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YEAR IN REVIEW
Year in review 2014: Chronic obstructive pulmonary disease, asthma and airway biology TOW KEANG LIM,1 FANNY W.S. KO,2 PAUL S. THOMAS,3,4 CHRIS GRAINGE5,6 AND IAN A. YANG7,8 1
Department of Medicine, National University Hospital, Singapore, and 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China, and 3Inflammation and Infection Research Centre and Prince of Wales’ Hospital Clinical School, Faculty of Medicine, University of New South Wales, Kensington, and 4Department of Respiratory Medicine, Prince of Wales’ Hospital, Randwick, and 5School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, and 6Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, and 7Department of Thoracic Medicine, The Prince Charles Hospital, and 8School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
Key words: airway biology, asthma, chronic obstructive pulmonary disease. Abbreviations: CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; COPD, chronic obstructive pulmonary disease; CT, computed tomography; EBC, exhaled breath condensate; FeNO, exhaled nitric oxide; FEV1, forced expiratory volume in 1 s; FFM, free fat mass; FVC, forced vital capacity; GOR, gastrooesophageal reflux; HMGB1, high-mobility group box 1; hOGG1, human 8-oxoguanine DNA glycosylase; ICAM, intercellular adhesion molecule-1; MDA, malondialdehyde; MIP-2, macrophage inflammatory protein 2; MNA-SF, Mini Nutritional Assessment Short-Form; NEA, non-eosinophilic asthma; NIV, non-invasive ventilation; PBMC, peripheral blood mononuclear cell; QOL, quality of life; rBCG, recombinant bacille Calmette-Guerin; SNP, single nucleotide polymorphism.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE T.K. Lim and Fanny W.S. Ko In 2014, a wide range of Respirology papers looked at the mechanisms behind, assessment of, and treatment and management options for chronic obstructive pulmonary disease (COPD).
Mechanisms COPD is characterized by progressive airflow obstruction, airway inflammation and systemic effects or co-morbidities.1 The disease state of COPD is likely the product of genetic and environmental factors. A previous genome-wide association study has identified some genomic regions that are associated with COPD-related lung function in 20 288 participants of
Correspondence: Ian A. Yang, Department of Thoracic Medicine, The Prince Charles Hospital, Rode Road, Chermside, Brisbane, Qld. 4032, Australia. Email: [email protected] Received 12 January 2015; accepted 14 January 2015. Article first published online: 12 February 2015 © 2015 Asian Pacific Society of Respirology
European ancestry.2 A recent study by Yang et al. assessed these regions in the Chinese Han population and found that the single nucleotide polymorphism (SNP) (rs3995090) in 5-hydroxytryptamine receptor-4 was associated with COPD in never-smokers, and the SNP (rs2070600) in advanced glycation end-products receptor was associated with pulmonary function (forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC) ratio).3 For genetic factors, ADAM33 gene was first identified as a susceptibility gene for asthma. It was subsequently considered as a possible causative gene for COPD because of its association with lung function decline in the general population, children and asthma patients. Zhang et al.4 performed a comprehensive meta-analysis on ADAM33 polymorphisms and COPD risks and observed that ADAM33 S1 polymorphism is a risk factor for COPD among the Chinese and smoking populations, and that Q-1 polymorphism is a risk factor for COPD among the overall populations including Chinese and Caucasians. However, ADAM33 F + 1, S2, T1 or V4 polymorphism showed no significant associations with COPD risks. Genes related to vitamin D metabolism may affect the progression and thus the severity of COPD by modifying susceptibility to exacerbation. A recent study by Ishii et al.5 found that Japanese subjects with SPN with a C allele at rs4588 of the group component, a carrier protein for vitamin D in the plasma that transports vitamin D to various organs, exhibited a higher frequency of exacerbations, greater susceptibility to COPD and a tendency for rapid decline of airflow obstruction. Apart from genes, some proteins are also found to have association with the development of COPD. High-mobility group box 1 (HMGB1) is originally identified as a nuclear DNA-binding protein that is important for gene expression and proper transcriptional regulation. Ko et al.6 found that the levels of HMGB1 in human plasma and expression of HMGB1 in human pulmonary surgical specimens were significantly elevated in smokers with COPD compared with Respirology (2015) 20, 510–518 doi: 10.1111/resp.12488
Year in review 2014
smokers without COPD and healthy controls. In addition, plasma HMGB1 level negatively correlated with FEV1/FVC ratio in smokers, but not in non-smokers. These results suggested that in individuals with smoking risk factor, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD. Oxidative stress is also thought to play a pivotal role in the pathogenesis of COPD. Human 8-oxoguanine DNA glycosylase (hOGG1) serves as a DNA repair enzyme by excising the oxidized guanine base in DNA. Yang et al.7 found a low level of hOGG1 in induction in peripheral blood mononuclear cell (PBMC) in COPD patients. There was also a high level of 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-OHdG), a marker of reactive oxygen species-induced oxidative DNA damage, in PBMC. Antus et al.8 assessed the level of malondialdehyde (MDA), an end-product of polyunsaturated fatty acid peroxidation, in sputum and exhaled breath condensate (EBC) in patients with acute exacerbation of COPD. They found that MDA concentrations in sputum are elevated in stable COPD patients compared with healthy controls; and sputum MDA levels are further increased in acute exacerbation of COPD requiring hospitalization. Measurement of MDA in EBC, on the other hand, did not appear to reflect oxidative stress within the airways. These suggested that PBMC 8-OHdG and hOGG1 and sputum MDA may serve as potential markers of lung damage. Interventions like smoking cessation can modify the risk of development of COPD. Fonseca Wald et al.,9 in their recent review, observed that greater intake of dietary fibre has been consistently associated with reduced COPD risk, better lung function and reduced respiratory symptoms. Results on the associations between fatty acids and COPD however are inconsistent. More research is needed to see if dietary or other interventions can decrease oxidative stress and inflammation in the airway and decrease the risk of COPD.
Assessment Identification of COPD is the first step in its management. A study from Malaysia found that when using a handheld device, the prevalence of COPD, defined as ratio of FEV1/FEV in 6 s
YEAR IN REVIEW
Year in review 2014: Chronic obstructive pulmonary disease, asthma and airway biology TOW KEANG LIM,1 FANNY W.S. KO,2 PAUL S. THOMAS,3,4 CHRIS GRAINGE5,6 AND IAN A. YANG7,8 1
Department of Medicine, National University Hospital, Singapore, and 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China, and 3Inflammation and Infection Research Centre and Prince of Wales’ Hospital Clinical School, Faculty of Medicine, University of New South Wales, Kensington, and 4Department of Respiratory Medicine, Prince of Wales’ Hospital, Randwick, and 5School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, and 6Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, and 7Department of Thoracic Medicine, The Prince Charles Hospital, and 8School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
Key words: airway biology, asthma, chronic obstructive pulmonary disease. Abbreviations: CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; COPD, chronic obstructive pulmonary disease; CT, computed tomography; EBC, exhaled breath condensate; FeNO, exhaled nitric oxide; FEV1, forced expiratory volume in 1 s; FFM, free fat mass; FVC, forced vital capacity; GOR, gastrooesophageal reflux; HMGB1, high-mobility group box 1; hOGG1, human 8-oxoguanine DNA glycosylase; ICAM, intercellular adhesion molecule-1; MDA, malondialdehyde; MIP-2, macrophage inflammatory protein 2; MNA-SF, Mini Nutritional Assessment Short-Form; NEA, non-eosinophilic asthma; NIV, non-invasive ventilation; PBMC, peripheral blood mononuclear cell; QOL, quality of life; rBCG, recombinant bacille Calmette-Guerin; SNP, single nucleotide polymorphism.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE T.K. Lim and Fanny W.S. Ko In 2014, a wide range of Respirology papers looked at the mechanisms behind, assessment of, and treatment and management options for chronic obstructive pulmonary disease (COPD).
