Antielastin autoimmunity in tobacco smoking-induced emphysema.

Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.

Lung volume reduction surgery: a meta-analysis of randomized clinical trials.

BACKGROUND: Observational studies have suggested that lung volume reduction surgery (LVRS) is superior to optimal medical therapy for selected subsets of patients with advanced emphysema. Randomized clinical trials (RCTs) with the exception of the National Emphysema Treatment Trial (NETT), failed to enroll a sufficient number of patients to provide clinicians and patients with convincing outcome data on the usefulness of LVRS. It was postulated that a meta-analysis of these RCTs (3-12 months' follow up) may provide more compelling information on the value of LVRS in patients with emphysema. METHODS: A comprehensive search of the MEDLINE database between January 1994 and January 2004 for RCTs on LVRS was performed. RESULTS: From a total of eight RCTs on record, six studies (306 patients) with 3- to 12-month follow up were deemed suitable for meta-analysis. Key baseline features of these RCT populations included heterogeneous emphysema, comparable inclusion/exclusion criteria and, in retrospect, low walking capacity as measured by the 6-minute walk distance (6MWD). This profile closely resembles NETT's 'predominantly upper lobe--low exercise tolerance emphysema' cohort. The LVRS arm of the meta-analysis population showed better results than the medical cohort in terms of pulmonary function (FEV(1) p < 0.0001, FVC p < 0.0001, residual volume p < 0.0001, total lung capacity p = 0.004), gas exchange (arterial partial pressure of oxygen p < 0.0001) and exercise capacity (6MWD p = 0.0002). Although information on quality-of-life measures was not sufficiently uniform to qualify for meta-analysis, a survey of available data revealed better results in the surgical than in the medical arms of each RCT. Mortality 6-12 months after random assignment to treatment was similar in the two study arms, suggesting that the operative mortality from LVRS was offset, within months, by deaths in the medical arm. CONCLUSIONS: This meta-analysis showed that a selected subset of patients with advanced, heterogeneous emphysema and low exercise tolerance (6MWD) experienced better outcomes from LVRS than from medical therapy.

Novel method for measuring effects of gas compression on expiratory flow.

During forced vital capacity maneuvers in subjects with expiratory flow limitation, lung volume decreases during expiration both by air flowing out of the lung (i.e., exhaled volume) and by compression of gas within the thorax. As a result, a flow-volume loop generated by using exhaled volume is not representative of the actual flow-volume relationship. We present a novel method to take into account the effects of gas compression on flow and volume in the first second of a forced expiratory maneuver (FEV(1)). In addition to oral and esophageal pressures, we measured flow and volume simultaneously using a volume-displacement plethysmograph and a pneumotachograph in normal subjects and patients with expiratory flow limitation. Expiratory flow vs. plethysmograph volume signals was used to generate a flow-volume loop. Specialized software was developed to estimate FEV(1) corrected for gas compression (NFEV(1)). We measured reproducibility of NFEV(1) in repeated maneuvers within the same session and over a 6-mo interval in patients with chronic obstructive pulmonary disease. Our results demonstrate that NFEV(1) significantly correlated with FEV(1), peak expiratory flow, lung expiratory resistance, and total lung capacity. During intrasession, maneuvers with the highest and lowest FEV(1) showed significant statistical difference in mean FEV(1) (P < 0.005), whereas NFEV(1) from the same maneuvers were not significantly different from each other (P > 0.05). Furthermore, variability of NFEV(1) measurements over 6 mo was <5%. We concluded that our method reliably measures the effect of gas compression on expiratory flow.