The National Emphysema Treatment Trial (NETT)

Abstract

The National Emphysema Treatment Trial (NETT) was a multicenter prospective randomized controlled trial that compared optimal medical treatment, including pulmonary rehabilitation, with optimal medical treatment plus lung volume reduction surgery (LVRS). It was the largest and most complete collection of patient demographic, clinical, physiological, and radiographic data ever compiled in severe emphysema. NETT investigated the effects of optimal medical management and LVRS on short- and long-term survival, as well as lung function, exercise performance, and quality of life. NETT also provided much information regarding the evaluation and prognosis of severe emphysema; specifically the important negative influences that hyperinflation and small airway disease have on survival. NETT emphasized the importance of addressing nonpulmonary issues such as nutrition, cardiac disease, anxiety, and depression in emphysema. NETT demonstrated that physiological, genomic, and radiographic phenotype can predict patient survival as well as response to treatment. Because the major purpose of NETT was to compare bilateral LVRS with optimal medical treatment in emphysema, patients enrolled into NETT were comprehensively characterized and selected to have a specific window of airflow obstruction and hyperinflation and to lack significant comorbidities. The NETT patient population’s restrictive features offer distinct advantages (well-characterized predominant emphysematous phenotype) and disadvantages (lack of comorbidities and significant chronic bronchitis) that must be considered when interpreting the implications of these results. Herein, we provide a summary of the major NETT findings that provide insight into the evaluation and medical treatment of emphysema.

Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma

“…Although there was no evidence of heterogeneity between the studies contributing to the Asp358Ala variant-COPD analysis, it is notable that the direction of the relationship was the same for all cohorts except for NETT/NAS. The NETT cohort differs from the other COPD cohorts in that only patients with both more severe COPD and emphysema were recruited (37); thus the included participants are likely to represent a more restricted sub-phenotype of COPD compared to the other cohorts. Disease outcomes in the UK Biobank were based on self-reported data which can be susceptible to misclassification.…”

“…A summary of baseline characteristics of the UK Biobank participants by rs2228145 genotype is given in Supplementary Material, Table S5. Summary statistics for the association between rs2228145 (and proxy rs4129267) and the risk of COPD were also available for the COPDGene, the National Emphysema Treatment Trial (NETT)/Normative Aging Study (NAS), and GenKOLS studies (37,46–49). …”

Persistence of circulating endothelial microparticles in COPD despite smoking cessation

“…The observation in the present study that, on average, a fraction of smokers with COPD also have elevated levels of total and apoptotic EMPs is consistent with the discussion of the concept of vascular subphenotypes of COPD by Chandra et al 14 In this context, the data on circulating and apoptotic EMPs support the idea that, while the global concept of COPD as an FEV1-defined disorder is useful for epidemiologic studies and as a paradigm for routine clinical care, it is likely masking the concept that there are several subphenotypes of COPD. [38][39][40][41][42] Consistent with this concept, correlation of the total EMP levels and apoptotic EMP levels with the conventional measures of lung destruction (DLCO and HRCT) was, at best, very weak. This may imply that, while overlapping, each parameter is measuring a somewhat different aspect of the same process and/or that each parameter is assessing a different subpopulation of what is globally referred to as 'lung destruction'.…”

Secondary Pneumothorax from a Surgical Perspective

“…LVRS can improve survival in severe lung emphysema, mainly in the upper lobes localized emphysema, and low-ability exercise patients [17]. The National Emphysema Treatment Trial (NETT) identified four groups of patients [19] on the basis of their postoperative exercise tolerance and their emphysema pattern at the CT scan (Table 1).…”