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Effective management of dyspnea in chronic obstructive pulmonary disease (COPD) requires a clearer understanding of its underlying mechanisms. This roundtable reviews what is currently known about the neurophysiology of dyspnea with the aim of applying this knowledge to the clinical setting. Dyspnea is not a single sensation, having multiple qualitative descriptors. Primary sources of dyspnea include: (1) inputs from multiple somatic proprioceptive and bronchopulmonary afferents, and (2) centrally generated signals related to inspiratory motor command output or effort. Respiratory disruption that causes a mismatch between medullary respiratory motor discharge and peripheral mechanosensor afferent feedback gives rise to a distressing urge to breathe which is independent of muscular effort. Recent brain imaging studies have shown increased limbic system activation in response to various dyspneogenic stimuli and emphasize the affective dimension of this symptom. All of these mechanisms are likely instrumental in exertional dyspnea causation in COPD. Increased central motor drive (and effort) is required to increase ventilation during activity because the inspiratory muscles become acutely overloaded and functionally weakened. Abnormal dynamic ventilatory mechanics and excessive chemostimulation during exercise also result in a widening disparity between escalating central neural drive and restricted thoracic volume displacement. This neuromechanical uncoupling may form the basis for the distressing sensation of unsatisfied inspiration. Interventions that alleviate dyspnea in COPD do so by improving ventilatory mechanics, reducing central neural drive, or both-thereby partially restoring neuromechanical coupling of the respiratory system. Self-management strategies address the affective aspect of dyspnea and are essential to successful treatment.

This ACCORD I study (AClidinium in Chronic Obstructive Respiratory Disease I) was registered on clinicaltrials.gov (NCT00891462) as "Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)".

Both unilateral and bilateral lung volume reduction procedures are being advocated for treatment of severe, generalized emphysema. We analyzed the results of 166 consecutive patients who underwent unilateral (n = 87) or bilateral (n = 79) thoracoscopic stapled lung volume reductions to help define the role for these procedures. There was no statistically significant difference in the operative mortality (3.5% vs 2.5%), mean length of stay (11.4 +/- 1 vs 10.9 +/- 1 days), or morbidity for the unilateral and bilateral groups, respectively (p not significant for all variables). Oxygen dependence was eliminated in 18 (36%) of 50 patients who had unilateral procedures and 30 (68%) of 44 of those who had bilateral procedures (p < 0.01). Prednisone was eliminated for 38 (54%) of 51 unilateral-procedure patients, compared with 30 (85%) of 35 bilateral-procedure patients (p = 0.02). Overall, bilateral procedures produced a mean improvement in the forced expiratory volume in 1 second (FEV1) of 57%, compared with 31% for unilateral reduction procedures (p < 0.01). Our bilateral staple procedure produced a 72.8% mean increase in the FEV1 for patients who had upper lobe emphysema. Especially compromised patients (age > or = 75, with preoperative room air Po2 < or = 50 mm Hg or FEV1 < or = 500 ml) had the same morbidity and operative mortality with unilateral or bilateral procedures, but they had a higher 1-year mortality (17% vs 5%), primarily because of respiratory failure after the unilateral operation (p < .001). Although unilateral staple lung volume reduction may produce an excellent result in a given patient, the bilateral procedure appears to be the procedure of choice, because it provides better overall results at no increased morbidity or mortality compared with the unilateral procedure. The results of bilateral staple lung volume reduction by thoracoscopy appear to be comparable to those of median sternotomy.

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Two procedures (laser bullectomy and lung reduction surgery with staples) are currently available for the surgical treatment of patients with diffuse emphysema. We compared the efficacy of these two surgical approaches in 72 patients, aged 67 +/- 7 years (mean +/- standard deviation), who had diffuse emphysema scored as severe on computed tomography and severe fixed expiratory airflow obstruction. The patients were prospectively randomized to undergo either neodymium:yttrium aluminum garnet contact laser surgery (n = 33) or stapled lung reduction surgery (n = 39) by unilateral thoracoscopy. The operative mortalities were 0% and 2.5%, respectively. No significant differences were noted between the groups (p < 0.05) with respect to operating time, hospital days, or air leakage for more than 7 days. However, a delayed pneumothorax developed in six patients (18%) who had laser treatment (p = 0.005). The operations eliminated dependency on supplemental oxygen in 52% of the laser group and 87.5% of the stapled lung reduction group (p = 0.02). The mean postoperative improvement in the forced expiratory volume in 1 second at 6 months was significantly greater for the patients undergoing the staple technique (32.9% vs 13.4%, p = 0.01) than for the laser treatment group.

The goal of this study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in treated patients with asthma, including response to oral corticosteroids, and correlate these sites with expiratory airflow limitation. In 53 (24 male) patients with asthma, age 43 +/- 23 years (mean +/- SD) and all on inhaled corticosteroids, post 180 microg aerosolized albuterol, FEV(1) was 74 +/- 23% predicted and FEV(1)/FVC was 68 +/- 11%. Exhaled NO at 100 ml/second was 27 +/- 23 ppb (p < 0.001 compared with normal, 12 +/- 15 ppb). Bronchial NO maximal flux was 2.4 +/- 3.1 nl/second (p < 0.001 compared with normal, 0.85 +/- 0.55). Alveolar NO concentration was 7.0 +/- 7.4 ppb (p = 0.01 compared with the normal value, 3.2 +/- 2.0 ppb). There was no significant correlation between FEV(1) % predicted or lung elastic recoil and NO bronchial flux or alveolar concentration. However, there was a weak but significant correlation between NO bronchial flux and alveolar concentration (Spearman r = 0.50, p < 0.001). In 10 subjects with asthma on inhaled corticosteroids, 5 days of 30 mg prednisone resulted in isolated significant decreases in NO alveolar concentration, from 13 +/- 10 to 4 +/- 4 ppb (p = 0.002). Despite treatment, including inhaled corticosteroids, patients with asthma may have ongoing separate airway and alveolar sites of NO inflammation, the latter responsive to oral corticosteroids.