Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD: A 5-year study.

Pulmonary rehabilitation (PR) brings benefits to patients with chronic obstructive pulmonary disease (COPD). Negative pressure ventilation (NPV) increases ventilation and decreases hyperinflation as well as breathing work in COPD. We evaluated the long-term effects of a hospital-based PR program coupled with NPV support in patients with COPD on clinical outcomes.One hundred twenty-nine patients with COPD were followed up for more than 5 years, with the NPV group (n = 63) receiving the support of NPV (20-30 cm H2O delivery pressure for 60 min) and unsupervised home exercise program of 20 to 30 min daily walk, while the control group (n = 6) only received unsupervised home exercise program. Pulmonary function tests and 6 min walk tests (6MWT) were performed every 3 to 6 months. Emergency room (ER) visits and hospitalization with medical costs were recorded.A significant time-by-group interaction in the yearly decline of forced expiratory volume in 1 s in the control group analyzed by mixed-model repeated-measure analysis was found (P = 0.048). The 6MWT distance of the NPV group was significantly increased during the first 4 years, with the interaction of time and group (P = 0.003), the time alone (P = 0.014), and the quadratic time (P < 0.001) being significant between the 2 groups. ER exacerbations and hospitalizations decreased by 66% (P < 0.0001) and 54% (P < 0.0001) in the NPV group, respectively. Patients on PR program coupled with NPV had a significant reduction of annual medical costs (P = 0.022).Our hospital-based multidisciplinary PR coupled with NPV reduced yearly decline of lung function, exacerbations, and hospitalization rates, and improved walking distance and medical costs in patients with COPD during a 5-year observation.

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 µg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = -0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BACKGROUND: Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. METHODS: To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. RESULTS: Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. CONCLUSIONS: A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).

Matrix metalloproteinase-1 polymorphism (-1607G) and disease severity in non-cystic fibrosis bronchiectasis in Taiwan.

OBJECTIVES: Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. DESIGN: To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. RESULTS: The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p<0.01). Forced expiratory volume in 1 second (FEV1) was decreased in bronchiectasis patients with 1G/1G (1.2±0.1 L, n = 14) and 1G/2G (1.3±0.1 L, n = 66) genotypes compared to the 2G/2G genotype (1.7±0.1 L, n = 33, p<0.01). Six minute walking distance was decreased in bronchiectasis patients with 1G/1G and 1G/2G compared to that of 2G/2G genotype. Disease severity evaluated by HRCT score significantly increased in bronchiectasis patients with 1G/1G and 1G/2G genotypes compared to that of 2G/2G genotype. Bronchiectasis patients with at least one MMP-1 (-1607G) allele showed increased tendency for hospitalization. Serum levels of pro-MMP-1, active MMP-1 and TGF-ß1 were significantly increased in patients with bronchiectasis with 1G/1G and 1G/2G genotype compared with 2G/2G genotype or normal subjects. Under IL-1ß stimulation, peripheral blood monocytes from subjects with 1G/2G or 1G/1G genotype secreted higher levels of TGF-ß1compared to subjects with 2G/2G genotype. CONCLUSION: This is the first report to address the influence of MMP-1 polymorphisms on lung function and airway destruction in non-CF bronchiectasis patients. Bronchiectasis patients with MMP-1(-1607G) polymorphism may be more vulnerable to permanent lung fibrosis or airway destruction due to the enhanced MMP-1 and TGF-ß1 activity. Upregulated MMP-1 activity results in proteolytic destruction of matrix, and leads to subsequent fibrosis.

Association Between Emphysema Score, Six-Minute Walk and Cardiopulmonary Exercise Tests in COPD.

BACKGROUND: High-resolution computed tomography (HRCT) has allowed in detection of airway wall abnormalities and emphysema, whose extent may correlate with the clinical severity of the disease in patients with chronic obstructive pulmonary disease (COPD). Six minute walk test (6MWT) and cardiopulmonary exercise test (CPET) can determine functional status. METHODS: A study was undertaken to investigate whether the extent of emphysema in COPD patients quantitatively confirmed by HRCT scoring was associated with distance walked, inspiratory capacity (IC) changes after exercise, anaerobic threshold of cardiopulmonary exercise and the BODE index (body mass index, airflow obstruction, dyspnea, exercise performance). RESULTS: Seventeen patients with COPD underwent HRCT scanning, 6MWT and CPET. The emphysema score was highly correlated to forced vital capacity (FVC) (r=-0.748, p<0.001), forced expiratory volume in 1 second (FEV1) (r=-0.615, p<0.01), IC post exercise (r=-0.663, p<0.01) and dyspnea score post exercise (r=0.609, p<0.01), but was not associated with the BODE index. The distance walked during 6MWT was inversely correlated to emphysema score (r=-0.557, p<0.05). IC before exercise was highly related to the 6MWT. The change in IC after exercise was associated with the percent decline of oxygen saturation after exercise (r=0.633, p<0.01). Severity of lung emphysema in COPD patients was inversely correlated to VO(2) max (r=-0.514, p<0.05) and anaerobic threshold (r=-0.595, p<0.01) of cardiopulmonary exercise. CONCLUSIONS: These results suggest that COPD associated with emphysema on HRCT is characterized by more severe lung function impairment, greater exercise impairment and cardiopulmonary dysfunction.