Disproportionally Impaired Diffusion Capacity Relative to Airflow Limitation in COPD

Forced expiratory volume in 1 s (FEV₁) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (D_LCO). This study tested whether a disproportionally impaired D_LCO relative to FEV₁ (FEV₁ z-score>-3 and D_LCO z-score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose D_LCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired D_LCO relative to FEV₁ was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired D_LCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV₁ z-score>-3 and D_LCO z-score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired D_LCO group than in the reference group (hazard ratio [95% confidence interval] = 3.09 [1.52–6.29]) and similar to the D_LCO z-score≤-3 and FEV₁ z-score≤-3 group. The disproportionally impaired D_LCO relative to FEV₁ is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD

Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity

Fractional exhaled nitric oxide measurements in rhinitis and asthma in children.

Exaled nitric oxide (FeNO) is considered a good noninvasive marker to assess airway inflammation in asthma and allergic rhinitis. In asthma, exhaled NO is very useful to verify adherence to therapy, and to predict upcoming asthma exacerbations. It has been also proposed that adjusting anti-inflammatory drugs guided by the monitoring of exhaled NO, could improve overall asthma control. Other studies showed increased FeNO levels in subjects with allergic rhinitis

Synchrotron x-ray imaging of pulmonary alveoli in respiration in live intact mice

Despite nearly a half century of studies, it has not been fully understood how pulmonary alveoli, the elementary gas exchange units in mammalian lungs, inflate and deflate during respiration. Understanding alveolar dynamics is crucial for treating patients with pulmonary diseases. In-vivo, real-time visualization of the alveoli during respiration has been hampered by active lung movement. Previous studies have been therefore limited to alveoli at lung apices or subpleural alveoli under open thorax conditions. Here we report direct and real-time visualization of alveoli of live intact mice during respiration using tracking X-ray microscopy. Our studies, for the first time, determine the alveolar size of normal mice in respiration without positive end expiratory pressure as 58 ± 14 (mean ± s.d.) μm on average, accurately measured in the lung bases as well as the apices. Individual alveoli of normal lungs clearly show heterogeneous inflation from zero to ~25% (6.7 ± 4.7% (mean ± s.d.)) in size. The degree of inflation is higher in the lung bases (8.7 ± 4.3% (mean ± s.d.)) than in the apices (5.7 ± 3.2% (mean ± s.d.)). The fraction of the total tidal volume allocated for alveolar inflation is 34 ± 3.8% (mean ± s.e.m). This study contributes to the better understanding of alveolar dynamics and helps to develop potential treatment options for pulmonary diseases

Adequacy of therapy for people with both COPD and heart failure in the UK : historical cohort study

Acknowledgments We thank Derek Skinner for his contributions to the data acquisition and handling and Carole Nicholls and Priyanka Raju Konduru for statistical support. Writing and editorial support was provided by Elizabeth V. Hillyer, DVM, supported by Novartis Pharma AG, Basel, Switzerland. Funding This work was supported by Novartis. Employees of the sponsor (listed as authors) participated in the study design, interpretation of the results, writing of the report, and the decision to submit the paper for publication.Peer reviewedPublisher PD

Blood Eosinophil Count Predicts Treatment Failure and Hospital Readmission for COPD

ACKNOWLEDGEMENTS This study was funded by AstraZeneca. Editorial support was provided by Joanne M. Faysal, MS, and Jennie G. Jacobson, PhD, CMPP, of JK Associates, Inc., and Michael A. Nissen, ELS, of AstraZeneca. This support was funded by AstraZeneca. DATA-SHARING STATEMENT Data underlying the findings described in this manuscript may be requested in accordance with AstraZeneca’s data-sharing policy described at https://astrazenecagroupdt.pharmacm.com/DT/HomePeer reviewedPublisher PD

Does Changing Inhaler Device Impact Real-Life Asthma Outcomes? : Clinical and Economic Evaluation

This study was funded by Mundipharma Korea Limited (Seoul, Korea).Peer reviewedPostprin

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD : results from a national database

Acknowledgments The authors would like to thank Kyungjoo Kim for the confident statistical analyses in this work. This study was supported by a grant (2014P3300300) from the Korea Centers for Disease Control and Prevention. The abstract of this paper was presented at the Asian Pacific Society of Respirology 20th Congress as an oral presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Respirology.Peer reviewedPublisher PD

Influence of neutropenia on mortality of critically ill cancer patients : results of a meta-analysis on individual data

Background: The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). Methods: Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. Results: Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n = 1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P = 0.90). Conclusion: Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients