Compared with obstructive spirometry, PRISm is a scarcely studied physiological condition, so the report in this issue of the Journal (pp. 1397-1405) by Wan and colleagues (1) from the COPDGene Study ...(Genetic Epidemiology of Chronic Obstructive Pulmonary Disease COPD) is particularly welcome, because longitudinal studies on this topic are few (2-4) and have not examined the longitudinal transition to and from PRISm, risk factors, and mortality of this subgroup. Furthermore, more than 20% of those fulfilling the criteria of PRISm at study entry increased their lung function during the 5-year follow-up period, a result also seen in the ECLIPSE (Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints) COPD cohort (13). ...it would help to know in those who appeared to progress to obstruction whether they had more small airway disease assessed objectively by parametric response mapping, a measurement already available in this population (15). Longitudinal studies of samples representative of the general population are warranted to verify the COPDGene Study results, and such studies would probably provide even more information about phenotypes of PRISm and their long-term progression. ...those data are available, caution should be observed when interpreting PRISm in a smoker as a form of COPD, at least when based on a single measurement. ?
An extensive clinical trial program supports the efficacy and safety of tiotropium/olodaterol in chronic obstructive pulmonary disease (COPD). We examined the safety of tiotropium/olodaterol compared ...with tiotropium in a large population of patients, focusing on cardiovascular and respiratory events.
Patients (n = 9942) who received once-daily tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (via Respimat®) in TONADO 1 & 2 and DYNAGITO were included. The number of patients and exposure-adjusted rate of events are presented for adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and cardiovascular and respiratory events.
Fewer patients discontinued due to AEs with tiotropium/olodaterol (5.9%) versus tiotropium (7.9%; rate ratio RR 0.72; 95% confidence interval CI 0.62–0.84). There was no significant difference in the incidence of AEs, SAEs, cardiovascular AEs or central nervous system vascular AEs between treatments. Incidences of major adverse cardiovascular events (MACE) were 2.11 per 100 patient-years with tiotropium/olodaterol and 2.22 with tiotropium (RR 0.95; 95% CI 0.72–1.25), and incidences of fatal MACE (including death with undetermined cause) were 0.91 and 1.00 per 100 patient-years with tiotropium/olodaterol and tiotropium, respectively (RR 0.91; 95% CI 0.60–1.37). Respiratory AEs were generally balanced between treatment groups.
These results provide robust evidence that the benefits of tiotropium/olodaterol versus tiotropium are not at the expense of an increased risk of safety events. The combination is a suitable option for patients with COPD, even in the presence of cardiovascular risk factors.
clinicaltrials. gov (TONADO 1 and 2: NCT01431274, NCT01431287; DYNAGITO: NCT02296138).
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Crim et al discuss their randomized double-blined clinical trial on pulse wave velocity in chronic obstructive pulmonary disease (COPD) and the impact of inhaled therapy. Patients with COPD are at ...increased risk for cardiovascular disease (CVD). Those with moderate airflow limitation are more likely to die of CVD than to die of respiratory failure. Arterial pulse wave velocity (aPWV), a vascular stiffness marker, is ail independent predictor of CVD risk that is known to be elevated in patients with COPD. Reduced arterial elasticity plays a direct pathologic role in promoting CVD events. Therefore, decreasing aPWV should lessen future morbidity and mortality.
Recent studies report a lower mortality rate during treatment with long-acting muscarinic antagonist (LAMA)/long-acting β
-agonist (LABA)/inhaled corticosteroid (ICS) versus LAMA/LABA in patients ...with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations.
We compared time to all-cause mortality with LAMA/LABA versus LAMA/LABA/ICS in patients with mild-to-very-severe COPD and a predominantly low exacerbation risk.
Data were pooled from six randomized controlled trials (TONADO 1/2, DYNAGITO, WISDOM, UPLIFT and TIOSPIR; LAMA/LABA: n = 3156, LAMA/LABA/ICS: n = 11,891). Analysis was on-treatment and data were censored at 52 weeks. Patients on LAMA/LABA/ICS received ICS prior to study entry, which was not withdrawn at randomization. Patients on LAMA/LABA/ICS were propensity score (PS)-matched to patients on LAMA/LABA who had not previously received ICS; covariates included age, sex, geographical region, smoking status, post-bronchodilator forced expiratory volume in 1 second percent predicted, exacerbation history in previous year, body mass index and time since diagnosis. Time to all-cause mortality was assessed using Cox proportional hazard regression models.
After PS matching, 3133 patients on LAMA/LABA and 3133 patients on LAMA/LABA/ICS were analyzed. Fewer than 20% of patients reported ≥2 exacerbations in the prior year (LAMA/LABA: 19.1%; LAMA/LABA/ICS: 19.0%). There were 41 (1.3%) deaths on LAMA/LABA and 45 (1.4%) deaths on LAMA/LABA/ICS. No statistically significant difference in time to death was observed between treatment arms (hazard ratio for LAMA/LABA 1.06; 95% confidence intervals 0.68, 1.64; P = 0.806). Sensitivity analyses conducted using different covariates or in an intent-to-treat population showed similar results.
This pooled analysis of over 6000 patients with mild-to-very-severe COPD and predominantly low exacerbation risk showed no differences in mortality with LAMA/LABA versus LAMA/LABA/ICS, suggesting that the survival benefit of triple therapy seen in some recent studies may be specific to a high-risk population. This supports current Global Initiative for Chronic Obstructive Lung Disease recommendations that triple therapy should be reserved for the subpopulations of patients who need it the most (eg, those with an eosinophilic phenotype and a high risk of exacerbations) to avoid ICS overuse.
Summary Long-acting bronchodilators in combination with inhaled corticosteroids (ICS) are recommended to decrease the risk of recurrent exacerbations in patients with Global initiative for chronic ...Obstructive Lung Disease (GOLD) stage 3–4 chronic obstructive pulmonary disease (COPD). There is increasing concern about the clinical benefit and long-term safety of ICS use in COPD patients. The WISDOM (Withdrawal of Inhaled Steroids During Optimised bronchodilator Management) study ( NCT00975195 ) aims to evaluate the need for ICS use via stepwise withdrawal of ICS in COPD patients (GOLD 3–4 with a history of at least one exacerbation during the 12-month period prior to screening) receiving dual bronchodilation. During the 6-week run-in period, 2456 patients receive tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily. In a randomized, double-blind, parallel-group, active-controlled fashion, one group of patients continues to receive tiotropium, salmeterol and fluticasone, while the second group initiates stepwise withdrawal of fluticasone. The primary end point is time to first moderate or severe exacerbation following randomized treatment over 52 weeks. Lung function, symptoms and safety are also assessed. A sub-study aims to identify sub-populations and markers of steroid need. This study will determine the benefit of continued ICS therapy in combination with dual long-acting bronchodilators in COPD.
Abstract Exercise-induced oxygen desaturation (EID) is related to mortality in patients with chronic obstructive pulmonary disease (COPD). We investigated: (1) the prevalence of EID; (2) the ...relative-weight of several physiological determinants of EID including pulmonary emphysema, and (3) the relationship of EID with certain patients' clinical characteristics. Data from 2050 COPD patients (age: 63.3 ± 7.1years; FEV1 : 48.7 ± 15.7%pred.) were analyzed. The occurrence of EID (SpO2 post ≤88%) at the six-minute walking test (6MWT) was investigated in association with emphysema quantified by computed-tomography (QCT), and several clinical characteristics. 435 patients (21%) exhibited EID. Subjects with EID had more QCT-emphysema, lower exercise capacity and worse health-status (BODE, ADO indexes) compared to non-EID. Determinant of EID were obesity (BMI≥30 kg/m2 ), impaired FEV1 (≤44%pred.), moderate or worse emphysema, and low SpO2 at rest (≤93%). Linear regression indicated that each 1-point increase on the ADO-score independently elevates odds ratio (≤1.5fold) for EID. About one in five COPD patients in the ECLIPSE cohort present EID. Advanced emphysema is associated with EID. In addition, obesity, severe airflow limitation, and low resting oxygen saturation increase the risk for EID. Patients with EID in GOLD stage II have higher odds to have moderate or worse emphysema compared those with EID in GOLD stage III-IV. Emphysematous patients with high ADO-score should be monitored for EID.
Inhaled corticosteroids (ICS) and long-acting β-agonists (LABA) are frequently used in patients with chronic obstructive pulmonary disease (COPD). Combination treatment with ICS/LABA improves lung ...function and quality of life, and reduces exacerbation frequency compared to treatment with either ICS or LABA alone. Although it is presumed that continued cigarette smoking impairs acute responses to these medications in patients with COPD, there is little direct evidence to support this view. Studies of ICS use in asthma have shown less short-term improvement in lung function and reduced anti-inflammatory effects in active smokers compared to non-smokers 1, 2. Although similar effects are plausible in COPD, they have not been definitively demonstrated. We hypothesised that former smokers with COPD would have greater short- and long-term changes in lung function, respiratory-related quality of life, and exacerbation risk, in response to ICS than continuing and intermittent smokers.
In patients with severe COPD receiving inhaled glucocorticoids and two classes of long-acting bronchodilators, glucocorticoid withdrawal was noninferior to continuation with respect to exacerbations ...but was associated with a slight worsening in lung function and symptoms.
Exacerbations of chronic obstructive pulmonary disease (COPD) are symptomatically defined, acute events that lead to a change in treatment
1
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and are associated with an accelerated decline in lung function and health status.
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Treatment with inhaled glucocorticoids reduces the exacerbation rate, especially when the drugs are used in combination with a long-acting β-agonist (LABA).
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Consequently, combination therapy with an inhaled glucocorticoid and a LABA is recommended in patients with severe COPD or a history of frequent exacerbations.
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Long-acting muscarinic antagonists (LAMAs) have also been shown to prevent exacerbations.
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However, in patients with severe or very severe COPD and . . .
Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, ...or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.
1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.
Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.
No parameter clearly predicts an imminent change in exacerbation frequency category.
SCO104960, clinicaltrials.gov identifier NCT00292552.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at ...heightened CVD risk.
The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD. Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta
-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).
Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events, including palpitations and arrhythmias, did not differ by treatment.
In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.
NCT01313676.
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