Metabolomics in chronic lung diseases

Chronic lung diseases represent a significant global burden. Their increasing incidence and complexity render a comprehensive, multidisciplinary and personalized approach to each patient, critically important. Most recently, unique biochemical pathways and disease markers have been identified through large‐scale metabolomic studies. Metabolomics is the study of metabolic pathways and the measurement of unique biomolecules in a living system. Analysing samples from different compartments such as bronchoalveolar lavage fluid (BALF) and plasma has proven useful for the characterization of a number of pathological conditions and offers promise as a clinical tool. For example, several studies using mass spectrometry (MS) have shown alterations in the sphingolipid metabolism of chronic obstructive pulmonary disease (COPD) sufferers. In this article, we present a practical review of the application of metabolomics to the study of chronic lung diseases (CLD): COPD, idiopathic pulmonary fibrosis (IPF) and asthma. The insights, which the analytical strategies employed in metabolomics, have provided to the dissection of the biochemistry of CLD and future clinical biomarkers are explored.     

Prevention and control of influenza in persons with chronic obstructive pulmonary disease

Despite recommendations for annual vaccination against influenza, more than half of patients with chronic obstructive pulmonary disease (COPD) in developed countries do not receive this vaccine. Influenza is characterized by its potentially of causing epidemics and by excess morbidity and mortality in patients with COPD and other chronic medical conditions. Good evidence of the efficacy, effectiveness, and cost-effectiveness of influenza vaccination underlines the recommendation of use in patients with COPD. Influenza vaccination could reduce influenza-related complications and exacerbations in patients with COPD, therefore reducing hospitalizations and deaths. Each year, all persons with COPD should be vaccinated with the inactivated trivalent influenza vaccine containing the most frequent two influenza A viral strains and one influenza B viral strain detected in the influenza season of the previous year. To achieve a 100% vaccination rate in patients with COPD, all patients with COPD registered in health insurance companies and attended in health centers and specialized clinics should be vaccinated during the immunization period (October–December). Antiviral therapies could be used as an adjunct to vaccination and to reduce influenza transmission in outbreaks. Antiviral therapies could reduce the duration and complications of influenza when administered within two days of the onset of illness. Research is necessary for new antiviral therapies that could prevent influenza with cost-effectiveness similar to the influenza vaccine.     

Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir,India, 2010–2012

We estimate the contribution of influenza to hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Kashmir, India. Prospective surveillance for influenza among patients hospitalized with AECOPD was conducted at a tertiary care hospital. Patients had clinical data collected and nasal/throat swabs tested for influenza viruses. Outcomes among patients with and without influenza were compared with logistic regression adjusting for age and underlying conditions. During October 2010–September 2012, 498 patients hospitalized with AECOPD were enrolled, of whom 40 (8%) had received influenza vaccine. Forty (8%) had influenza; influenza virus detection peaked in winter (January–March). Patients with influenza were more likely to die during hospitalization (adjusted OR 3·4, CI 1·0–11·4) than those without.     

Steroid therapy in obstructive airway diseases

Abstract Asthma and chronic obstructive pulmonary disease (COPD) are two common illnesses that cause significant morbidity and mortality. Steroids are widely used in both conditions. They act through steroid or glucocorticoid receptors (GR) causing up or down regulation of protein synthesis resulting in an increase in lipocortin 1 and β₂ adrenergic receptors, and decreased levels and activities of cytokines or cytokine receptors, which reduces the inflammatory process in the airways and decreases bronchial hyperreactivity. Consequently symptoms of airway obstruction are alleviated and lung function is improved. In asthma, steroids have been convincingly shown to be effective in the treatment of both acute exacerbations and chronic condition. In COPD, however, only a subset of patients seem to respond favourably to steroid therapy. Therapeutic trials are therefore recommended before committing to a long-term treatment in order to determine this subset of patients, as no markers of steroid responsiveness can be identified. The inhaled steroids currently available have a good safety profile with significant side effects occurring only occasionally. Such side effects are usually confined to the oropharynx, causing local irritation, candidiasis and dysphonia, which can be easily overcome. Biochemical abnormalities involving bone, adrenal, carbohydrate and lipid profiles have been noted with high doses of inhaled steroids; however, these have no significant clinical effects.     

Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease

Objective

To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection.

Methods

This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty‐one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus‐positive (+) group and AECOPD virus‐negative (?) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum.

Results

A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus? group. However, serum concentrations of interferon‐inducible protein‐10 (IP‐10) and interferon‐gamma (IFN‐γ) in virus+ AECOPD patients were significantly higher than those in the virus? AECOPD, stable COPD and healthy control groups (P < .05).

Conclusion

Viral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP‐10 and IFN‐γ levels might be value to indicate viral infection in AECOPD.

     

Current issues in the management of chronic obstructive pulmonary diseases

Abstract Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, especially among smokers. Many guidelines that have recently been issued emphasize that COPD is not inaccessible to therapeutic measures: although few interventions are capable of affecting its natural history (i.e. smoking cessation and, in patients with severe resting hypoxaemia, oxygen therapy), several others have a demonstrated effect on symptoms and, antitrypsin replacement therapy in emphysema due to alpha₁-antitrypsin deficiency are currently being studied. When there is a marked increase in mucus production, chest physiotherapy using controlled expiration and directed cough maybe useful. Inhaled bronchodilators are frequently effective on dyspnoea, anticholinergic agents being more suitable for continuous symptoms. Rehabilitation, which includes education and psychosocial care, chest physiotherapy, nutritional care and exercise training, also improves quality of life. When there is persistent severe alveolar hypoventilation despite oxygen therapy, long-term mechanical ventilation may be considered. Surgical options in the treatment of emphysema include resection of giant bullae and lung volume reduction surgery. Lung transplantation should be proposed only in patients with end-stage disease, the difficulty here being to define what 'end-stage' means. Finally, all preventive and some therapeutic interventions are likely to be more effective early in the course of the disease. Thus, efforts should be made to detect airways obstruction early in subjects at risk, such as smokers.     

Exacerbation phenotyping in chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are crucial events but causes remain poorly defined. A method to clinically ‘phenotype’ AECOPD have been proposed, and 52 hospitalized chronic obstructive pulmonary disease exacerbations according to underlying aetiology have now been prospectively phenotyped. Multiple exacerbation phenotypes were identified. A subpopulation coinfected with virus and bacteria had a significantly longer length of hospital stay, and this pilot study indicates that exacerbation phenotyping may be advantageous.     

慢性阻塞性肺病继发肺部真菌感染41例临床分析

目的探讨慢性阻塞性肺病(COPD)继发肺部真菌感染的常见原因及对策。方法对41例COPD伴真菌感染病例进行回顾性分析。结果应用抗生素3种以上者23例(56.10%),5种以上者10例(24.39%),29例同时使用了糖皮质激素(70.73%),痰培养的真菌谱为:白念珠菌24例(58.54%),热带念珠菌5例,克柔念珠菌2例,酵母样菌7例,曲霉菌3例。治愈26例(63.41%),好转6例(14.63%),无变化4例(9.76%),死亡5例,病死率12.19%。结论广谱抗生素和糖皮质激素的广泛应用是COPD继发肺部真菌感染的主要原因,及时诊断和治疗可提高其治愈率。     

老年人慢性阻塞性肺病的临床特点分析

目的探讨不同疾病来源的老年人慢性阻塞性肺病（COPD）的临床特点。方法用回顾性调查的方法对206例老年COPD患者进行分析。结果206例老年COPD患者中，122例由慢性支气管炎发展而来，其中31例在COPD的发展过程中合并哮喘，84例由哮喘发展而来。由哮喘发展而来的COPD和COPD合并哮喘的患者其PaCO2平均值较高、容易发生Ⅱ型呼吸衰竭、肺性脑病和气胸，并且合并真菌感染和发生死亡的危险也较大。结论由哮喘而来的COPD和COPD合并哮喘的老年患者，其病情相对较重，并发症多，预后较差。     

Aspergillus infection in chronic obstructive pulmonary diseases

Chronic obstructive pulmonary disease (COPD) is a chronic airway non-specific inflammatory disease characterised by airway obstruction and alveolar destruction. In recent years, due to the extensive use of antibiotics, glucocorticoids, immunosuppressants and other drugs, pulmonary fungal infection in patients with AECOPD, especially aspergillus infection, has gradually increased. The forms of aspergillus infection present in COPD patients include sensitisation, chronic pulmonary aspergillosis (CPA) and invasive pulmonary aspergillosis (IPA). This review will summarise diagnostic and treatment of aspergillus in COPD patients.     

Innate immunity and systemic lupus erythematosus

Innate immunity is the first‐line host defence against pathogens and damaged host cells, and the major cellular components are phagocytes such as monocytes/macrophages, polymorphonuclear cells and dendritic cells. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the loss of tolerance to self‐antigens, the source of which has been suggested to be apoptotic cells. In this article, we will review studies on apoptosis in SLE and discuss the contribution of innate immunity abnormalities in the development of this condition.     

Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains

Background and objective:   Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV.
Methods:   RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-γ induced protein (IP)-10 and IFN-β, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry.
Results:   Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-β that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-β following infection with RV-1B.
Conclusions:   Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-β response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.     

Cigarette smoke augments the expression and responses of toll-like receptor 3 in human macrophages

Background and objective: Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD). Recently, toll‐like receptor 3 (TLR3) was shown to recognize pathogen‐associated molecular patterns, especially viral‐derived double‐stranded RNA, and to be involved in immune responses. However, the effects of cigarette smoke on TLR3 remain unclear. In this study, it was examined whether cigarette smoke affects the expression and responses of TLR3 in human macrophages. Methods: The expression of TLR3 in alveolar macrophages from human lung tissues was analysed by immunohistochemistry, and the correlation of TLR3 expression with smoking history and lung function was evaluated. In addition, the effect of cigarette smoke on the expression and responses of TLR3 in macrophage lineage cells was investigated. Results: TLR3‐positive alveolar macrophage numbers were significantly increased in smokers and COPD patients compared with non‐smoking control subjects, but there was no difference between smokers and COPD patients. TLR3‐positive macrophage numbers were positively correlated with smoking history and inversely correlated with corrected carbon monoxide diffusing capacity, but were not correlated with % predicted forced expiratory volume in 1 s. Furthermore, cigarette smoke extract potentiated the expression of TLR3 in monocyte‐derived macrophages and significantly augmented the release of interleukin‐8, as well as total matrix metalloproteinase‐9 activity, in cells treated with TLR3 ligand. Conclusions: These data suggest that cigarette smoke augments the expression and responses of TLR3 in human macrophages, and this may contribute to neutrophilic airway inflammation and parenchymal destruction in the lungs of smokers and patients with COPD.     

The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.