comorbidity. Based on this fact, we studied the prevalence of alexithymia and its association with anxiety and depressive symptoms in COPD outpatients. METHODS: The present study included 167, randomly selected, outpatients diagnosed with COPD. Alexithymia, anxiety and depression were assessed using the Toronto Alexithymia Scale (TAS-20), Spielberger Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI), respectively. RESULTS: The mean BDI score was 12.88 (SD: 7.7), mean STAI score 41.8 (SD: 11.0) and mean TAS-20 score 48.2 (SD: 11.5). No differences were observed between genders regarding age and alexithymia (t test P > 0.05), while female patients presented higher depression and trait anxiety scores than males (t test P < 0.05). Clinically significant levels of anxiety were present in 37.1% of men, and in 45.7% of women. The mean depression score was also higher than the corresponding mean score in the general population (one-sample t test P < 0.01), while 27.7% and 30.5% of the sample presented mild and moderate to severe depression, respectively. Finally, a strong correlation was observed between alexithymia, depression and anxiety. CONCLUSIONS: This study confirms the high prevalence of anxiety and depression symptoms in Greek outpatients with COPD. The prevalence of alexithymia in COPD patients, contrary to what has been observed in patients with other chronic respiratory diseases, seem to be lower. However, we observed a strong association between alexithymia, depression and anxiety levels. This observation suggests that alexithymia should be taken into consideration when drafting specific psychotherapeutic interventions for these patients.

A phase II study of sequential docetaxel and gemcitabine followed by docetaxel and carboplatin as first-line therapy for non-small cell lung cancer.

Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m(2) was administered and was followed by docetaxel 65 mg/m(2). Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m(2) followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexamethasone. Response rates at three cycles were: 19% achieved a partial response (PR), 46% had stable disease (SD) and 23% had progressive disease. At six cycles, 8% of the patients maintained PR, 19% showed SD and 35% had progressive disease. The median time-to-disease progression was 6 months. The median survival time of patients was 10 months while, at the end of the first year, the patients who managed to get through the complete therapy (20 patients) had a survival rate of 38%. This detailed analysis of 20 patients showed that 80% of the patients survived for up to 6 months, 38% up to 12 months and 19% for more than a year. The only risk factor associated with the hazard of death among the factors studied was the performance status of the patients. Patients with PS=0 presented a median survival time of 13 months and those with PS=1, it was only 9 months. Non-haematological and haematological toxic effects were generally mild to moderate and entirely manageable.

Effects of exercise-induced arterial hypoxaemia and work rate on diaphragmatic fatigue in highly trained endurance athletes.

Diaphragmatic fatigue occurs in highly trained athletes during exhaustive exercise. Since approximately half of them also exhibit exercise-induced arterial hypoxaemia (EIAH) during high-intensity exercise, the present study sought to test the hypothesis that arterial hypoxaemia contributes to exercise-induced diaphragmatic fatigue in this population. Ten cyclists ( : 70.0 +/- 1.6 ml kg(-1) min(-1); mean +/-s.e.m.) completed, in a balanced ordering sequence, one normoxic (end-exercise arterial O(2) saturation (S(a,O(2))): 92 +/- 1%) and one hyperoxic (F(I,O(2)): 0.5% O(2); S(a,O(2)) : 97 +/- 1%) 5 min exercise test at intensities equal to 80 +/- 3 and 90 +/- 3% of maximal work rate (WR(max)), respectively, producing the same tidal volume (V(T)) and breathing frequency (f) throughout exercise. Cervical magnetic stimulation was used to determine reduction in twitch transdiaphragmatic pressure (P(di,tw)) during recovery. Hyperoxic exercise at 90% WR(max) induced significantly (P= 0.022) greater post-exercise reduction in P(di,tw) (15 +/- 2%) than did normoxic exercise at 80% WR(max) (9 +/- 2%), despite the similar mean ventilation (123 +/- 8 and 119 +/- 8 l min(-1), respectively), breathing pattern (V(T): 2.53 +/- 0.05 and 2.61 +/- 0.05 l, f: 49 +/- 2 and 46 +/- 2 breaths min(-1), respectively), mean changes in P(di) during exercise (37.1 +/- 2.4 and 38.2 +/- 2.8 cmH(2)O, respectively) and end-exercise arterial lactate (12.1 +/- 1.4 and 10.8 +/- 1.1 mmol l(-1), respectively). The difference found in diaphragmatic fatigue between the hyperoxic (at higher leg work rate) and the normoxic (at lower leg work rate) tests suggests that neither EIAH nor lactic acidosis per se are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of S(a,O(2)) tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater leg blood flow.

Respiratory kinematics by optoelectronic plethysmography during exercise in men and women.

Gender differences in resting pulmonary function are attributable to the smaller lung volumes in women relative to men. We sought to investigate whether the pattern of response in operational lung volumes during exercise is different between men and women of similar fitness levels. Breath-by-breath volume changes of the entire chest wall ( V(.)( CW)) and its rib cage ( V(.)( Rc)) and abdominal ( V(.)( Ab)) compartments were studied by optoelectronic plethysmography in 15 healthy subjects (10 men) who underwent a symptom-limited ( W (peak)) incremental bicycle test. The pattern of change in end-inspiratory and end-expiratory V(.)( CW) ( V(.)( CW,EI) and V(.)( CW,EE), respectively) did not differ between the sexes. With increasing workload the decrease in V(.)( CW,EE) was almost entirely attributable to a reduction in end-expiratory V(.)( Ab), whereas the increase in V(.)( CW,EI) was due to the increase in end-inspiratory V(.)( Rc) in both sexes. In men, at W (peak) tidal volume [ V(.)( T), 2.7 (0.2) l] and inspiratory capacity [IC, 3.4 (0.2) l] were significantly greater than in women [1.8 (0.2) and 2.6 (0.2) l, respectively]. However, after controlling for lung size using forced vital capacity (FVC) as a surrogate, the differences between men and women were eliminated [ V(.)( T) /FVC 49 (3) and 45 (3) respectively, and IC/FVC 63 (2) and 65 (3) respectively]. All data are presented as mean (SE). In both men and women the contribution of the rib cage compartment to V(.)( T) expansion was significantly greater than that of the abdominal compartment. We conclude that gender differences in operational lung volumes in response to progressive exercise are principally attributable to differences related to lung size, whereas compartmental chest wall kinematics do not differ among sexes.