S. P. Man

Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis

Background: Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD. Methods: A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-α (TNF-α), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model. Results: Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-α levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)). Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.

Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis

Background: Individuals with severely impaired lung function have an increased risk of lung cancer. Whether milder reductions in forced expiratory volume in 1 second (FEV1) also increase the risk of lung cancer is controversial. Moreover, there is little consensus on whether men and women have similar risks for lung cancer for similar decreases in FEV1. Methods: A search was conducted of PubMed and EMBASE from January 1966 to January 2005 and studies that examined the relationship between FEV1 and lung cancer were identified. The search was limited to studies that were population based, employed a prospective design, were large in size (⩾5000 participants), and adjusted for cigarette smoking status. Results: Twenty eight abstracts were identified, six of which did not report FEV1 and eight did not adjust for smoking. Included in this report are four studies that reported FEV1 in quintiles. The risk of lung cancer increased with decreasing FEV1. Compared with the highest quintile of FEV1 (>100% of predicted), the lowest quintile of FEV1 (<∼70% of predicted) was associated with a 2.23 fold (95% confidence interval (CI) 1.73 to 2.86) increase in the risk for lung cancer in men and a 3.97 fold increase in women (95% CI 1.93 to 8.25). Even relatively small decrements in FEV1 (∼90% of predicted) increased the risk for lung cancer by 30% in men (95% CI 1.05 to 1.62) and 2.64 fold in women (95% CI 1.30 to 5.31). Conclusion: Reduced FEV1 is strongly associated with lung cancer. Even a relatively modest reduction in FEV1 is a significant predictor of lung cancer, especially among women.

Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis

BackgroundRecent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men. Whether female adult smokers are biologically more susceptible to COPD is unknown. This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.MethodsA systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.ResultsOf the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants). There was heterogeneity in gender-related results across the studies. However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers. Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008). Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).ConclusionAs female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers. Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.

Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium.

CT in COPD: just a pretty picture or really worth a thousand words (or dollars)?

We like pretty pictures and, in pulmonary medicine, we use computed axial tomography (CT) to generate pretty pictures to help us diagnose and manage patients with respiratory complaints. In 2007 more than 10 million chest CT scans were performed across the USA, representing an astounding 11 000% increase in the CT rate since 1980.1 CT scans rely on ionising radiation to generate images, and recent estimates suggest that CT scans may be responsible for 24% of the total ‘background’ radiation to which the population is exposed in a given year.2 Thankfully, there are several large-scale efforts to reduce the radiation exposure related to CT scans and to mitigate the health risks imposed by ionising radiation.3 What is not being adequately addressed is the issue of economic costs (and benefits) of CT scans. CT scans are expensive for patients and to the healthcare system, with prices ranging from

Elevated Plasma Lipopolysaccharide Levels Are Associated With More Frequent Hospitalizations In Adult Cystic Fibrosis Patients

500 to

Unilateral Emphysema Model In Rats

1500 per scan.4 Recently, the cost-effectiveness ratio of lung cancer screening with CT scans was reported to be

Budesonide/Formoterol Attenuates Cardiovascular Dysfunction Related To Acute Lung Injury In Mice

2.3 million dollars per quality-adjusted life saved,5 providing us with a sobering reminder that these ‘pretty pictures’ are not without significant costs. Chronic obstructive pulmonary disease (COPD) is a condition that lends itself to anatomical medical imaging. For practical reasons, COPD is largely defined based on spirometric criteria. However, there is general discontent with this approach because spirometric measurements are relatively insensitive and correlate only very loosely with histological abnormalities or with patient symptoms or …