Mechanisms COPD is characterized by progressive airflow obstruction, airway inflammation and systemic effects or co-morbidities.1 The disease state of COPD is likely the product of genetic and environmental factors. A previous genome-wide association study has identified some genomic regions that are associated with COPD-related lung function in 20 288 participants of
Correspondence: Ian A. Yang, Department of Thoracic Medicine, The Prince Charles Hospital, Rode Road, Chermside, Brisbane, Qld. 4032, Australia. Email: [email protected] Received 12 January 2015; accepted 14 January 2015. Article first published online: 12 February 2015 © 2015 Asian Pacific Society of Respirology
European ancestry.2 A recent study by Yang et al. assessed these regions in the Chinese Han population and found that the single nucleotide polymorphism (SNP) (rs3995090) in 5-hydroxytryptamine receptor-4 was associated with COPD in never-smokers, and the SNP (rs2070600) in advanced glycation end-products receptor was associated with pulmonary function (forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC) ratio).3 For genetic factors, ADAM33 gene was first identified as a susceptibility gene for asthma. It was subsequently considered as a possible causative gene for COPD because of its association with lung function decline in the general population, children and asthma patients. Zhang et al.4 performed a comprehensive meta-analysis on ADAM33 polymorphisms and COPD risks and observed that ADAM33 S1 polymorphism is a risk factor for COPD among the Chinese and smoking populations, and that Q-1 polymorphism is a risk factor for COPD among the overall populations including Chinese and Caucasians. However, ADAM33 F + 1, S2, T1 or V4 polymorphism showed no significant associations with COPD risks. Genes related to vitamin D metabolism may affect the progression and thus the severity of COPD by modifying susceptibility to exacerbation. A recent study by Ishii et al.5 found that Japanese subjects with SPN with a C allele at rs4588 of the group component, a carrier protein for vitamin D in the plasma that transports vitamin D to various organs, exhibited a higher frequency of exacerbations, greater susceptibility to COPD and a tendency for rapid decline of airflow obstruction. Apart from genes, some proteins are also found to have association with the development of COPD. High-mobility group box 1 (HMGB1) is originally identified as a nuclear DNA-binding protein that is important for gene expression and proper transcriptional regulation. Ko et al.6 found that the levels of HMGB1 in human plasma and expression of HMGB1 in human pulmonary surgical specimens were significantly elevated in smokers with COPD compared with Respirology (2015) 20, 510–518 doi: 10.1111/resp.12488
Year in review 2014
smokers without COPD and healthy controls. In addition, plasma HMGB1 level negatively correlated with FEV1/FVC ratio in smokers, but not in non-smokers. These results suggested that in individuals with smoking risk factor, high expression of HMGB1 in the blood and lungs is related to the lung function impairment and appears to be associated with the development of COPD. Oxidative stress is also thought to play a pivotal role in the pathogenesis of COPD. Human 8-oxoguanine DNA glycosylase (hOGG1) serves as a DNA repair enzyme by excising the oxidized guanine base in DNA. Yang et al.7 found a low level of hOGG1 in induction in peripheral blood mononuclear cell (PBMC) in COPD patients. There was also a high level of 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-OHdG), a marker of reactive oxygen species-induced oxidative DNA damage, in PBMC. Antus et al.8 assessed the level of malondialdehyde (MDA), an end-product of polyunsaturated fatty acid peroxidation, in sputum and exhaled breath condensate (EBC) in patients with acute exacerbation of COPD. They found that MDA concentrations in sputum are elevated in stable COPD patients compared with healthy controls; and sputum MDA levels are further increased in acute exacerbation of COPD requiring hospitalization. Measurement of MDA in EBC, on the other hand, did not appear to reflect oxidative stress within the airways. These suggested that PBMC 8-OHdG and hOGG1 and sputum MDA may serve as potential markers of lung damage. Interventions like smoking cessation can modify the risk of development of COPD. Fonseca Wald et al.,9 in their recent review, observed that greater intake of dietary fibre has been consistently associated with reduced COPD risk, better lung function and reduced respiratory symptoms. Results on the associations between fatty acids and COPD however are inconsistent. More research is needed to see if dietary or other interventions can decrease oxidative stress and inflammation in the airway and decrease the risk of COPD.
Assessment Identification of COPD is the first step in its management. A study from Malaysia found that when using a handheld device, the prevalence of COPD, defined as ratio of FEV1/FEV in 6 s
