Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.
The goal ...of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.
Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders.
In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 P < .001; St. George’s Respiratory Questionnaire, 1.67 P < .001; Medical Outcomes Study Short Form 36 Physical Function, –0.89 P < .001), exercise performance (6-min walk distance, –45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).
Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.
This large trial involving patients with chronic obstructive pulmonary disease examined the relative safety of tiotropium inhalation delivered by two different devices. No significant differences in ...mortality were noted between the two devices.
Tiotropium (Spiriva, Boehringer Ingelheim), a long-acting inhaled anticholinergic bronchodilator, improves lung function, quality of life, and exercise endurance and reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD).
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Tiotropium is approved and marketed as a dry-powder formulation delivered by means of the HandiHaler inhalation device (at a dose of 18 μg)
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and as an aqueous solution delivered by means of the Respimat inhaler (at a dose of 5 μg) in many countries.
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Crossover trials of tiotropium Respimat at a dose of 5 μg and HandiHaler at a dose of 18 μg for up to 4 weeks have shown . . .
Checkley et al discuss the relevance of population-based cohorts in respiratory epidemiology in the era of big data. Cohort studies have been instrumental in understanding respiratory epidemiology ...and identifying risk factors for lung function decline and chronic obstructive pulmonary disease (COPD). Despite the challenges of long-term follow-up and costs, cohort studies starting in early childhood, such as the Tasmanian Longitudinal Health Study (TAHS), provide valuable insights into COPD risk factors and lung function trajectories. The TAHS cohort, publicly accessible and extensively studied, has contributed to our understanding of chronic lung diseases.
Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension (PAH), the minimal important difference (MID) of the 6-minute walk test (6MWT) has not been ...well defined for this population of patients.
To estimate the MID in the 6MWT in patients with PAH.
Study subjects from the clinical trial of tadalafil in PAH, a 16-week, parallel-group, randomized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist, were eligible. 6MWT was performed using a standardized protocol. Distributional and anchor-based methods were used to estimate the MID; the latter method used the Physical Component Summary Score (PCS) of the Medical Outcomes Study 36-item short form (SF-36).
Four hundred five subjects were analyzed. Domains of the SF-36 were weakly to modestly associated with 6MWT. Change in the PCS of the SF-36 was most strongly associated with change in 6MWT (r = 0.40, P < 0.001) and thus was selected as the anchor for subsequent anchor-based analyses. Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m, whereas anchor-based analyses yielded an estimate of 38.6 m.
Using both distributional and anchor-based methods, the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implications for (1) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy, and (2) sample size calculations for future study design.
The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — ...was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.
COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a ...transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).
This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.
Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels.
Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.
Clinicaltrials.gov: NCT01335971.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Comorbidities impact a large proportion of patients with chronic obstructive pulmonary disease (COPD), with over 80% of patients with COPD estimated to have at least one comorbid chronic condition. ...Guidelines for the treatment of COPD are just now incorporating comorbidities to their management recommendations of COPD, and it is becoming increasingly clear that multimorbidity as well as specific comorbidities have strong associations with mortality and clinical outcomes in COPD, including dyspnea, exercise capacity, quality of life, healthcare utilization, and exacerbation risk. Appropriately, there has been an increased focus upon describing the burden of comorbidity in the COPD population and incorporating this information into existing efforts to better understand the clinical and phenotypic heterogeneity of this group. In this article, we summarize existing knowledge about comorbidity burden and specific comorbidities in COPD, focusing on prevalence estimates, association with outcomes, and existing knowledge about treatment strategies.
Background Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are ...limited. Objective We sought to compare subjective and objective measurements of children’s adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes. Methods In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers, adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were randomly assigned to 200 μg of inhaled budesonide twice per day (n = 84) or placebo (n = 56) for 4 years. The κ statistic was used to evaluate agreement between self-reported adherence (daily diary cards) and objectively measured adherence (number of doses left in study inhalers). Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes. Results Adherence of less than 80% was seen in 75% of 140 children when adherence was measured objectively but only in 6% of children when measured by means of self-report. There was poor agreement between objective and subjective measurements of adherence of at least 80% (κ = 0.00; 95% CI, −0.05 to 0.04); self-reported adherence over the 4-year period generally overestimated objectively measured adherence (93.6% vs 60.8%, P < .0001). There was little evidence to indicate that adherence modified treatment-related differences in outcomes. Conclusion Researchers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment.
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