Serum vitamin D is associated with improved lung function markers but not with prevalence of asthma, emphysema, and chronic bronchitis.

Hypovitaminosis D has been linked to several non-bone diseases. Relation between 25-hydroxyvitamin D [25(OH)D] and lung function and lung diseases has received little attention at the global level. Cross-sectional data from three National Health and Nutrition Examination Surveys, 2007-2008, 2009-2010, and 2011-2012 were used to investigate the relationship between serum 25(OH)D concentrations and lung function makers [forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)] and lung diseases (asthma, emphysema, and chronic bronchitis) with multivariate regression models (n = 11,983; men, 6,010; women, 5,973). Serum 25(OH)D concentrations were directly associated with FVC and FEV1 (P for trend < 0.01). Individuals in the 4th quartile serum 25(OH)D had significantly higher FVC and FEV1 compared to those in the 1st quartile (P < 0.01). When data were stratified based on gender and smoking status, we found similar associations between serum 25(OH)D concentrations and lung function markers. There was no relation between serum 25(OH)D and prevalence of asthma, chronic bronchitis, and emphysema in US adults. Serum 25(OH)D concentration is associated with improved lung function markers but not with the prevalence of asthma, emphysema, and chronic bronchitis. Controlled studies are needed to determine if the vitamin D supplementation improves lung function in adults and in smokers.

Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent ß-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.

Pharmacokinetics and metabolism of all-trans- and 13-cis-retinoic acid in pulmonary emphysema patients.

Retinoids promote lung alveolarization in animal models and were administered to patients as part of the Feasibility of Retinoid Therapy for Emphysema (FORTE) study. This FORTE substudy investigated the pharmacokinetic profiles of 2 retinoic acid isomers-all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13-cRA)-in subjects with emphysema, evaluated strategies to overcome self-induced ATRA catabolism, and identified pharmacodynamic relationships. Comprehensive and limited pharmacokinetics were obtained at multiple visits in emphysema subjects treated with placebo (n = 30), intermittent dosing (4 days/week) with low-dose ATRA (1 mg/kg/day, n = 21), or high-dose ATRA (2 mg/kg/day, n = 25) or daily administration of 13-cRA (1 mg/kg/day, n = 40). High-dose ATRA produced the highest peak plasma ATRA Cmax. However, at follow-up, plasma ATRA C(max) was significantly decreased from baseline in subjects whose day 1 levels exceeded 100 ng/mL (P < .0001). In contrast, administration of 13-cRA produced lower plasma ATRA C(max) (<100 ng/mL), but the levels were significantly higher at follow-up than those on day 1 (P < .001). Plasma ATRA levels as determined on day 1 correlated with changes in pulmonary diffusing capacity at 6 months, consistent with concentration-dependent biologic effects (r2 = -0.25). The authors conclude that intermittent therapy with high-dose ATRA produced the greatest ATRA exposure, but alternative approaches for limiting self-induced ATRA catabolism should be sought.

The presence of emphysema does not affect the systemic bioactivity of inhaled fluticasone in severe chronic obstructive pulmonary disease.

AIMS: To assess the systemic bioactivity of fluticasone proprionate (FP) 2000 micro g daily on sensitive adrenal and bone markers in severe chronic obstructive pulmonary disease (COPD) patients with or without significant emphysema. METHODS: Ten patients without emphysema (COPD group: age 55 years, FEV(1) 51% predicted and DL(CO) 83% predicted) and 10 patients with emphysema (COPDE group: age 59 years, FEV(1) 43% predicted and DL(CO) 49% predicted) received FP 2000 micro g daily via a spacer for 2 weeks. There was a 1-week washout period prior to FP treatment where patients were given salmeterol and oxitropium, after stopping their usual inhaled corticosteroids for the duration of the study. Measurements including overnight 10 h urinary cortisol excretion corrected for creatinine (OUCC) and serum osteocalcin concentrations were performed at baseline following washout and after 2 weeks of FP. RESULTS: Values for OUCC and serum osteocalcin concentrations pre- and post-FP were not significantly different between the COPD and COPDE groups. There was significant suppression of OUCC (nmol mmol(-1)) by FP treatment within the COPD group (P = 0.03): 7.86 vs 4.64 (95% CI on the difference 0.47, 5.98), and within the COPDE group (P = 0.006): 7.13 vs 4.27 (95% CI on the difference: 1.03, 4.69). Likewise, there was significant suppression of osteocalcin concentration (nmol l(-1)) by FP treatment within the COPD group (P = 0.04): 7.24 vs 6.34 (95% CI on the difference: 0.01, 1.78), and within the COPDE group (P = 0.03): 6.92 vs 5.72 (95% CI on the difference: 0.12, 2.29). CONCLUSIONS: Severe COPD patients who are receiving high dose FP are susceptible to the development of systemic adverse effects, irrespective of the presence of emphysema.

Comparison of three protocols for breathing exercises during immersion in 38 degrees C water for chronic obstructive pulmonary disease.

Respiratory function test, arterial blood gas analysis, and ejection fraction were used to compare three protocols of breathing exercises during immersion in 38 degrees C water. Therapy was given for 2 mo to patients with stable chronic obstructive pulmonary disease. Protocol A consisted of a total exercise period of 20 min/wk (10 min/day, 2 days/wk) and was performed by 7 patients (5 cases of asthma and 2 cases of emphysema). Protocol B consisted of a total exercise period of 120 min/wk (20 min x 2 per day at 10:00 am and 3:00 pm, 3 days/wk) and was performed by 9 patients (6 asthmas and 3 emphysemas). Protocol C consisted of a total exercise period of 120 min/wk (20 min/day, 6 days/wk) and was performed by 8 patients (4 asthmas and 4 emphysemas). The ratio of forced expired volume in one second to forced vital capacity (FEV1.0%) was significantly increased in protocols B and C (P < 0.01). The ratio of forced vital capacity to the predicted normal value (%FVC) was not changed in any of the three protocols. A significant increase in peak flow was observed in protocols B and C (P < 0.05). The maximal expiratory flow at 25% (V25) was not changed in any of the three protocols. PaO2 was significantly increased and PacO2 was significantly decreased in protocol B (P < 0.01 and P < 0.05, respectively), whereas only PaCO2 was significantly decreased in protocol C (P < 0.05). Ejection fraction was increased in protocols B and C. These results suggest that exercise for a total period of 120 min/wk is preferable to that of 20 min/wk in COPD.