Paul S. Thomas

Respiratory function in the morbidly obese before and after weight loss.

The morbidly obese are known to have impaired respiratory function. A prospective study of the changes in lung volumes, carbon monoxide transfer, and arterial blood gas tensions was undertaken in 29 morbidly obese patients before and after surgery to induce weight loss. Before surgery the predominant abnormality in respiratory function was a reduction in lung volumes. These increased towards normal predicted values after weight loss, with significant increases in functional residual capacity, residual volume, total lung capacity, and expiratory reserve volume. The increases ranged from 14% for total lung capacity to 54% for expiratory reserve volume. After weight loss had been induced the smokers showed mild hyperinflation and air trapping. Resting arterial blood gas tensions improved, with a rise in arterial oxygen tension from 10.63 to 13.02 kPa and a fall in arterial carbon dioxide tension from 5.20 to 4.64 kPa. There was no correlation between weight loss and the changes in blood gas tensions or lung volumes. Loss of weight in the morbidly obese is thus associated with improved lung function. The effects of smoking on lung function could be detected after weight loss, but were masked before treatment by the opposing effects of obesity on residual volume and functional residual capacity.

Exhaled breath analysis: Novel approach for early detection of lung cancer

Lung cancer is a leading cause of cancer death, with the prognosis adversely affected by late diagnosis. Early diagnosis of lung cancer is desirable, but current evidence does not support the application of screening with techniques such as chest radiography, sputum cytology or computed tomography. Breath analysis, which includes gaseous phase analysis that measures volatile organic compounds using electronic noses, exhaled nitric oxide, and exhaled breath condensate (EBC), has been proposed as a non-invasive and simple technique to investigate neoplastic processes in the airways. EBC can be easily collected by breathing into a cooling system that condenses the water vapour in the breath. EBC has already been demonstrated to be useful in investigating inflammatory and oxidative stress changes in various respiratory conditions as it contains measurable mediators of airway inflammation and oxidative stress markers. Furthermore, EBC has also been shown to be a useful method to monitor severity of diseases such as asthma and to act as a surrogate measure of compliance to medical therapy. Presently, there still remains a relative paucity of lung cancer research involving EBC. However, since EBC is a simple, non-invasive technique that can be easily performed, even in ill patients, it has the potential to be validated for use in screening for the early diagnosis of lung cancer.

Networks for research in primary health care

Editorial by Green and Dovey The evolution of the academic discipline of primary care throughout the world is resulting in more primary care practitioners taking part in research. Primary care has a generalist nature,1 and several research approaches are therefore required to understand the complex interplay between medical and psychosocial factors in the discipline.2 Collaboration is needed between primary care professionals (general practitioners, nurses, health visitors, etc) and a variety of academics with a breadth of expertise.3 In this article we give an overview of primary care research networks. These networks were established as a way to enable diverse practitioners to engage in research. We start by outlining what these networks are and what they do, using examples from the United Kingdom and elsewhere. We then go on to discuss the lessons learnt from UK experience and suggest how these lessons can be built on through better integration with emerging primary care structures. Primary care research networks began to develop in the United Kingdom in the 1960s (box), but until recently there has been little political recognition of their importance. Primary care research was specifically included in the NHS research and development strategy for England and Wales for the first time in 1997. Before then there was no acknowledgement in government of the need to address the low research capacity of primary care. In 1997, the research and development in primary care national working group recommended an investment in care research networks to “achieve an evidence based culture in primary care.”4 #### Summary box Research networks have been established throughout the United Kingdom and internationally to develop research and education in primary health care and implement research evidence These networks can enable multidisciplinary coalitions of researchers to address diverse research agendas Networks may use different organisational approaches including bottom …

Proteomics as a Method for Early Detection of Cancer: A Review of Proteomics, Exhaled Breath Condensate, and Lung Cancer Screening

The study of expressed proteins in neoplasia is undergoing a revolution with the advent of proteomic analysis. Unlike genomic studies where individual changes may have no functional significance, protein expression is closely aligned with cellular activity. This perspective will review proteomics as a method of detecting markers of neoplasia with a particular emphasis on lung cancer and the potential to sample the lung by exhaled breath condensate (EBC). EBC collection is a simple, new, and noninvasive technique, which allows sampling of lower respiratory tract fluid. EBC enables the study of a wide variety of biological markers from low molecular weight mediators to macromolecules, such as proteins, in a range of pulmonary diseases. EBC may be applied to the detection of lung cancer where it could be a tool in early diagnosis. This perspective will explore the potential of applying proteomics to the EBC from lung cancer patients as an example of detecting potential biomarkers of disease and progression.

FTIR Study of the Thermal Degradation of Poly(vinyl Alcohol)

The degradation of poly(vinyl alcohol) was investigated using TG analysis and Fourier transform infrared spectroscopy to determine the effect of atmosphere on the process of degradation. In the spectra, four vibrational modes were identified that characterised the major steps of the degradation process. These were the O-H, C-H, C=O and C=C stretching modes. The mechanism observed for degradation in an inert atmosphere was in accordance with the accepted mechanism of elimination followed by pyrolisation. Evidence of conjugated polyenes, however, was not observed. For the air atmosphere, oxidation in both steps of the degradation process was observed.

Steroid-Resistant Neutrophilic Inflammation in a Mouse Model of an Acute Exacerbation of Asthma

Neutrophilic inflammation in acute exacerbations of asthma tends to be resistant to treatment with glucocorticoids. This may be related to decreased activity and expression of histone deacetylase-2 (HDAC2), which down-regulates expression of proinflammatory genes via recruitment to the glucocorticoid receptor complex. We assessed airway inflammation and response to steroid treatment in a novel mouse model of an acute exacerbation of chronic asthma. Systemically sensitized mice received low-level challenge with aerosolized ovalbumin for 4 weeks, followed by a single moderate-level challenge to induce enhanced inflammation in distal airways. We assessed the effects of pre-treatment with dexamethasone on the accumulation of inflammatory cells in the airways, airway responsiveness to methacholine, expression and enzymatic activity of nuclear proteins including histone acetyl transferase (HAT) and HDAC2, and levels of transcripts for neutrophil chemoattractant and survival cytokines. Dexamethasone suppressed inflammation associated with eosinophil and T-lymphocyte recruitment, but did not prevent neutrophil accumulation or development of airway hyperresponsiveness. Increased activity of HAT was suppressed by steroid treatment, but the marked diminution of HDAC2 activity and increased activity of nuclear factor-kappaB were not reversed. Correspondingly, elevated expression of mRNA for TNF-alpha, granulocyte-macrophage colony-stimulating factor, IL-8, and p21(waf) were also not suppressed by dexamethasone. Levels of lipid peroxidation and protein nitration products were elevated in the acute exacerbation model. We conclude that impaired nuclear recruitment of HDAC2 could be an important mechanism of steroid resistance of the neutrophilic inflammation in exacerbations of asthma. Oxidative stress may contribute to decreased HDAC2 activity.

Asbestos and the lung in the 21st century: an update

The asbestos‐related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s–1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos‐related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.

Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study.

RATIONALE Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown. OBJECTIVES We aimed to evaluate SMRP in an asbestos-exposed cohort. METHODS A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography. MEASUREMENTS AND MAIN RESULTS Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01). CONCLUSIONS This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Biomarkers in pulmonary hypertension

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment. The present article details the more important biomarkers, their potential applications and the evidence supporting their use.

The Interplay between the Effects of Lifetime Asthma, Smoking, and Atopy on Fixed Airflow Obstruction in Middle Age

RATIONALE The contribution by asthma to the development of fixed airflow obstruction (AO) and the nature of its effect combined with active smoking and atopy remain unclear. OBJECTIVES To investigate the prevalence and relative influence of lifetime asthma, active smoking, and atopy on fixed AO in middle age. METHODS The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968 was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick testing, lung volumes, and diffusing capacity measurements. Prevalence estimates were reweighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS Main effects and interactions between lifetime asthma, active smoking, and atopy as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0% (95% confidence interval [CI], 4.5-7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P = 0.042). An interaction (multiplicative effect) was present between asthma and active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but only among those with atopic sensitization. CONCLUSIONS Active smoking and current clinical asthma both contribute substantially to fixed AO in middle age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic individuals with current asthma who smoke to quit.