Low bone mineral density in men with chronic obstructive pulmonary disease

Background

Osteoporosis is common in patients with COPD but the likely multi-factorial causes contributing to this condition (e.g. sex, age, smoking, therapy) mask the potential contribution from elements related to COPD. In order to study osteoporosis and bone mineral density (BMD) related to COPD, we studied a well-defined group of patients and controls.

Methods

BMD, forced expiratory volume in one second (FEV₁), circulating bone biomarkers and biochemistry were determined in 30 clinically stable male ex-smokers with confirmed COPD and 15 age matched "ex-smoker" male controls. None of the patients were on inhaled corticosteroids or received more than one short course of steroids.

Results

Mean (SD) FEV₁% predicted of patients was 64(6)%, the majority having Global Initiative for Chronic Obstructive Lung Disease (GOLD) II airflow obstruction. There were 5/30 patients and 1/15 controls who were osteoporotic, while a further 17 patients and 5 controls were osteopenic. The BMD at the hip was lower in patients than controls, but not at the lumbar spine. Mean values of procollagen type 1 amino-terminal propeptide and osteocalcin, both markers of bone formation, and Type 1 collagen β C-telopeptide, a marker of bone resorption, were similar between patients and controls. However, all bone biomarkers were inversely related to hip BMD in patients (r = -0.51, r = -0.67, r = -0.57, p < 0.05) but did not relate to lumbar spine BMD. 25-OH Vitamin D was lower in patients.

Conclusions

Men with COPD had a greater prevalence of osteoporosis and osteopenia than age matched male controls, with a marked difference in BMD at the hip. Bone biomarkers suggest increased bone turnover.     

Cardiovascular and musculskeletal co-morbidities in patients with alpha 1 antitrypsin deficiency

Background

Determining the presence and extent of co-morbidities is fundamental in assessing patients with chronic respiratory disease, where increased cardiovascular risk, presence of osteoporosis and low muscle mass have been recognised in several disease states. We hypothesised that the systemic consequences are evident in a further group of subjects with COPD due to Alpha-1 Antitrypsin Deficiency (A1ATD), yet are currently under-recognised.

Methods

We studied 19 patients with PiZZ A1ATD COPD and 20 age, sex and smoking matched controls, all subjects free from known cardiovascular disease. They underwent spirometry, haemodynamic measurements including aortic pulse wave velocity (aPWV), an independent predictor or cardiovascular risk, dual energy X-ray absorptiometry to determine body composition and bone mineral density.

Results

The aPWV was greater in patients: 9.9(2.1) m/s than controls: 8.5(1.6) m/s, p = 0.03, despite similar mean arterial pressure (MAP). The strongest predictors of aPWV were age, FEV₁% predicted and MAP (all p < 0.01). Osteoporosis was present in 8/19 patients (2/20 controls) and was previously unsuspected in 7 patients. The fat free mass and bone mineral density were lower in patients than controls (p < 0.001).

Conclusions

Patients with A1ATD related COPD have increased aortic stiffness suggesting increased risk of cardiovascular disease and evidence of occult musculoskeletal changes, all likely to contribute hugely to overall morbidity and mortality.     

Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation

Background

The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR), which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma.

Methods

In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism.

Results

In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses.

Conclusions

Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.     

The MODS method for diagnosis of tuberculosis and multidrug resistant tuberculosis

Patients with active pulmonary tuberculosis (TB) infect 10-15 other persons per year, making diagnosing active TB essential to both curing the patient and preventing new infections. Furthermore, the emergence of multidrug resistant tuberculosis (MDRTB) means that detection of drug resistance is necessary for stopping the spread of drug-resistant strains. The microscopic-observation drug-susceptibility (MODS) assay is a low-cost, low-tech tool for high-performance detection of TB and MDRTB. The MODS assay is based on three principles: 1) mycobacterium tuberculosis (MTB) grows faster in liquid media than on solid media 2) microscopic MTB growth can be detected earlier in liquid media than waiting for the macroscopic appearance of colonies on solid media, and that growth is characteristic of MTB, allowing it to be distinguished from atypical mycobacteria or fungal or bacterial contamination 3) the drugs isoniazid and rifampicin can be incorporated into the MODS assay to allow for simultaneous direct detection of MDRTB, obviating the need for subculture to perform an indirect drug susceptibility test. Competing current diagnostics are hampered by low sensitivity with sputum smear, long delays until diagnosis with solid media culture, prohibitively high cost with existing liquid media culture methods, and the need to do subculture for indirect drug susceptibility testing to detect MDRTB. In contrast, the non-proprietary MODS method has a high sensitivity for TB and MDRTB, is a relatively rapid culture method, provides simultaneous drug susceptibility testing for MDRTB, and is accessible to resource-limited settings at just under $3 for testing for TB and MDRTB.Download video file.^{(243M, mp4)}     

VNTR analysis reveals unexpected genetic diversity within <Emphasis Type="Italic">Mycoplasma agalactiae</Emphasis>, the main causative agent of contagious agalactia

Background  

Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation.     

Home-based versus hospital-based cardiac rehabilitation after myocardial infarction or revascularisation: design and rationale of the Birmingham Rehabilitation Uptake Maximisation Study (BRUM): a randomised controlled trial [ISRCTN72884263]

Background

Cardiac rehabilitation following myocardial infarction reduces subsequent mortality, but uptake and adherence to rehabilitation programmes remains poor, particularly among women, the elderly and ethnic minority groups. Evidence of the effectiveness of home-based cardiac rehabilitation remains limited. This trial evaluates the effectiveness and cost-effectiveness of home-based compared to hospital-based cardiac rehabilitation.

Methods/design

A pragmatic randomised controlled trial of home-based compared with hospital-based cardiac rehabilitation in four hospitals serving a multi-ethnic inner city population in the United Kingdom was designed. The home programme is nurse-facilitated, manual-based using the Heart Manual. The hospital programmes offer comprehensive cardiac rehabilitation in an out-patient setting.

Patients

We will randomise 650 adult, English or Punjabi-speaking patients of low-medium risk following myocardial infarction, coronary angioplasty or coronary artery bypass graft who have been referred for cardiac rehabilitation.

Main outcome measures

Serum cholesterol, smoking cessation, blood pressure, Hospital Anxiety and Depression Score, distance walked on Shuttle walk-test measured at 6, 12 and 24 months. Adherence to the programmes will be estimated using patient self-reports of activity. In-depth interviews with non-attendees and non-adherers will ascertain patient views and the acceptability of the programmes and provide insights about non-attendance and aims to generate a theory of attendance at cardiac rehabilitation. The economic analysis will measure National Health Service costs using resource inputs. Patient costs will be established from the qualitative research, in particular how they affect adherence.

Discussion

More data are needed on the role of home-based versus hospital-based cardiac rehabilitation for patients following myocardial infarction and revascularisation, which would be provided by the Birmingham Rehabilitation Uptake Maximisation Study (BRUM) study and has implications for the clinical management of these patients. A novel feature of this study is the inclusion of non-English Punjabi speakers.     

NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-γ-stimulated immune complex arthritis

In previous studies we have found that FcγRI determines chondrocyte death and matrix metalloproteinase (MMP)-mediated cartilage destruction during IFN-γ-regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to FcγRI leads to the prominent production of oxygen radicals. In the present study we investigated the contribution of NADPH-oxidase-driven oxygen radicals to cartilage destruction by using p47phox^-/- mice lacking a functional NADPH oxidase complex. Induction of a passive ICA in the knee joints of p47phox^-/- mice resulted in a significant elevation of joint inflammation at day 3 when compared with wild-type (WT) controls as studied by histology. However, when IFN-γ was overexpressed by injection of adenoviral IFN-γ in the knee joint before ICA induction, a similar influx of inflammatory cells was found at days 3 and 7, comprising mainly macrophages in both mouse strains. Proteoglycan depletion from the cartilage layers of the knee joints in both groups was similar at days 3 and 7. Aggrecan breakdown in cartilage caused by MMPs was further studied by immunolocalisation of MMP-mediated neoepitopes (VDIPEN). VDIPEN expression in the cartilage layers of arthritic knee joints was markedly lower (between 30 and 60%) in IFN-γ-stimulated arthritic p47phox^-/- mice at day 7 than in WT controls, despite significant upregulation of mRNA levels of various MMPs such as MMP-3, MMP-9, MMP-12 and MMP-13 in synovia and MMP-13 in cartilage layers as measured with quantitative RT-PCR. The latter observation suggests that oxygen radicals are involved in the activation of latent MMPs. Chondrocyte death, determined as the percentage of empty lacunae in articular cartilage, ranged between 20 and 60% at day 3 and between 30 and 80% at day 7 in WT mice, and was completely blocked in p47phox^-/- mice at both time points. FcγRI mRNA expression was significantly lower, and FcγRII and FcγRIII were higher, in p47phox^-/- mice than in controls. NADPH-oxidase-driven oxygen radical production determines chondrocyte death and aggravates MMP-mediated cartilage destruction during IFN-γ-stimulated IC-mediated arthritis. Upregulation of FcγRI by oxygen radicals may contribute to cartilage destruction.