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One of the characteristics of severe emphysema is hyperinflation of regions of the lungs. In this trial, valves that prevented air entry but allowed air to escape were placed in lobar airways. Patients receiving endobronchial valves had modest improvements in lung function and exercise performance. Emphysema is a leading cause of disability and death. Lung-volume–reduction surgery, in which selected areas of hyperinflated lungs are resected, improves exercise tolerance and prolongs life in selected patients. However, concern regarding the risk of perioperative death and complications contributes to underutilization. 1 – 4 Less invasive bronchoscopic techniques that are based on the presumed physiological effects of lung-volume–reduction surgery have been developed. 5 – 10 Early uncontrolled trials using unidirectional valves placed in selected lung airways to block regional inflation while allowing exhalation have reported improvements in lung function and symptoms with modest risk, including distal pneumonia or pneumothorax. 5 , 6 , 9 , 11 – . . .

Abstract Rationale Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. Objectives In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. Methods Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8–0.9 and 0.7–0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. Measurements and Main Results Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = −0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. Conclusions FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA). We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis. A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23). RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer.

Abstract Rationale Limited data on sex differences in advanced COPD are available. Objectives To compare male and female emphysema patients with severe disease. Methods One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dlco and arterial Po2, higher arterial Pco2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.

BackgroundEmphysema and small airway disease both contribute to chronic obstructive pulmonary disease (COPD), a disease characterised by accelerated decline in lung function. The association between the extent of emphysema in male current and former smokers and lung function decline was investigated.MethodsCurrent and former heavy smokers participating in a lung cancer screening trial were recruited to the study and all underwent CT. Spirometry was performed at baseline and at 3-year follow-up. The 15th percentile (Perc15) was used to assess the severity of emphysema.Results2085 men of mean age 59.8 years participated in the study. Mean (SD) baseline Perc15 was −934.9 (19.5) HU. A lower Perc15 value correlated with a lower forced expiratory volume in 1 s (FEV1) at baseline (r=0.12, p<0.001). Linear mixed model analysis showed that a lower Perc15 was significantly related to a greater decline in FEV1 after follow-up (p<0.001). Participants without baseline airway obstruction who developed it after follow-up had significantly lower mean (SD) Perc15 values at baseline than those who did not develop obstruction (−934.2 (17.1) HU vs −930.2 (19.7) HU, p<0.001).ConclusionGreater baseline severity of CT-detected emphysema is related to lower baseline lung function and greater rates of lung function decline, even in those without airway obstruction. CT-detected emphysema aids in identifying non-obstructed male smokers who will develop airflow obstruction.

Abstract Rationale Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. Objectives We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. Methods In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm2 (CSA<5) and 5 to 10 mm2 (CSA5−10), and calculated the percentage of total CSA for the lung area (%CSA<5 and %CSA5–10, respectively). The correlations of %CSA<5 and %CSA5–10 with pulmonary arterial mean pressure (Ppa¯) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa¯ as the dependent outcome was also performed. Measurements and Main Results The %CSA<5 had a significant negative correlation with Ppa¯ (r = −0.512, P < 0.0001), whereas the correlation between %CSA5–10 and Ppa¯ did not reach statistical significance (r = −0.196, P = 0.083). Multiple linear regression analysis showed that %CSA<5 and diffusing capacity of carbon monoxide (DlCO) % predicted were independent predictors of Ppa¯ (r2 = 0.541): %CSA <5 (P < 0.0001), and DlCO % predicted (P = 0.022). Conclusions The %CSA<5 measured on CT images is significantly correlated to Ppa¯ in severe emphysema and can estimate the degree of pulmonary hypertension.

Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.

Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking. The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5), emphysema (OR = 1.9, 95% CI = 1.4-2.8), or COPD (OR = 2.5, 95% CI = 2.0-3.1). Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78). These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis.

Objectives: To assess the efficiency and safety of endobronchial valve (EBV) treatment in Chinese patients. Methods: A retrospective analysis was performed in patients with chronic obstructive pulmonary disease who underwent EBV implantation in our hospital between October 2010 and January 2017. All patients were confirmed with no collateral ventilation (CV-) or with low airflow (LF) in the treated lobe. Pulmonary function parameters, the 6-minute walk distance (6MWD), the modified Medical Research Council (mMRC), as well as adverse events in the follow-up period were recorded. Results: Thirty-eight advanced emphysema patients received EBV implantation. Significant improvements were found in forced expiratory volume in 1 second ([FEV.sub.1])([FEV.sub.1]: +0.12 L), 6MWD (+64.9 m), and mMRC (-0.5 points). A total of 55.3% and 65.8% of subjects met the score for the minimal clinically important difference in [FEV.sub.1] and 6MWD, respectively. [FEV.sub.1] improved more significantly in the CV- group than in the LF group. Pneumothorax or death did not occur during the follow-up period. Conclusion: Endobronchial valve treatment in patients with advanced emphysema and CV- provides clinically meaningful benefits with a low incidence of pneumothorax. The efficiency and safety of EBV therapy are acceptable in China. Keywords: endobronchial valve, emphysema, bronchoscopic lung volume reduction