Patients with advanced emphysema and severe lung hyperinflation have few treatment options to relieve dyspnea.^1,2 Lung volume reduction surgery has been shown to improve lung function, quality of life, and survival in the subset of patients with advanced, heterogeneous, upper lobe emphysema.³ However, relatively few patients with emphysema undergo lung volume reduction surgery because a minority have an upper lobe–dominant heterogeneous pattern of destruction and postoperative complications can be severe.^3-5 A less invasive bronchoscopic approach targeting patients with heterogeneous emphysema involves segmental airway placement of unidirectional valves resulting in lobar collapse and clinical improvement; however, this approach is still investigational in North America and restricted to patients without interlobar collateral channels.^6-8 Patients with advanced homogeneous emphysema and/or presence of interlobar collateral ventilation have very limited treatment options, essentially lung transplantation or palliative support.

Quiz Ref ID Emphysema, a key component of chronic obstructive pulmonary disease, is characterized by lung tissue inelasticity, air trapping, and hyperinflation, causing dyspnea, exercise limitation, and impaired quality of life. Management of severe emphysema represents a challenge because of limited efficacy of currently available treatments. Lung volume reduction surgery demonstrated improved overall survival and better clinical and functional outcomes, particularly in patients with upper lobe–predominant emphysema and low exercise capacity.^1,2 However, lung volume reduction surgery is associated with significant morbidity and mortality. A number of minimally invasive interventional strategies, including endobronchial valves,^3,4 airway bypass,⁵ biological sealants,⁶ thermal vapor ablation,⁷ and endobronchial coils,^8- 14 have been evaluated. Endobronchial valves showed clinically significant improvements in selected patients with upper lobe–predominant emphysema⁴ and with intact fissures.^3,4

Rationale: Matrix metalloprotease (MMP)-9 is an elastolytic endopeptidase produced by activated macrophages that may be involved in the development of human pulmonary emphysema and could be inhibited with existing compounds. Mouse models have demonstrated that excess MMP-9 production can result in permanent alveolar destruction. Objectives: To determine if MMP-9 causes cigarette smoke–induced emphysema using MMP-9 knockout mice and human samples. Methods: Mouse lungs were analyzed for inflammation and airspace enlargement using a mainstream smoke-exposure model. Human macrophage mRNA was isolated from subjects with emphysema by laser capture microdissection. Human blood monocyte mRNA was isolated from subjects with greater than 30 pack-year smoking history. Human gene expression was determined by quantitative polymerase chain reaction and compared with emphysema severity determined by automated computed tomography analysis. Plasma Clara cell secretory protein and surfactant protein-D were quantified to measure ongoing lung injury. Measurements and Main Results: Mice deficient in MMP-9 develop the same degree of cigarette smoke–induced inflammation and airspace enlargement as strain-matched controls. Macrophages are the predominant source of MMP-9 production in human emphysema specimens and similar quantities of macrophage MMP-9 mRNA is present in areas of lung with and without emphysema. Circulating monocytes produce more MMP-9 in individuals with advanced emphysema severity despite no correlation of MMP-9 with markers of ongoing lung damage. Conclusions: These results suggest that MMP-9 in humans who smoke is similar to smoke-exposed mice, where MMP-9 is present in emphysematous lung but not correlated with the emphysema. To the degree that the mechanisms of emphysema in humans who smoke resemble the mouse model, these data suggest specific inhibition of MMP-9 is unlikely to be an effective therapy for cigarette smoke–induced emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00757120).

Background The lung volume reduction (LVR) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema. We investigated the feasibility, safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema. Methods Patients were treated in 11 centres. Safety was evaluated by recording all adverse events, efficacy by the St George's Respiratory Questionnaire (SGRQ) as primary endpoint, and pulmonary function testing, modified Medical Research Council dyspnoea score (mMRC) and 6-min walk distance (6MWD) up to 12 months after the final treatment. Results Sixty patients (60.9 ± 7.5 years, forced expiratory volume in 1 s (FEV₁) 30.2 ± 6.3% pred) were bronchoscopically treated with coils (55 bilateral, 5 unilateral), with a median of 10 (range 5–15) coils per lobe. Within 30 days post-treatment, seven chronic obstructive pulmonary disease exacerbations (6.1%), six pneumonias (5.2%), four pneumothoraces (3.5%) and one haemoptysis (0.9%) occurred as serious adverse events. At 6 and 12 months, respectively, ΔSGRQ was −12.1±12.9 and −11.1±13.3 points, Δ6MWD was +29.7±74.1 m and +51.4±76 m, ΔFEV₁ was +0.11±0.20 L and +0.11±0.30 L, and ΔRV (residual volume) was −0.65±0.90 L and −0.71±0.81 L (all p<0.01). Post hoc analyses showed significant responses for SGRQ, 6MWD and RV in patients with both heterogeneous and homogeneous emphysema. Conclusions LVR coil treatment results in significant clinical improvements in patients with severe emphysema, with a good safety profile and sustained results for up to 1 year. Trial registration number: NCT01328899.

Dyspnea is very frequent in obese subjects. However, its assessment is complex in clinical practice. The modified Medical Research Council scale (mMRC scale) is largely used in the assessment of dyspnea in chronic respiratory diseases, but has not been validated in obesity. The objectives of this study were to evaluate the use of the mMRC scale in the assessment of dyspnea in obese subjects and to analyze its relationships with the 6-minute walk test (6MWT), lung function and biological parameters.