Proteomics in asthma and COPD phenotypes and endotypes for biomarker discovery and improved understanding of disease entities

The application of proteomics to respiratory diseases, such as asthma and COPD, has been limited compared to other fields, like cancer. Both asthma and COPD are recognised to be multi-factorial and complex diseases, both consisting of clusters of multiple disease phenotypes. The complexity of these diseases combined with the inaccessibility and invasiveness of disease relevant samples have provided a hurdle to the progress of respiratory proteomics. Advances in proteomic instrumentation and methodology have led to the possibility to identify proteomes in much smaller quantities of biological material. This review focuses on the efforts in respiratory proteomics in relation to asthma and COPD, and the importance of identifying subgroups of disease entities to establish appropriate biomarkers, and to enhance the understanding of underlying mechanisms in each subgroup. Careful phenotype characterisation of patient subpopulations is required to make improvement in the field of heterogeneous diseases such as asthma and COPD, and the clusters of phenotypes are likely to encompass subgroups of disease with distinct molecular mechanisms; endotypes. The utilisation of modern advanced proteomics in endotypes of asthma and COPD will likely contribute to the increased understanding of disease mechanisms, establishment of biomarkers for these endotypes and improved patient care.     

Epigenetics in asthma and COPD

Epigenetic mechanisms are likely to play a role in many complex diseases, the extent of which we only beginning to understand. COPD and asthma are two respiratory diseases subject to strong environmental influences depending on underlying genetic susceptibility. Epigenetic mechanisms such as DNA methylation, histone modification and microRNA may be involved in these processes by modulating environmental effects to influence disease development. Given their demonstrated modifiable nature, epigenetic mechanisms may open new possibilities for therapeutic intervention. Here we give an overview of recent developments in the field of respiratory epigenetics in relation to asthma and COPD in the context of our current understanding of mechanisms leading to such diseases.     

ACOS与同期哮喘和COPD患者住院情况调查分析

目的:分析ACOS与同期哮喘和COPD患者住院情况。方法:采取回顾性方法,收集6年内住院ACOS与同期哮喘和COPD患者年龄、性别、所患疾病种类和住院费用等临床资料,分别进行统计和分类汇总。结果:2009-2014年共有1327哮喘患者住院治疗,其中合并COPD有128人,即ACOS占哮喘患者的9.6%。同期收治的慢性支气管炎1989人、肺气肿1634人,但行肺功能检查确诊COPD的仅367人,其中合并哮喘同样为128人,即ACOS占COPD患者的34.9%。性别方面,ACOS组男性最多,仅与哮喘组比较,P0.05;年龄,ACOS介于哮喘和COPD之间;入住ICU、机械通气治疗,ACOS组最少,仅与COPD组比较,P0.05;人均花费最低,与哮喘和COPD组比较,P0.05;死亡情况ACOS组仅有1人死亡,死亡率3组中最低,但P0.05;共存病情况ACOS在合并II型呼吸衰竭和过敏性鼻炎方面,与哮喘相似;在合并肺炎和支气管扩张方面与COPD相似;在合并I型呼吸衰竭、冠心病、糖尿病和肝、肾功能异常方面,三组比较,组间差异无显著统计学意义,P0.05;只有合并高血压,ACOS组明显低于哮喘和COPD组,而且组间差异有显著统计学意义,P0.05。结论:与哮喘和COPD相比,ACOS有其独特的特点。     

The clinical features of the overlap between COPD and asthma

Background

The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.

Methods

We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.

Results

119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.

Conclusion

Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00608764","term_id":"NCT00608764"}}NCT00608764     

Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study

Sleep deprivation is extremely common in the intensive care unit (ICU), and this lack of sleep is associated with low melatonin secretion. The objective of the current study was to explore the effect of exogenous melatonin administration on sleep quality in patients hospitalized in the pulmonary intensive care unit (ICU). We performed a double-blind, placebo-controlled study in the pulmonary ICU of a tertiary care hospital. Eight adult patients hospitalized in the pulmonary ICU with respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD) or with pneumonia were studied. Patients received either 3 mg of controlled-release melatonin or a placebo at 22:00, and sleep quality was evaluated by wrist actigraphy. Treatment with controlled-release melatonin dramatically improved both the duration and quality of sleep in this group of patients. Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the “biologic clock.” This treatment may also help in the prevention of the “ICU syndrome” and accelerate the healing process. (Chronobiology International, 17(1), 71-76, 2000)     

Impact of clinical pathway on clinical outcomes in the management of COPD exacerbation

ABSTRACT: BACKGROUND: Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis. Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care. In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation. METHODS: We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to UniversitiKebangsaan Malaysia Medical Centre (UKMMC). Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group. Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009. Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates. RESULTS: Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group. Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641). For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p < 0.001) and 24.1% less complications (14.7% versus 38.8%, p < 0.001). We did not find any significant differences in readmission and mortality rates. CONCLUSION: The implementation of CP -reduced the length of stay and complication rates of patients hospitalized for acute exacerbation of COPD.     

Effects of Adaptive Support Ventilation and Synchronized Intermittent Mandatory Ventilation on Peripheral Circulation and Blood Gas Markers of COPD Patients with Respiratory Failure

The objective of the study was to investigate the effects of adaptive support ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on peripheral circulation of chronic obstructive pulmonary disease (COPD) patients with respiratory failure. 86 COPD patients with respiratory failure were recruited in this study. Self-control method was used to compare the effect of ASV and SIMV on the parameters of ventilation machine, heart rate, blood pressure, central venous pressure (CVP), and blood gas markers. When the patients in ASV and SIMV groups were compared, respiratory rate, tidal volume, and peak airway pressure (PIP) showed significant difference. When minute ventilation (MV) was compared, no significant difference was shown. When peripheral circulation parameters were compared, peripheral circulation heart rate, SBP, DBP, and CVP showed significant difference. Compared with SIMV group, PaO₂, pH, and SaO₂ values were remarkably increased (P < 0.01) while no significant difference was found for partial pressure of carbon dioxide (pCO₂) when two groups were compared. In conclusion, when mechanical ventilation was used in COPD patients with respiratory failure, ASV can significantly improve clinical outcomes.     

Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO)

Background

It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations. The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.

Methods

914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV₁>50% predicted, and <2 exacerbations/year were recruited. Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients). FEV₁, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.

Results

816 patients (89.3%) concluded the study. FEV₁, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6. We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.

Conclusions

We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators.     

Relevance of human metapneumovirus in exacerbations of COPD

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10⁵ viral copies/ml in nasal lavage and 1.88 × 10⁵ viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.     

Body composition in severe refractory asthma: comparison with COPD patients and healthy smokers

Background

Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated.

Methodology and Principal Findings

213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3–18.3)–19.5(18.4–21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I–III COPD and comparable to those of stage IV COPD patients [18.0(17.3–18.3)–18.8(17.8–20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used.

Conclusions and Significance

SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.     

Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls,asthma and COPD patients

Background

Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying the acidity (pH) of airway secretions in patients with inflammatory lung diseases.

Aim

To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls.

Methods

EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min.

Results

In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05).

Conclusion

We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold.     

Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

Background

Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients.

Methods

Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines.

Results

229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85).

Conclusions

Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients.     

Using information from asthma patients: a trial of information feedback in primary care.

OBJECTIVE--To test the effects of feedback of information about patients'' asthma to primary care teams. DESIGN--Patients'' reports of morbidity, use of health services, and drug use on questionnaire was given to primary care teams. Randomised controlled trial with general practices as the subject of the intervention was used to test effectiveness of supplying information. SETTING--Primary care in district health authority, London. SUBJECTS--23 general practices, each of which notified at least 20 asthmatic patients aged 15-60 years for each principal. Practices were randomly allocated to an invention group (receiving feedback of information on control of asthma) or a control group (no feedback). INTERVENTION--Information on cards inserted in patients'' medical records; booklet copies of information for team members; formal presentation to primary care teams; poster displays of data on patients in each practice. MAIN OUTCOME MEASURES--Type and frequency of asthma symptoms, use of health services, use of asthma drugs. RESULTS--Reported morbidity at entry to the study was substantial: 45% (818) patients reported breathlessness at least once a week. Less than half these patients were using inhaled steroids regularly. Intervention and control groups did not differ in practice or patient characteristics on entry to the study. In spite of the potential for improvement no differences were observed between the two practice groups at the end of the study--for example, breathlessness at least once a week in last six months was experienced by 36% in intervention group v 35% in control group (t = -0.27, P < 0.79); surgery attendance in last six months by 48% v 48% (t = -0.05, P < 0.96); regular use of inhaled steroids by 60% v 58% (t = 0.51, P < 0.62). CONCLUSION--Feedback to general practitioners of information about patients'' asthma does not on its own lead to change in the outcome of clinical care.     

Soy consumption and risk of COPD and respiratory symptoms: a case-control study in Japan

Background

To investigate the relationship between soy consumption, COPD risk and the prevalence of respiratory symptoms, a case-control study was conducted in Japan.

Methods

A total of 278 eligible patients (244 men and 34 women), aged 50–75 years with COPD diagnosed within the past four years, were referred by respiratory physicians, while 340 controls (272 men and 68 women) were recruited from the community. All participants underwent spirometric measurements of respiratory function. Information on demographics, lifestyle characteristics and habitual food consumption was obtained using a structured questionnaire.

Results

Total soy consumption was positively correlated with observed lung function measures. The mean soy intake was significantly higher among controls (59.98, SD 50.23 g/day) than cases (44.84, SD 28.5 g/day). A significant reduction in COPD risk was evident for highest versus lowest quartile of daily intake of total soybean products, with adjusted odds ratio (OR) 0.392, 95% CI 0.194–0.793, p for trend 0.001. Similar decreases in COPD risk were associated with frequent and higher intake of soy foods such as tofu and bean sprouts, whereas respiratory symptoms were inversely associated with high consumption of soy foods, especially for breathlessness (OR 0.989, 95% CI 0.982–0.996).

Conclusion

Increasing soy consumption was associated with a decreased risk of COPD and breathlessness.     

Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer,COPD, and asthma

Introduction: Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges.

Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma.

Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.     

The metabolomics of airway diseases,including COPD,asthma and cystic fibrosis

Abstract

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are characterized by airway obstruction and an inflammatory process. Reaching early diagnosis and discrimination of subtypes of these respiratory diseases are quite a challenging task than other chronic illnesses. Metabolomics is the study of metabolic pathways and the measurement of unique biochemical molecules generated in a living system. In the last decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. In this article, we review the current state of the metabolomics of COPD, asthma and CF with a focus on the different methods and instrumentation being used for the discovery of biomarkers in research and translation into clinic as diagnostic aids for the choice of patient-specific therapies.     

Lymphocytes apoptosis in patients with acute exacerbation of asthma

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum. Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anti-cytokine antibodies. Anti-TNF-alpha antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-alpha acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.     

Qualitative study of views of health professionals and patients on guided self management plans for asthma

ObjectivesTo explore the views held by general practitioners, practice nurses, and patients about the role of guided self management plans in asthma care.DesignQualitative study using nine focus groups that each met on two occasions.SettingSouth Wales.Subjects13 asthma nurses, 11 general practitioners (six with an interest in asthma), and 32 patients (13 adults compliant with treatment, 12 non-compliant adults, and seven teenagers).ResultsNeither health professionals nor patients were enthusiastic about guided self management plans, and, although for different reasons, almost all participants were ambivalent about their usefulness or relevance. Most professionals opposed their use. Few patients reported sustained use, and most felt that plans were largely irrelevant to them. The attitudes associated with these views reflect the gulf between the professionals'' concept of the “responsible asthma patient” and the patients'' view.ConclusionsAttempts to introduce self guided management plans in primary care are unlikely to be successful. A more patient centred, patient negotiated plan is needed for asthma care in the community.     

Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study

Background

Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.

Methods

114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV₁ 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue⁺) area (%), proliferating (Ki-67⁺) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.

Results

Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).

Conclusion

Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).

Trial registration

NCT00158847     

Bone Metabolism Status and Associated Risk Factors in Elderly Patients with Chronic Obstructive Pulmonary Disease (COPD)

The prevalence of osteoporosis in older patients with chronic obstructive pulmonary disease (COPD) is higher than in the age-matched elderly patients, but the exact cause in relation to COPD is not clear. We hypothesized that the underlying causes for this difference are related to bone metabolism with the possible risk factors that include the duration of COPD, GOLD grade, cor pulmonale, the frequencies of acute exacerbations within the past year, smoking and inhaled corticosteroid therapy. We conducted a matched-pair study of 100 patients aged older than 65 years at the Southwest Hospital from May to November 2012. The enrolled patients with COPD were matched to controls for age and gender. Clinical characteristics of cohorts were recorded. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and osteoporosis was diagnosed according to the definition of WHO. All cohorts accepted bone metabolism marker measurement, including Procollagen type 1 aminoterminal propeptide (P1NP), β-C-telopeptides of type I collagen (βCTX), and N-terminal midmolecule fragment osteocalcin (N-MID OC). Statistical analysis was calculated using the student’s t test, ANOVA and multiple regression analysis at a significance level set at a p < 0.05. Circulating biochemical markers of bone formation (P1NP), resorption (βCTX) and turnover (N-MID OC) were significantly lower in the COPD group than control group, while mean 25-OH Vitamin D was similar in two groups. The P1NP, βCTX, and N-MID OC were still lower in men with COPD, but only P1NP was lower in women with COPD compared to that of controls. Multiple regression analysis in COPD group suggests that age, the frequency of acute exacerbation, and BMD are independent risk factors for P1NP. The frequency of acute exacerbation within the past one year and 25-OH D level are independent risk factors for βCTX; the frequency of acute exacerbation is the only independent risk factor for N-MID OC. These were significant differences in bone metabolism in patients with or without COPD. These results should help us to further understand the cause of osteoporosis and fractures and conduce to prevent osteoporosis in patients with COPD.