[Show abstract][Hide abstract] ABSTRACT: In patients with COPD, CT assessment of emphysema and airway disease is known to be associated with lung function and 6-minute walk distance. However, it remains to be determined whether low attenuation area (LAA) on CT is associated with aerobic capacity assessed using cardiopulmonary exercise testing (CPET). In this prospective observational study, we repeatedly conducted high-resolution CT and CPET using a treadmill in 81 COPD patients over a median interval of 3.5 years. Two investigators independently scored LAA on images obtained at the aortic arch level, tracheal bifurcation level, and supradiaphrag-matic level. Grades for the images of each lung were added to yield the total LAA score. Total LAA score was negatively correlated with peak aerobic capacity (V _ O 2) (p<0.001, r =-0.485). LAA scores of the upper (aortic arch level) and the lower (supradiaphragmatic level) lungs were both significantly associated with peak V _ O 2. There was a significant correlation between total LAA score and peak CO 2 output (V _ CO 2) (p<0.001, r =-0.433). Total LAA score was correlated with oxygen saturation at peak exercise (p<0.001, r =-0.634) and the estimated dead space fraction (p<0.001, r = 0.416). The mean annual change in total LAA score was significantly correlated with those in peak V _ O 2 (p<0.001, r =-0.546) and peak V _ CO 2 (p<0.001, r =-0.488). The extent of emphysema measured by CT was associated with the results of CPET. The time-dependent changes in CPET data were also correlated with that in total LAA score. CT assessment could be a non-invasive tool to predict aerobic capacity in patients with COPD.
PLoS ONE 04/2015; 10(4). DOI:10.1371/journal.pone.0125053 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymerase chain reaction (PCR) technique is being increasingly used for the microbiological diagnosis of Pneumocystis pneumonia (PCP). As PCR is highly sensitive, it can be positive even in a patient with Pneumocystis colonization. In this study, we evaluated whether the β-d-glucan assay could be used to differentiate between PCP and Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. We retrospectively evaluated data from 166 consecutive patients who underwent bronchoalveolar lavage for the diagnosis of PCP. Serum levels of β-d-glucan in the negative, colonization, probable PCP, and definite PCP groups were 20.2 ± 6.3, 48.8 ± 15.9, 89.9 ± 20.2, 224.9 ± 25.9 pg/mL, respectively. The β-d-glucan levels in the definite PCP group were significantly higher than those in the other 3 groups (p < 0.001). Serum β-d-glucan levels in patients with either definite or probable PCP (173.1 ± 18.8 pg/mL) were significantly greater than those in patients with colonization who had positive PCR results but improved without anti-PCP treatment (p < 0.002). The cut-off level for discrimination was estimated to be 33.5 pg/mL, with which the positive predictive value was 0.925. These results indicate that β-d-glucan is a useful marker to differentiate between PCP and Pneumocystis colonization. A positive β-d-glucan assay result might be a good indication to begin anti-PCP treatment.
Journal of Infection and Chemotherapy 11/2014; 20(11). DOI:10.1016/j.jiac.2014.07.001 · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper lobe emphysema together with lower lobe fibrosis. The aim of this study was to examine whether cytokine levels in the alveolar space are associated with emphysematous changes superimposed on pulmonary fibrosis.
Consecutive patients (n = 102), diagnosed with pulmonary fibrosis were retrospectively evaluated. Cytokine levels and differential cell counts in bronchoalveolar lavage (BAL) fluid, pulmonary function, computed tomography (CT) scores and levels of serum markers were compared between patients with or without emphysema.
Among the 102 patients (14 females, mean age 68 years), 38 (37%) had evidence of upper lobe emphysema on computed tomography (CT). Levels of epithelial neutrophil activating peptide 78 (ENA-78/CXCL5) and interleukin (IL)-8/CXCL8 in BAL fluid were significantly higher in patients with emphysema. Vital capacity (VC, % predicted) was greater, and ratio of forced expiratory volume in 1 s/forced vital capacity and diffusing capacity of carbon monoxide (DL(CO))/alveolar volume (V(A)) were lower in patients with emphysema. CXCL8 and CXCL5 levels were associated with percentage or absolute numbers of neutrophils in BAL fluid. In addition, CXCL8 levels were inversely correlated with VC and DL(CO)/V(A), and positively correlated with composite physiological index (CPI) and the extent of areas of low attenuation on CT.
Increased CXC chemokine levels in the airspaces may be associated with emphysematous lung changes in patients with pulmonary fibrosis.
