Comorbidities of patients in tiotropium clinical trials : comparison with observational studies of patients with chronic obstructive pulmonary disease

Acknowledgments The authors are fully responsible for all content and editorial decisions made, were involved at all stages of manuscript development, and have approved the final version for publication. Editorial assistance, supported financially by Boehringer Ingelheim and Pfizer, was provided by Godfrey Lisk of PAREXEL International during the preparation of this manuscript. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited.Peer reviewedPublisher PD

Endoscopic Lung Volume Reduction: An Expert Panel Recommendation

Chronic obstructive pulmonary disease (COPD) is a progressive condition comprising a constellation of disorders from chronic bronchitis, airflow obstruction through to emphysema. The global burden of COPD is estimated at more than 6% of the population. The standard of care is based on a combination of smoking cessation, immunization, pharmacological treatments and pulmonary rehabilitation. However, the more advanced stages of COPD are challenging to manage. In this situation, our current standards of care do not adequately control patient symptoms nor halt the progressive decline. For the emphysema phenotype, lung volume reduction surgery has shown a beneficial effect in selected patients but is counterbalanced by the morbidity experienced by some patients. Bronchoscopic volume reduction technologies have been developed to improve the clinical situation of emphysema patients. This expert statement provides broad guidance regarding patient selection and the current position of the available techniques for patients with advanced emphysema

Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial

Background: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Methods: Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or >= 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. Results: In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and >= 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. Conclusion: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer surviva

Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

Exacerbations; Lung function; TiotropiumExacerbaciones; Función pulmonar; TiotropioExacerbacions; Funció pulmonar; TiotropiIntroduction Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID. Methods Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George’s Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID. Results Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001). Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030). Conclusion In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium. These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy.Support for this project and the journal’s Open Access Fee were funded by Boehringer Ingelheim International GmbH. No Rapid Service Fee was received by the journal for the publication of this article

Reproducibility of exhaled nitric oxide measurements in overweight and obese adults

Exhaled nitric oxide is a noninvasive measure of airway inflammation that can be detected by a handheld device. Obesity may influence the reproducibility of exhaled nitric oxide measurements, by - for instance - decreased expiratory reserve volume. We analyzed triple exhaled nitric oxide measurements from 553 participants (aged 45 to 65 years with a body mass index ≥27 kg/m2) of the Netherlands Epidemiology of Obesity Study. The interclass correlation coefficient (single measurement reliability) was 0.965 (95% CI: 0.960, 0.970). We conclude that for assessment of exhaled nitric oxide in large cohorts of overweight and obese adults a single measurement suffice

Effects of airway obstruction and hyperinflation on electrocardiographic axes in COPD

Background: COPD influences cardiac function and morphology. Changes of the electrical heart axes have been largely attributed to a supposed increased right heart load in the past, whereas a potential involvement of the left heart has not been sufficiently addressed. It is not known to which extent these alterations are due to changes in lung function parameters. We therefore quantified the relationship between airway obstruction, lung hyperinflation, several echo- and electrocardiographic parameters on the orientation of the electrocardiographic (ECG) P, QRS and T wave axis in COPD. Methods: Data from the COPD cohort COSYCONET were analyzed, using forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), left ventricular (LV) mass, and ECG data. Results: One thousand, one hundred and ninety-five patients fulfilled the inclusion criteria (mean ± SD age: 63.9 ± 8.4 years; GOLD 0–4: 175/107/468/363/82). Left ventricular (LV) mass decreased from GOLD grades 1–4 (p = 0.002), whereas no differences in right ventricular wall thickness were observed. All three ECG axes were significantly associated with FEV1 and FRC. The QRS axes according to GOLD grades 0–4 were (mean ± SD): 26.2° ± 37.5°, 27.0° ± 37.7°, 31.7° ± 42.5°, 46.6° ± 42.2°, 47.4° ± 49.4°. Effects of lung function resulted in a clockwise rotation of the axes by 25°-30° in COPD with severe airway disease. There were additional associations with BMI, diastolic blood pressure, RR interval, QT duration and LV mass. Conclusion: Significant clockwise rotations of the electrical axes as a function of airway obstruction and lung hyperinflation were shown. The changes are likely to result from both a change of the anatomical orientation of the heart within the thoracic cavity and a reduced LV mass in COPD. The influences on the electrical axes reach an extent that could bias the ECG interpretation. The magnitude of lung function impairment should be taken into account to uncover other cardiac disease and to prevent misdiagnosis

Sexuality in patients with asthma and COPD

SummarySexual quality of life was examined in 55 outpatients with chronic obstructive pulmonary disease (COPD) and asthma, using disease-specific questionnaires. Compared to an age- and sex-matched norm group, male patients with COPD reported a significantly lower sexual quality of life on all dimensions of the questionnaire. Female patients with COPD reported a lower frequency of sexual intimacy and lower sexual quality of life overall. Patients with asthma reported sexual quality-of-life scores that were somewhat better than COPD patients but worse than the healthy control group. Patients reported that they did not discuss sexual quality-of-life issues with their physician. Sexuality needs to be discussed by the health care provider in the consultation in order to improve quality of life of patients with chronic respiratory disorders

Prognosis and longitudinal changes of physical activity in idiopathic pulmonary fibrosis

Background: Physical activity (PA) is associated with disease severity in idiopathic pulmonary fibrosis (IPF), but longitudinal studies evaluating its prognostic value and changes over time are lacking. Methods: We measured PA (steps per day, SPD) in a cohort of 46 IPF-patients (mean age, 67 years; mean FVC, 76.1%pred.) by accelerometry at baseline, recorded survival status during 3 years follow-up and repeated measurements in survivors. We compared the prognostic value of PA to established mortality predictors including lung function (FVC, DLCO) and 6-min walking-distance (6MWD). Results: During follow-up (median 34 months) 20 patients (43%) died. SPD and FVC best identified non-survivors (AUROC-curve 0.79, p < 0.01). After adjustment for confounders (sex, age, therapy), a standardized increase (i.e. one SD) in SPD, FVC%pred. or DLCO%pred. was associated with a more than halved risk of death (HR < 0.50; p < 0.01). Compared to baseline, SPD, FVC, and 6MWD annually declined in survivors by 973 SPD, 130 ml and 9 m, resulting in relative declines of 48.3% (p < 0.001), 13.3% (p < 0.001) and 7.8% (p = 0.055), respectively. Conclusion: While PA predicts mortality of IPF patients similar to established functional measures, longitudinal decline of PA seems to be disproportionally large. Our data suggest that the clinical impact of disease progression could be underestimated by established functional measures