The Effect of Lung Volume Reduction Surgery on Chronic Obstructive Pulmonary Disease Exacerbations

Rationale: Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known

Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema

BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean +/- SE improvement in FEV1 (15.2 +/- 3.1%), St. George's Respiratory Questionnaire (-12 +/- 2 points), and residual volume (-0.57 +/- 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume >= 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (<20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes

Machine Learning Characterization of COPD Subtypes: Insights From the COPDGene Study

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.N

Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort.

RationaleSome COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.ObjectiveTo define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.MethodsWe analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).MeasurementsWe defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire &lt;5; 6-minute walking distance &lt;250 m; St George's Respiratory Questionnaire activity domain &gt;60; COPD Assessment Test &gt;20; fatigue (FACIT-F Trial Outcome Index) &lt;50; SF-12 &lt;20.ResultsUsing these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P&lt;0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point -1.0 reliably identified disability. This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.ConclusionOur novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD

Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort.

RationaleSome COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.ObjectiveTo define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.MethodsWe analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).MeasurementsWe defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire &lt;5; 6-minute walking distance &lt;250 m; St George's Respiratory Questionnaire activity domain &gt;60; COPD Assessment Test &gt;20; fatigue (FACIT-F Trial Outcome Index) &lt;50; SF-12 &lt;20.ResultsUsing these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P&lt;0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point -1.0 reliably identified disability. This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.ConclusionOur novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD