Unravelling the Many Faces of COPD to Optimize Its Care and Outcomes
Animal models of COPD: What do they tell us?
Bernadette Jones, Chantal Donovan, Gang Liu, Henry M Gomez, Vrushali Chimankar, Celeste L Harrison, Cornelis H Wiegman, Ian M Adcock, Darryl A Knight, Jeremy A Hirota & Philip M Hansbro
Respiratory Sleep Disorders
Obstructive sleep apnoea pathogenesis from mild to severe: Is it all the same?
The fractional exhaled nitric oxide (FeNO) level at a visit before an asthma exacerbation (AE) was significantly higher in asthmatic patients who experienced an AE within the next 12 months. The optimal cut-off point of FeNO level for the prediction of an AE is 31 ppb.
Comprehensive attenuation of IL-25-induced airway hyperresponsiveness, inflammation and remodelling by the PI3K inhibitor LY294002
Ping Huang, Yan Li, Ze Lv, Jingjing Wang, Qian Zhang, Xiujuan Yao, Chris J Corrigan, Kewu Huang, Wei Wang & Sun Ying
The phosphoinositide 3-kinase (PI3K) pan-inhibitor LY294002 effectively attenuated IL-25-induced airway inflammation, hyperresponsiveness and remodelling in a murine asthma model in an in vivo condition.
Clinically remitted childhood asthma is associated with airflow obstruction in middle-aged adults
We performed a large cross-sectional analysis to evaluate the association of remitted childhood asthma with lung function in middle-aged adults. We found that not only adulthood asthma, but also remitted childhood asthma was associated with airflow obstruction.
Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC
Airway epithelial cells, in particular goblet cells, appear to be an important source of periostin in the serum and sputum of asthmatic patients. IL-13 induced periostin production in NHBE cells and this was mediated by Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) and MEK/extracellular regulated protein kinase (ERK) pathways. Inhibiting periostin attenuated IL-13-driven MUC5AC mucin secretion.
Bronchiectasis in yellow nail syndrome
Georgia Woodfield, Mitzi Nisbet, Joe Jacob, Wing Mok, Michael R Loebinger, David M Hansell, Athol U Wells & Robert Wilson
Bronchiectasis in yellow nail syndrome (YNS) has distinct features which influence clinical presentation and management. Bronchiectasis in YNS is milder than in idiopathic bronchiectasis, with less upper and middle lobe disease, but increased mucus plugging. A better understanding of aetiology may influence future research and management decisions.
Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition
Alejandro A Diaz, Thomas P Young, Diego J Maselli, Carlos H Martinez, Erick S Maclean, Andrew Yen, Chandra Dass, Scott A Simpson, David A Lynch, Gregory L Kinney, John E Hokanson, George R Washko & Raul San José Estépar
In 106 never-smokers adults, the mean ratio of the diameters of the bronchial lumen and adjacent pulmonary artery, a defining radiological feature of bronchiectasis, was 0.79, varied by airway generation and in 8.5% of them was >1. This metric was directly related with expiratory airflow regardless of body size.
Role of BMI, airflow obstruction, St George's Respiratory Questionnaire and age index in prognostication of Asian COPD
Hiang Ping Chan, Amartya Mukhopadhyay, Pauline Lee Poh Chong, Sally Chin, Xue Yun Wong, Venetia Ong, Yiong Huak Chan, Tow Keang Lim & Jason Phua
The BMI, airflow obstruction, St George's Respiratory Questionnaire and age (BOSA) index is a new tool, built and prospectively validated in this study for prognosticating patients with COPD. It predicts mortality moderately well and is at least equivalent to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 in Asian patients. It has the potential to be used widely as complex testing or equipment is not required.
Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia
In patients with COPD without resting hypoxaemia, mean pulmonary artery pressure (mPAP) significantly correlated with oxygen saturation of peripheral artery (SpO2 ) at the end of the 6-min walk test (6MWT). In multivariate analysis, only SpO2 at the end of the 6MWT and 6-min walk distance (6MWD) remained as independent predictors of mPAP. Thus, exercise capacity and exercise hypoxaemia predict pulmonary hypertension (PH) in COPD patients without resting hypoxaemia.
Expression of RANKL by peripheral neutrophils and its association with bone mineral density in COPD
Peripheral blood neutrophils from male patients with COPD had enhanced expression of the osteoclast activation factor RANKL (receptor activator of NF-kB ligand), which correlated with bone mineral density and lung function of the patients.
Transforming growth factor (TGF) β1 and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis
Malik Q Mahmood, David Reid, Chris Ward, Hans K Muller, Darryl A Knight, Sukhwinder S Sohal & Eugene H Walters
COPD is fundamentally due to small airway fibrosis mainly in smokers. Pathologically, it is associated with active epithelial mesenchymal transition (EMT). Relatively, little has been studied regarding the transforming growth factor (TGF)-β1-pSmad pathway in smokers and COPD. This study facilitates the understanding of EMT-associated pathogenesis of COPD in terms of this pathway.
Relationship between pulmonary hyperinflation and dyspnoea severity during acute exacerbations of cystic fibrosis
Trevor T Nicholson, Peter J Barry, Deirdre F Waterhouse, Geraldine M Nolan, Edward F McKone & Charles G Gallagher
This study explores the relationship between dyspnoea and pulmonary function during acute exacerbations of cystic fibrosis (CF). Indicators of pulmonary hyperinflation, rather than forced expiratory volume in 1s (FEV1), are associated with the severity of dyspnoea during treatment. As total lung capacity (TLC) does not change with treatment, inspiratory capacity (IC) measurement may provide a useful means of assessing treatment response.
Environmental & Occupational Lung Disease
Ecological study on solid fuel use and pneumonia in young children: A worldwide association
Solid fuels and associated biomass pollution have been implicated in an expanded array of adverse health effects. We performed a worldwide ecological assessment and identified that in addition to poverty and other economic indicators, solid fuels independently contribute to the prevalence of acute pneumonia in young children.
Pulmonary Vascular Disease
Bromodomain and extra-terminal protein mimic JQ1 decreases inflammation in human vascular endothelial cells: Implications for pulmonary arterial hypertension
Sharon Mumby, Natalia Gambaryan, Chao Meng, Frederic Perros, Marc Humbert, S John Wort & Ian M Adcock
Endothelial cell inflammation and proliferation are important in the pathogenesis of pulmonary arterial hypertension (PAH). Bromodomain and extra-terminal (BET) mimics reduced inflammation and cell proliferation in primary human pulmonary vascular endothelial cells. The enhanced histone acetyltransferase (HAT) activity in PAH suggests that BET mimics may be effective in PAH although experiments in disease cells/tissues are required.
Gas exchange responses during 6-min walk test in patients with pulmonary arterial hypertension
Norman R Morris, Helen Seale, Julie Harris, Kathleen Hall, Aaron C W Lin & Fiona Kermeen
Pulmonary arterial hypertension (PAH) patients have reduced exercise tolerance and characteristic gas exchange responses. Inclusion of gas exchange measurements during the 6-min walk test showed that individuals with more severe disease and more advance pharmacotherapy had poorer gas exchange during exercise.
Prognostic value of right ventricular ejection/filling parameters in IPAH using cardiac magnetic resonance: A prospective pilot study
Wen Li, Tao Yang, Yan Zhang, Qing Gu, Zhi-Hong Liu, Xin-Hai Ni, Qin Luo, Chang-Ming Xiong & Jian-Guo He
The prognostic values of cardiovascular magnetic resonance (CMR)-derived right ventricular (RV) ejection/filling parameters in idiopathic pulmonary arterial hypertension (IPAH) patients were examined. RV time to peak ejection rate (TPER) and TPER/time of a cardiac cycle (TCC) were found to reflect RV early systolic function, and thus may be prognostic predictive values for long-term cardiac impairment in IPAH patients.
Prognostic and pathophysiological marker for patients with chronic thromboembolic pulmonary hypertension: Usefulness of diffusing capacity for carbon monoxide at diagnosis
This is the first study identifying decreased diffusing capacity for carbon monoxide (DLCO)/alveolar ventilation (VA) (<80%) as an independent poor prognostic factor in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. This study also demonstrated that DLCO/VA may reflect peripheral microvasculopathy, which is a major cause of poor outcome.
Paediatric Lung Disease
Risk factors for morbidities and mortality in children following pneumonectomy
Risk factors related to morbidity and mortality after pneumonectomy (PNE) have been described in adults. This study explores the risk factors following PNE in children. Age ≤3 years and the need for ventilation assistance for 4 days or longer was associated with increased risk of morbidity and mortality.
Malignant pleural fluid from mesothelioma has potent biological activities
Hui Min Cheah, Sally M Lansley, Julius F Varano della Vergiliana, Ai Ling Tan, Rajesh Thomas, Su Lyn Leong, Jenette Creaney & Yun Chor Gary Lee
Malignant pleural effusion (MPE) is often viewed as a by-product of cancer with breathlessness as the only significant consequence. Its production and role in cancer biology are unclear. This study provides 'proof-of-concept' evidence revealing potent biological capabilities in cancer progression. Further understanding of MPE may uncover exciting therapeutic possibilities.
Target oxygen saturation range: 92–96% Versus 94–98%
Richard Beasley, Jimmy Chien, James Douglas, Leonie Eastlake, Claude Farah, Gregory King, Rosemary Moore, Janine Pilcher, Michael Richards, Sheree Smith & Haydn Walters