[Show abstract][Hide abstract] ABSTRACT: Patients with Mycobacterium avium-intracellulare complex (MAC) pulmonary disease often suffer from weight loss. Adipokines are factors secreted by adipocytes, including leptin and adiponectin, as well as some inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). Body mass index (BMI) is known to be inversely correlated with adiponectin and positively with leptin, TNF-alpha, and IL-6.
We aimed to evaluate the levels of serum adipokines, including adiponectin, leptin, TNF-alpha, and IL-6 in patients with MAC pulmonary disease.
Forty consecutive patients with MAC pulmonary disease (8 males; median age 62 years; median BMI 18.1) were examined. Serum levels of adiponectin, leptin, TNF-alpha, and IL-6 were measured with ELISA. Age-, sex- and BMI-matched healthy subjects served as controls.
Serum adiponectin was significantly elevated in patients with MAC pulmonary disease compared with the controls (p < 0.01). In both the patients and controls, serum adiponectin levels were inversely correlated with BMI (p < 0.05). No significant correlation was observed between serum adiponectin levels and C-reactive protein or lung function. Serum leptin levels, which were positively correlated with BMI, did not differ between patients and controls. Serum levels of TNF-alpha and IL-6 were significantly greater in patients with MAC pulmonary disease than in controls. The levels of TNF-alpha and IL-6 were not correlated with BMI and other adipokines examined.
The results of the present study indicate that, in patients with MAC pulmonary disease, adiponectin is inappropriately secreted and may play a role in the pathophysiology of the disease.
[Show abstract][Hide abstract] ABSTRACT: CC chemokines play important roles in the pathogenesis of interstitial lung diseases. Elevated CC chemokine levels have been observed in bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis (IPF).
We aimed to examine whether the levels of four CC chemokines, i.e. monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1 alpha (MIP-1 alpha/CCL3), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22), in BAL fluid are predictive of the prognosis of IPF patients.
We compared the chemokine levels of patients alive 5 years after diagnosis and those who had died. Lung function data, CT scores, and serum markers were also compared.
Among 39 patients (29 males, median age, 60 years), 19 patients (48%) died within 5 years after the diagnosis. Whereas percent vital capacity was not different, percent lung diffusion capacity for carbon monoxide was significantly higher in the surviving patients than in the nonsurviving patients (p < 0.01). Median CCL2 levels of surviving and nonsurviving patients were 154.3 (interquartile range, IQR: 67.3-381.8) and 427.2 (IQR: 329.2-1184.1) pg/ml, respectively (p < 0.02). CCL3 levels in BAL fluid did not differ between the surviving and nonsurviving patients. CCL17 was detected in BAL fluid of 7 patients, 6 of whom died within 5 years. CCL22 was detectable in BAL fluid of 10 patients, only 1 of whom survived. Serum levels of KL-6 and lactate dehydrogenase did not differ between the surviving and nonsurviving patients.
Elevated levels of CCL2, CCL17 and CCL22 in BAL fluid might be predictive of a poor outcome in patients with IPF.
[Show abstract][Hide abstract] ABSTRACT: We studied the effects of TNF-converting enzyme inhibition with Y-41654, which down-regulates the production of soluble TNF-alpha (sTNF-alpha), on acute lung injury induced by intratracheal administration of LPS. We first verified in vitro that pretreatment of isolated alveolar macrophages from Sprague-Dawley male rats with 20 microL of 0.1-mM Y-41654, decreased significantly (P < 0.05) the concentration of sTNF-alpha in cell supernatants induced by 10 microg/mL of LPS. We then studied four groups of rats (each n = 10) including 1) a control group, 2) an LPS group (300 microg /kg, instilled intratracheally), 3) a Y-41654 group, and 4) a treatment group treated with Y-41654 after LPS instillation. Y-41654, 10 mg/kg in 0.7 mL of phosphate-buffered saline, was administered (i.v.), 15 min before and 0.5, 1.5, 2.5, and 3.5 h after saline or LPS instillation. The animals were observed for 4 h. In the animals treated with Y-41654, the concentrations of sTNF-alpha and protein in bronchoalveolar lavage fluid, and the number of neutrophils in lung tissue and bronchoalveolar lavage fluid were significantly lower at 4 h than in the LPS group (P < 0.05). In conclusion, sTNF-alpha plays an important role in the development of acute lung injury induced by intratracheal administration of LPS, in part modulating neutrophil kinetics.