No abstract

PurposeThe GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations. The GOLD 2017 proposes a new classification whereby patients are grouped as A–D according to their symptoms and history of exacerbations. However, the clinical characteristics and outcomes in these patients are not well documented.Patients and methodsIn this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. All patients with stable COPD were classified into the four groups defined by GOLD 2017. The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.ResultsFour hundred and one patients with stable COPD were identified. There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D. Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A. Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period. Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B). Mortality was not different between the high-risk and low-risk groups.ConclusionThe results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality.

We propose a method to improve the enhanced permeability and retention (EPR) effect of nanomedicines based on tumor-specific vasodilation using a nitric oxide (NO) donor-containing liposome. NONOate, a typical NO donor, was incorporated into a PEGylated liposome to retard the protonation-induced release of NO from NONOate by the protecting lipid bilayer membrane. The NONOate-containing liposome (NONOate-LP) showed similar blood retention to an empty PEGylated liposome but almost twice the amount accumulated within the tumor. This improvement in the EPR effect is thought to have been caused by specific vasodilation in the tumor tissue by NO released from the NONOate-LP accumulated in the tumor. The improved EPR effect by NONOate-LP will be useful for the accumulation of co-administered nanomedicines.

Smoking-related interstitial lung abnormalities are different from specific forms of fibrosing lung disease which might be associated with poor prognoses. Chronic obstructive pulmonary disease with comorbid interstitial lung abnormalities and that with pulmonary fibrosis are considered different diseases; however, they could share a common spectrum. We aimed to evaluate the clinical characteristics of Japanese patients with chronic obstructive pulmonary disease and comorbid interstitial lung abnormalities. In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. We evaluated the clinical characteristics of patients with chronic obstructive pulmonary disease with and without comorbid interstitial lung abnormalities by comparing the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period. Among 463 patients with chronic obstructive pulmonary disease, 30 (6.5%) developed new interstitial lung abnormalities during the observational period. After 1-to-3 propensity score matching, we found that the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period was 0.06 and 0.23 per year in the interstitial lung abnormality and control groups, respectively (P = 0.043). Our findings indicate slow progression of interstitial lung abnormality lesions in patients with pre-existing chronic obstructive pulmonary disease. Further, interstitial lung abnormality development did not significantly influence on chronic obstructive pulmonary disease exacerbation. We speculate that post-chronic obstructive pulmonary disease interstitial lung abnormalities might involve smoking-related interstitial fibrosis, which is different from specific forms of fibrosing lung disease associated with poor prognoses.

Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m ( 99m Tc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases. Baseline 99mTc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n5168) and IPF (n597) against mortality and disease progression.In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01-1.03; p50.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25-3.53; p50.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00-1.02; p,0.01).Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease.